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2,100 | 23,303,652 | In conclusion , non-removable off-loading devices regardless of type , are more likely to result in ulcer healing than removable off-loading devices , presumably because patient compliance with off-loading is facilitated | Effective off-loading is considered to be an important part of the successful clinical management of diabetic foot ulcers .
The aim of this systematic review is to investigate the safety and effectiveness of different off-loading devices for the treatment of diabetic foot ulcers . | OBJECTIVE A limited number of clinical trials have shown that the total contact cast ( TCC ) is an effective treatment in neuropathic , noninfected , and nonischemic foot ulcers . In this prospect i ve data collection study , we assessed outcome and complications of TCC treatment in neuropathic patients with and without peripheral arterial disease ( PAD ) or ( superficial ) infection . RESEARCH DESIGN AND METHODS Ninety-eight consecutive patients selected for casting were followed until healing ; all had polyneuropathy , 44 % had PAD , and 29 % had infection . Primary outcomes were percentage healed with a cast , time to heal , and number of complications . RESULTS Ninety percent of all nonischemic ulcers without infection and 87 % with infection healed in the cast ( NS ) . In patients with PAD but without critical limb ischemia , 69 % of the ulcers without infection and 36 % with infection healed ( P < 0.01 ) . In multivariate analyses , PAD , infection , and heel ulcers were associated with a lower percentage healed ( all P < 0.05 ) . Median duration of cast treatment was 34 days . New ulcers , all superficial , developed in 9 % and preulcerative lesions in 28 % of the patients ; these skin lesions healed in the cast within a maximum of 13 days . CONCLUSIONS In comparison to pure neuropathic ulcers , ulcers with moderate ischemia or infection can be treated effectively with casting . However , when both PAD and infection are present or the patient has a heel ulcer , outcome is poor and alternative strategies should be sought . The high rate of preulcerative lesions stresses the importance of close monitoring during TCC treatment OBJECTIVE The purpose of this study was to compare the effectiveness of a removable cast walker ( RCW ) rendered irremovable ( iTCC ) with the total contact cast ( TCC ) in the treatment of diabetic neuropathic plantar foot ulcers . RESEARCH DESIGN AND METHODS In a prospect i ve , r and omized , controlled trial , 41 consecutive diabetic patients with chronic , nonischemic , neuropathic plantar foot ulcers were r and omly assigned to one of two groups : a RCW rendered irremovable by wrapping it with a single layer of fiberglass casting material ( i.e. , an iTCC ) or a st and ard TCC . Primary outcome measures were the proportion of patients with ulcers that healed at < /=12 weeks , healing rates , complication rates , cast placement/removal times , and costs . RESULTS The proportions of patients with ulcers that healed within 12 weeks in the iTCC and TCC groups were 80 and 74 % , respectively ( 94 and 93 % , respectively , when patients who were lost to follow-up were excluded ) . Survival analysis ( healing rates ) was statistically equivalent in the two groups , as were complication rates , but with a trend toward benefit in the iTCC group . The iTCC took significantly less time to place and remove than the TCC with 39 % and 36 % reductions , respectively . There was also an overall lower cost associated with the use of the iTCC compared with the TCC . CONCLUSIONS The iTCC may be equally efficacious , faster to place , easier to use , and less expensive than the TCC in the treatment of diabetic plantar neuropathic foot ulcers Neuropathic plantar ulcers are classical lesions secondary to diabetic polyneuropathy ( 1,2 ) . The worldwide gold st and ard treatment is the nonremovable off-loading cast ( 3–5 ) . However , the device is not widely used due to concerns related to risk factors of the off-loading cast ( i.e. , joint rigidity , additional ulcer formation beneath the cast , and infection of the ulcer enclosed in the cast ) . Our group recently demonstrated that it is possible to reduce the risk of side effects reported in literature by constructing the off-loading cast using fiberglass b and ages of different rigidity . Considering the device ’s scarce application because of the side effects , we conducted a controlled , r and omized , prospect i ve trial to evaluate the safety and efficacy of a removable pneumatic cast walker in comparison with a nonremovable fiberglass off-loading cast . Between January 2005 and October 2005 , 60 consecutive diabetic patients with neuropathic plantar ulcers were seen and r and omly assigned to two groups : group A , using an Aircast Pneumatic Walker ( XP Diabetic Walker ) ; and group B , using the fiberglass off-loading cast . All participants had peripheral neuropathy , as highlighted by insensitivity to 10 g monofilament and vibration perception threshold measured by biothesiometer at malleolus of at least 25 volts , and presented OBJECTIVE —This study was design ed to test the safety , effectiveness , and costs of off-loading with a novel , off-the-shelf irremovable device in the management of diabetic foot ulceration ( DFU ) . RESEARCH DESIGN AND METHODS —We prospect ively evaluated off-loading of neuropathic plantar ulcers in 40 diabetic out patients attending our diabetic foot clinic and compared healing rates at the 12-week follow-up , number and severity of adverse events , healing time , costs and applicability of the device , and patients ’ satisfaction between those r and omly assigned to total contact casting ( TCC ; group A ) or to the Optima Diab walker ( group B ) . Deep or infected ulcers were excluded . RESULTS —No difference between groups A and B was observed in healing rates at 12 weeks ( 95 vs. 85 % ) , healing time ( 6.5 ± 4.4 vs. 6.7 ± 3.4 weeks ) , and number of adverse events ( six versus four ) . Treatment was significantly less expensive in group B , which showed a mean reduction of costs of 78 % compared with group A ( P < 0.001 ) . Practicability was more favorable in group B , with a reduction of 77 and 58 % of the time required for application and removal of the devices , respectively ( P < 0.001 ) . Patients ’ satisfaction with the treatment was higher in group B ( P < 0.01 ) . CONCLUSIONS —The Optima Diab walker is as safe and effective as TCC in the management of DFU , but its lower costs and better applicability may be of help in spreading the practice of off-loading among the centers that manage the diabetic foot OBJECTIVE To compare the efficacy , safety , and compliance of a nonremovable fiberglass cast boot and off-loading shoes in the treatment of diabetic plantar ulcers . RESEARCH DESIGN AND METHODS Patients ( n = 93 ) with noninfected , nonischemic plantar ulcers were included in this prospect i ve nonr and omized study . Treatment used a nonremovable fiberglass cast boot for longer st and ing and deeper ulcers ( n = 42 ) and a half shoe or heel-relief shoe for other ulcers ( n = 51 ) . We evaluated off-loading therapy , compliance , and complications in both groups . RESULTS The healing rate was significantly higher with the cast boot than with the off-loading shoe ( 81 vs. 70 % , P = 0.017 ) , with healing times of 68.6 + /- 35.1 vs. 134.2 + /- 133.0 days , respectively , and hazard ratio 1.68 ( 95 % CI 1.04 - 2.70 ) ; complete compliance with treatment was 98 vs. 10 % ( P = 0.001 ) , respectively . Secondary osteomyelitis developed in 3 patients in the cast boot group and 13 patients in the off-loading shoe group ( P = 0.026 ) . CONCLUSIONS A nonremovable fiberglass cast boot was effective in healing diabetic plantar ulcers and in decreasing the risk of secondary osteomyelitis . The cast boot forced compliance with off-loading , thus promoting healing OBJECTIVE To evaluate the efficacy of a removable cast walker compared with that of a nonremovable fiberglass off-bearing cast in the treatment of diabetic plantar foot ulcer . RESEARCH DESIGN AND METHODS Forty-five adult diabetic patients with nonischemic , noninfected neuropathic plantar ulcer were r and omly assigned for treatment with a nonremovable fiberglass off-bearing cast ( total contact cast [ TCC ] group ) or walker cast ( Stabil-D group ) . Treatment duration was 90 days . Percent reduction in ulcer surface area and total healing rates were evaluated after treatment . RESULTS A total of 48 patients were screened ; however , 2 patients in the TCC group and 1 patient in the Stabil-D group did not complete the study and were considered dropouts . There were no significant differences in demographic and clinic characteristics of the 45 patients completing the study . Ulcer surface decreased from 1.41 to 0.21 cm2 ( P < 0.001 ) in the TCC group and from 2.18 to 0.45 cm2 ( P < 0.001 ) in the Stabil-D group , with no significant differences between groups ( P = 0.722 ) . Seventeen patients ( 73.9 % ) in the TCC group and 16 patients ( 72.7 % ) in the Stabil-D group achieved healing ( P = 0.794 ) . Average healing time was 35.3 ± 3.1 and 39.7 ± 4.2 days in the TCC and Stabil-D group , respectively ( P = 0.708 ) . CONCLUSIONS The Stabil-D cast walker , although removable , was equivalent in efficacy to the TCC in terms of ulcer size reduction and total healing rate . The easier use of Stabil-D may help increase the use of off-loading devices in the management of plantar neuropathic diabetic foot ulcers The objective of this study was to compare the effectiveness of irremovable total-contact casts ( TCC ) and custom-made temporary footwear ( CTF ) to heal neuropathic foot ulcerations in individuals with diabetes . In this prospect i ve clinical trial , 43 patients with plantar ulcer Grade 1 or 2 ( Wagner scale ) were r and omized to one of two off-loading modalities : TCC or CTF . Outcomes assessed were wound surface area reduction ( cm2 ) and time to wound healing ( days ) at 2 , 4 , 8 and 16 weeks . To evaluate safety , possible side effects were recorded at each follow-up visit . The results showed no significant difference in wound surface area reduction ( adjusted for baseline wound surface ) at 2 , 4 , 8 or 16 weeks ( adjusted mean difference 0.10 cm2 ; 95 % CI −0.92−0.72 at 16 weeks ) . At 16 weeks , 12 patients had a completely healed ulcer , 6 per group . The median time to healing was shorter for the patients using a cast ( 52 vs. 90 days , p = 0.26 ) . Five patients with TCC and two with CTF developed device-related complications . It was concluded that : ( i ) the rate of wound healing is not significantly different for patients treated with CTF or TCC . The difference in wound surface area was small and not significant at any time during follow-up ; and ( ii ) the difference in healing time ( 38 days ) may have attained statistical significance if the numbers in these sub-groups ( 2 × 6 ) had been higher . Since there appears to be little difference in effectiveness between both off-loading modalities , further investigation into the benefits of CTF is warranted OBJECTIVE The purpose of this study was to evaluate the effectiveness of a removable cast walker ( RCW ) and an " instant " total contact cast ( iTCC ) in healing neuropathic diabetic foot ulcerations . RESEARCH DESIGN AND METHODS We r and omly assigned 50 patients with University of Texas grade 1A diabetic foot ulcerations into one of two off-loading treatment groups : an RCW or the same RCW wrapped with a cohesive b and age ( iTCC ) so patients could not easily remove the device . Subjects were evaluated weekly for 12 weeks or until wound healing . RESULTS An intent-to-treat analysis showed that a higher proportion of patients had ulcers that were healed at 12 weeks in the iTCC group than in the RCW group ( 82.6 vs. 51.9 % , P = 0.02 , odds ratio 1.8 [ 95 % CI 1.1 - 2.9 ] ) . Of the patients with ulcers that healed , those treated with an iTCC healed significantly sooner ( 41.6 + /- 18.7 vs. 58.0 + /- 15.2 days , P = 0.02 ) . CONCLUSIONS Modification of a st and ard RCW to increase patient adherence to pressure off-loading may increase both the proportion of ulcers that heal and the rate of healing of diabetic neuropathic wounds OBJECTIVE To compare the effectiveness of total contact casts , commercially available therapeutic shoes , and removable walking casts to reduce mean peak plantar foot pressures at the site of neuropathic ulcerations in diabetic subjects . RESEARCH DESIGN AND METHODS We compared the reduction in peak plantar pressures at ulcer sites under the great toe ( n = 5 ) , first metatarsal ( n = 10 ) , and second through fifth metatarsals ( n = 10 ) using six treatments : total contact casts ( TCCs ) , DH Pressure Relief Walkers ( DH ) , Aircast Pneumatic Walkers , Three D Dura-Steppers ( 3D ) , CAM Walkers , and P.W. Minor Xtra Depth shoes . A rubber sole canvas oxford was used to establish baseline pressure values . The canvas oxford could be viewed as a worse-case scenario for this patient population . With the EMED Pedar in-shoe pressure measurement system , data for 40 steps were collected for each treatment . We used Tukey 's Studentized Range Test for simultaneous multiple comparisons to compare treatments . RESULTS DH Pressure Relief Walkers reduced plantar pressures significantly better than other commercially available treatments for ulcers under the first metatarsal , second through fifth metatarsals , and great toe ( P < 0.05 ) . There was not a significant difference in mean peak plantar pressures between TCCs and DHs at any of the forefoot ulcer sites . CONCLUSIONS DH Pressure Relief Walkers were as effective as total contact casts to reduce foot pressures at ulcer sites and may be an effective practical addition in the treatment of foot ulcers OBJECTIVE To evaluate the recurrence of foot ulcers as well as the cumulative amputation and mortality rates in diabetic patients with previous foot ulcers . DESIGN A prospect i ve study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer with a median follow-up of 4 years . SETTING A multidisciplinary foot-care team . POPULATION Five-hundred- and -fifty-eight consecutive diabetic patients with foot ulcers treated between 1 July 1983 and 31 December 1990 were followed to final outcome . Out of these patients , 468 healed either primarily ( n = 345 ) or after minor or major amputations ( n = 123 ) and 90 died before healing had occurred . Those 468 patients who healed were included in this prospect i ve study from the time of healing . MAIN OUTCOME MEASURES Patients were followed according to a st and ardized protocol with registration of foot lesions , amputation , morbidity and mortality . Clinical examination was performed twice yearly . RESULTS After 1 , 3 and 5 years of observation 34 % , 61 % and 70 % of the patients , respectively , had developed a new foot ulcer . The recurrence rate of foot lesions was slightly higher among patients who previously had had an amputation ( P < 0.05 , P < 0.01 and non-significant , respectively ) . Among patients with previous primary healing the cumulative amputation rates were 3 % , 10 % and 12 % after 1 , 3 and 5 years of follow-up compared with 13 % , 35 % and 48 % among those who previously healed after amputation , irrespective of previous amputation level ( P < 0.001 at all time-points ) . All amputations except three were initiated by a foot ulcer deteriorating to deep infection or progressive gangrene . The long-term survival ratio was lower among patients healed after previous amputation ( 80 % , 59 % , 27 % ) compared with patients with previously primary healing ( 92 % , 73 % , 58 % ) after 1 , 3 and 5 years of observation , respectively ( P < 0.001 , P < 0.01 and P < 0.001 respectively ) . The mortality rate was twice as high among primarily healed and four times as high among patients with amputation compared to an age- and sex-matched Swedish population . CONCLUSION These findings stress the need for life-long surveillance of the diabetic foot at risk and the necessity of preventive foot care among diabetic patients with previous foot lesions , and particularly among those who had had a previous amputation AIMS The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of diabetic foot ulcers , but knowledge of its effects on wound healing is sparse . The objective of this study was to evaluate the effects of felted foam on wound healing in diabetic foot ulcers compared with a st and ard method of plantar pressure relief . MATERIAL S AND METHODS A total of 54 Type 1 or Type 2 diabetic patients with neuropathic diabetic foot ulcers were evaluated in this prospect i ve r and omized controlled study . Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing . The patients were consecutively enrolled in the study ; 24 patients were r and omized to the felted foam therapy , and 30 patients were r and omized to conventional therapy . RESULTS In the felted foam group , the initial average wound area was 102.3 + /- 45.3 mm2 ( mean + /- sd ) , and 5.4 + /- 3.1 mm2 after 10 weeks with an average healing time of 75 days [ 95 % confidence interval ( CI ) 67 - 84 ] . In the conventional therapy group , the initial average wound area was 112.5 + /- 50.8 mm2 , and 10.6 + /- 4.2 mm2 after 10 weeks with an average healing time of 85 days ( 95 % CI 79 - 92 ) ( P = 0.03 ) . The mean wound radius decreased by 0.48 mm ( 95 % CI 0.42 - 0.56 ) per week in the felted foam group and by 0.39 mm ( 95 % CI 0.35 - 0.42 ) per week in the conventional group ( P = 0.005 ) . CONCLUSIONS The felted foam technique appears to be at least as effective as conventional plantar ulcer treatment . It may be a useful alternative in treating neuropathic foot ulceration , especially in patients who are not able to avoid weight-bearing reliably OBJECTIVE To compare the effectiveness of total-contact casts ( TCCs ) , removable cast walkers ( RCWs ) , and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes . RESEARCH DESIGN AND METHODS In this prospect i ve clinical trial , 63 patients with superficial noninfected , nonischemic diabetic plantar foot ulcers were r and omized to one of three off-loading modalities : TCC , half-shoe , or RCW . Outcomes were assessed at wound healing or at 12 weeks , whichever came first . Primary outcome measures included proportion of complete wound healing at 12 weeks and activity ( defined as steps per day ) . RESULTS The proportions of healing for patients treated with TCC , RCW , and half-shoe were 89.5 , 65.0 , and 58.3 % , respectively . A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities ( 89.5 vs. 61.4 % , P = 0.026 , odds ratio 5.4 , 95 % CI 1.1 - 26.1 ) . There was also a significant difference in survival distribution ( time to healing ) between patients treated with a TCC and both an RCW ( P = 0.033 ) and half-shoe ( P = 0.012 ) . Patients were significantly less active in the TCC ( 600.1 + /- 320.0 daily steps ) compared with the half-shoe ( 1,461.8 + /- 1,452.3 daily steps , P = 0.04 ) . There was no significant difference in the average number of steps between the TCC and the RCW ( 767.6 + /- 563.3 daily steps , P = 0.67 ) or the RCW and the half-shoe ( P = 0.15 ) . CONCLUSIONS The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities , the RCW and the half-shoe Retrospective and prospect i ve studies have shown that elevated plantar pressure is a causative factor in the development of many plantar ulcers in diabetic patients and that ulceration is often a precursor of lower-extremity amputation . Herein , we review the evidence that relieving areas of elevated plantar pressure ( off-loading ) can prevent and heal plantar ulceration . There is no consensus in the literature concerning the role of off-loading through footwear in the primary or secondary prevention of ulcers . This is likely due to the diversity of intervention and control conditions tested , the lack of information about off-loading efficacy of the footwear used , and the absence of a target pressure threshold for off-loading . Uncomplicated plantar ulcers should heal in 6 to 8 weeks with adequate off-loading . Total-contact casts and other nonremovable devices are most effective because they eliminate the problem of nonadherence to recommendations for using a removable device . Conventional or st and ard therapeutic footwear is not effective in ulcer healing . Recent US and European surveys show that there is a large discrepancy between guidelines and clinical practice in off-loading diabetic foot ulcers . Many clinics continue to use methods that are known to be ineffective or that have not been proved to be effective while ignoring methods that have demonstrated efficacy . A variety of strategies are proposed to address this situation , notably the adoption and implementation of recently established international guidelines , which are evidence based and specific , by professional societies in the United States and Europe . Such an approach would improve the often poor current expectations for healing diabetic plantar ulcers BACKGROUND Elevated plantar loading has been implicated in the etiology of plantar ulceration in individuals with diabetes mellitus and peripheral neuropathy . Total contact casts and cast walker boots are common off-loading strategies to facilitate ulcer healing and prevent re-ulceration . The purpose of this study was to compare off-loading capabilities of these strategies with respect to plantar loading during barefoot walking . METHODS Twenty-three individuals with diabetes , peripheral neuropathy , and plantar ulceration were r and omly assigned to total contact cast ( n=11 ) or removable cast walker boot ( n=12 ) . Each subject underwent plantar loading assessment walking barefoot and wearing the off-loading device . Analysis of covariance was used to compare loading patterns in the off-loading devices for the whole foot , hindfoot , midfoot , and forefoot while accounting for walking speed and barefoot loading . FINDINGS For the foot as a whole , there were no differences in off-loading between the two techniques . Subjects wearing cast walker boots had greater reductions in forefoot peak pressure , pressure-time integral , maximum force , and force-time integral with respect to barefoot walking . Healing times were similar between groups , but a greater proportion of ulcers healed in total contact casting compared to cast walker boots . INTERPRETATION In subjects with diabetes , peripheral neuropathy , and plantar ulceration , cast walker boots provided greater load reduction in the forefoot , the most frequent site of diabetic ulceration , though a greater proportion of subjects wearing total contact casts experienced ulcer healing . Taken together , the less effective ulcer healing in cast walker boots despite superior forefoot off-loading suggests an important role for patient compliance in ulcer healing |
2,101 | 16,856,053 | The substantial heterogeneity between trials was not explained by potassium dose , quality of trials or baseline blood pressure .
This systematic review found no statistically significant effect of potassium supplementation on blood pressure . | BACKGROUND Epidemiological evidence on the effects of potassium on blood pressure is inconsistent .
OBJECTIVES To evaluate the effects of potassium supplementation on health outcomes and blood pressure in people with elevated blood pressure . | The Trial of Antihypertensive Interventions and Management is a multicenter r and omized trial design ed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension ( diastolic blood pressure 90 - 100 mm Hg ) . Eight hundred and seventy-eight participants at 110 - 160 % of ideal weight were r and omly allocated to nine drug/diet treatment groups receiving either a placebo , chlorthalidone ( 25 mg ) , or atenolol ( 50 mg ) , combined with a usual , a weight loss , or a low sodium/high potassium diet The primary outcome was diastolic blood pressure change from baseline to 6 months . Seven hundred and eighty-seven participants had follow-up data . The mean baseline diastolic blood pressure was 93.8 mm Hg ; 55.9 % of the participants were male , and the weight loss diet group lost an average of 4.7 kg . Multiple comparisons were accounted for in the analysis . A significantly greater lowering of diastolic blood pressure ( 12.4 mm Hg ) was achieved in the atenolol group compared with either the low sodium/high potassium diet group ( 7.9 mm Hg , p=0.001 ) or weight loss group ( 8.8 mm Hg , p=0.006 ) . Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering ( 15.1 mm Hg ) when compared with the diuretic alone ( 10.8 mm Hg , p=0.002 ) , but adding a low sodium/high potassium diet ( 12.2 mm Hg , p=0.029 ) did not In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration , drugs outperform diet , and weight loss is beneficial , especially with diuretics OBJECTIVE To determine whether an increase in dietary potassium intake from natural foods reduces the need for antihypertensive medication in patients with essential hypertension . DESIGN R and omized , controlled trial with 1-year follow-up . SETTING Hypertension outpatient clinic of a university hospital . PATIENTS Fifty-four patients with well-controlled hypertension , 47 of whom completed 1 year of follow-up . INTERVENTION Patients were r and omly assigned to one of two groups and were given dietary advice aim ed at selectively increasing potassium intake ( group 1 ) or at keeping their customary diet unchanged ( group 2 ) . During a 1-year follow-up period , drug therapy was reduced in stepwise fashion , according to a fixed protocol , provided that blood pressure remained below 160/95 mm Hg . MAIN RESULTS Potassium intake was checked monthly by referring to 3-day food records and by measuring 24-hour urinary potassium excretion . Potassium intake increased in group 1 but did not change in group 2 ( P less than 0.001 ) . No change was observed in either urinary sodium excretion or in body weight . After 1 year , the average drug consumption ( number of pills per day ) relative to that at baseline was 24 % in group 1 ( 95 % Cl , 15 % to 32 % ) and 60 % in group 2 ( Cl , 44 % to 76 % ) ( P less than 0.001 ) . By the end of the study , blood pressure could be controlled using less than 50 % of the initial therapy in 81 % of the patients in group 1 ( Cl , 66 % to 96 % ) compared with 29 % of the patients in group 2 ( Cl , 10 % to 48 % ) ( P = 0.001 ) . Patients in group 1 ended the study with a lower number of reported symptoms compared with patients in the control group ( P less than 0.001 ) . CONCLUSION Increasing the dietary potassium intake from natural foods is a feasible and effective measure to reduce antihypertensive drug treatment Phase I of the Trials of Hypertension Prevention ( TOHP ) was a r and omized , multicenter investigation that included double-blind , placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults ( 10.5 % blacks and 31 % women ) aged 30 to 54 years with high-normal diastolic blood pressure ( DBP ) ( 80 to 89 mm Hg ) . Very high compliance ( 94 to 96 % by pill counts ) with daily doses of 1 g of calcium ( carbonate ) , 360 mg of magnesium ( diglycine ) , or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women . Overall , neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months . Analyses stratified by baseline intakes of calcium , magnesium , sodium , or initial blood pressures also showed no effect of supplementation . These analyses suggested that calcium supplementation may have result ed in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels , urinary sodium levels , or lower body mass index . However , overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP . The subgroup analyses , useful to formulate hypotheses , raise the possibility of a benefit to white women , which requires testing in future trials Thirty-three patients with hypertension receiving drug treatment that included a potassium losing diuretic were r and omly allocated to 64 mmol of potassium ( 14 patients ) or to no additional potassium supplementation ( 19 patients ) . Potassium was administered as slow release potassium chloride . After 3 months , blood pressure fell by 5/1 mm Hg in the patients who received the supplements and by 7/4 mm Hg in those who did not receive them . The falls in pressure were not significantly different and the 90 % confidence limits for the effect of supplementation on diastolic pressure were : a fall of 2 mm Hg and a rise of 11 mm Hg , thus excluding an important hypotensive effect in these patients . Conversely , plasma creatinine fell by 11 % in the supplement group compared with a 6 % rise in the control group ( P less than 0.05 ) . Potassium supplementation , either by pharmacological preparations or by dietary manipulation , may prove to be desirable in patients on a potassium losing diuretic but should not be expected to lower blood pressure in such patients Potassium chloride ( KCl ) salt ( 65 mmol ) daily reduced BP from 153/104 to 146/101 mmHg in 32 hypertensive black females during a 6-week placebo controlled crossover study . The fall in BP was independent of the order of r and omization and was significant for systolic ( SBP ; P less than 0.01 ) and diastolic ( DBP ; P less than 0.05 ) pressure after 4 weeks . Analysis of the 95 % confidence intervals in this and in five other studies , two of which were reported as showing no beneficial effect , suggests that potassium supplementation does lower BP , but that the change is small and within the confidence levels of all six trials . Thus , apparent discrepancies in the literature are not genuine statistically The blood pressure responses of 19 mildly hypertensive ( diastolic blood pressure 90–104 mmHg ) individuals to treatment with either 1200 mg of elemental calcium supplementation or placebo were assessed weekly in a 6-month r and omized , double-blind , placebo-controlled crossover study . Both groups showed a decrease in blood pressure ( calcium treated : 6 ± 12 mmHg systolic , 7 ± 7 mmHg diastolic ; and placebo controlled : 9 ± 14 mmHg systolic , 9 ± 8 mmHg diastolic ) . Differences between the two groups were not significant ( P > 0.1 ) . There were no adverse effects to either treatment . This study does not support the hypothesis that dietary calcium supplementation is more effective than placebo in reducing blood pressure in mildly hypertensive individuals In a double-blind , placebo-controlled trial with 58 normotensive female students , the effect of oral-calcium supplementation ( 1500 mg Ca++/day for 6 wk ) on diastolic and systolic blood pressure was studied while students were consuming a low-calcium diet ( 500 mg Ca++/day ) by restricting the intake of dairy products . Results show that , in both the calcium- and placebo-supplemented groups , blood pressure values decreased slightly and no effect of oral-calcium supplementation on blood pressure could be demonstrated . In addition , at baseline neither systolic nor diastolic blood pressure correlated with habitual calcium intake . Diastolic but not systolic blood pressure correlated significantly with body mass index ( r = 0.31 , p = 0.01 ) . It is concluded that oral-calcium supplementation for 6 wk does not influence blood pressure in young , healthy normotensive females consuming low-calcium diet BACKGROUND Total body potassium ( TBK ) is an index of fat-free mass . Data describing changes in TBK in African American , Asian , or Hispanic population s have not been reported . OBJECTIVE The aim was to investigate possible sex and racial differences in TBK in adults over an age range of 70 y. DESIGN The study used longitudinal and cross-sectional data collected in a body-composition unit from 973 men and 1368 women of African American , Asian , white , and Hispanic race-ethnicity . R and om coefficient models in which baseline weight and height were taken into account were applied to estimate sex-specific changes in TBK among the 4 racial-ethnic groups . RESULTS The ages of 30 and 31 y were identified for women and men , respectively , as the cutoffs after which TBK began to decline . Both sexes had similar racial-ethnic patterns for expected mean TBK at the age cutoffs : African Americans had the highest value , followed by whites , Hispanics , and Asians . After the age cutoffs , the decline in TBK differed by race and sex . In women , African Americans showed the most rapid decline , whereas Asians had the lowest . In men , Hispanics had the most rapid decline in TBK , followed by African Americans , whites , and Asians . CONCLUSION Significant sex and racial differences exist in the rate of change in TBK with age . Further studies are needed to explore the associations of declining TBK with health risks OBJECTIVE To determine the effect of potassium supplementation on blood pressure in African Americans consuming a low-potassium diet . DESIGN R and omized , double-blind , placebo-controlled trial with two parallel arms . SETTING Community-based research site . PARTICIPANTS Eighty-seven healthy African Americans aged 27 to 65 years with a systolic blood pressure between 100 and 159 mm Hg and a diastolic blood pressure between 70 and 94 mm Hg . INTERVENTION During the 21-day intervention period , all participants were provided with a low-potassium diet ( 32 to 35 mmol/d ) . In addition to this diet , they were r and omly assigned to receive either potassium supplements ( 80 mmol/d ) or placebo . MAIN OUTCOME MEASURE Change in blood pressure in the potassium vs the placebo group , based on a total of nine blood pressure readings at three visits . Blood pressures were taken before and during the intervention by means of r and om-zero sphygmomanometry . RESULTS At baseline , the placebo and potassium groups were similar for mean blood pressure ( 127/78 vs 125/77 mm Hg ) , 24-hour urinary potassium excretion ( 50 vs 44 mmol ) , and all other variables measured ( all P > .05 ) . During the intervention , the net difference in 24-hour urinary potassium excretion between groups was 70 mmol . Compared with the placebo group , the potassium supplementation group experienced a net decline in systolic blood pressure of 6.9 mm Hg ( 95 % confidence interval , -9.3 to -4.4 mm Hg ; P < .001 ) and a decline in diastolic blood pressure of 2.5 mm Hg ( 95 % confidence interval , -4.3 to -0.8 mm Hg ; P = .004 ) . Simultaneous adjustment for differences in baseline characteristics only strengthened these estimates . CONCLUSIONS Potassium supplementation reduces blood pressure substantially in African Americans consuming a diet low in potassium . Increased potassium intake may play an important role in reducing blood pressure in this population at high risk for hypertension Epidemiological and experimental data suggest blood pressure-lowering effects of dietary potassium . A r and omized , double-blind clinical trial was used to assess blood pressure response to orally administered potassium , 120 mEq/day , and to placebo in 101 adults with mild hypertension . Blood pressure was measured with a r and om-zero sphygmomanometer every 2 weeks of this 8-week trial . Systolic blood pressure in the potassium-treated group decreased by 6.4 + /- 13.7 ( SD ) mm Hg ( p less than or equal to 0.025 ) compared with 0.11 + /- 13.0 mm Hg in the placebo-treated group ( p = 0.96 ) . Diastolic blood pressure in the potassium-treated group decreased by 4.1 + /- 8.3 mm Hg ( p less than or equal to 0.05 ) compared with a 1.6 + /- 6.5 mm Hg decrease in placebo-treated subjects ( p = 0.09 ) . Baseline blood pressure of potassium-treated subjects was unexpectedly higher than that of controls . After correcting for baseline variation , blood pressure still decreased 3.4/1.8 mm Hg more in potassium recipients than in placebo recipients ( p = 0.14 and 0.24 , respectively ) . Blood pressure decreased by 19/13 mm Hg in five blacks taking potassium versus a 1/0 mm Hg increase in seven blacks taking placebo . Compliance with the potassium regimen was 91.5 % by pill count ; only one subject discontinued treatment because of side effects . In conclusion , 120 mEq/day of microencapsulated potassium chloride was well tolerated in adults with mild hypertension . An antihypertensive effect of potassium can not be ruled out despite the fact that there was no statistically significant difference between potassium-treated and placebo-treated subjects after adjustment for differences in baseline blood pressure . ( ABSTRACT TRUNCATED AT 250 WORDS To determine the effects of potassium on blood pressure and factors affecting blood pressure , we conducted a r and omized , placebo controlled trial of a potassium chloride-based substitute for table salt in 23 patients with mild to moderate essential hypertension . In addition , the effects of potassium chloride on sodium balance were studied in 10 normal subjects . Potassium loading with 100 mmol/day over five days in these normal subjects caused a cumulative negative sodium balance of 138 + /- 35 mmol , similar in degree to that achieved by severe dietary sodium restriction . However , two weeks of potassium treatment ( 100 mmol/day ) in patients with essential hypertension did not lower blood pressure ( BP ) either in the supine or upright positions ( potassium treatment : mean BP 108 + /- 3 lying and 113 + /- 3 mmHg st and ing ; placebo treatment : mean BP 109 + /- 3 lying and 115 + /- 3 mmHg st and ing ) . Patients found it difficult to tolerate the potassium-based salt substitute in the dose given . We conclude that it is premature to recommend an increase in potassium chloride intake as treatment for raised blood pressure A r and omized , double-blind , placebo-controlled crossover trial of oral calcium supplementation was carried out in 18 patients with uncomplicated essential hypertension . After 15 weeks of oral calcium supplementation , 1 g/day , of the patients ' habitual diet , the only blood pressure change ( compared with the results of placebo treatment ) was in the average st and ing systolic blood pressure , which was significantly reduced ( -8.6 mm Hg ; p less than 0.01 ) . The 24-hour urinary calcium excretion and the total serum calcium concentration increased significantly during calcium supplementation ( p less than 0.05 ) , indicating good compliance with the treatment . The individual blood pressure changes with high calcium intake were found to be inversely related to basal 24-hour urinary calcium excretion ( r = -0.69 , p less than 0.001 for st and ing systolic pressure ; r = -0.55 , p less than 0.002 for st and ing diastolic pressure ) . This correlation was independent of age , basal blood pressure , serum calcium concentration , basal 24-hour urinary sodium excretion , and body weight changes during the trial . In particular , a subgroup of six patients , who had a basal 24-hour urinary calcium excretion higher than the mean + 2 SD of a reference healthy population previously described , showed a substantial average blood pressure fall at variance with the other patients in the study . These results do not support the usefulness of an oral calcium supplement in the majority of subjects with mild essential hypertension ; however , they suggest that a group of patients with a previously reported abnormality of calcium metabolism may be responsive to this therapeutic measure Objectives : To determine the effects of potassium chloride 60 mmol/day supplementation on clinic and 24-h ambulatory blood pressure values in elderly untreated hypertensive patients Design : A double-blind r and omized placebo-controlled crossover study lasting 8 weeks , following a 4-week run-in period Setting : Outpatient clinic in a district general hospital Patients : Eighteen untreated elderly hypertensive patients ( mean age 75 years , range 66—79 ) with a systolic blood pressure of ≥160mmHg and /or a diastolic blood pressure of ≥95mmHg were recruited from the clinics of local general practitioners and from the current hospital outpatient department . Patients had not received any antihypertensive medication for at least 4 weeks before entry into the study Interventions : Before entry into the study , the daily dietary electrolyte intake of each individual was established and this was maintained during the run-in and intervention periods . Following a 4-week run-in period patients received potassium supplements or matching placebo , each for 4 weeks Main outcome measures : The within-patient changes in clinic and 24-h ambulatory blood pressures at the end of each intervention period . Results : After 4 weeks potassium supplementation compared with placebo there was a significant fall in supine clinic blood pressure , st and ing and 24-h ambulatory systolic blood pressure . There was no significant change in clinic st and ing diastolic blood pressure , 24-h ambulatory diastolic blood pressure or pulse rate . Plasma renin activity increased and body weight fell after potassium supplementation . Twenty-four-hour urinary potassium rose significantly , whereas urinary sodium excretion was unchanged Conclusions : A 60-mmol daily supplement of potassium chloride reduces clinic and 24-h ambulatory blood pressure in elderly hypertensive We conducted a r and omized , double-blind , placebo-controlled trial of oral potassium chloride supplementation ( 60 mmol/d ) in 353 men and women with an initial average diastolic blood pressure between 80 and 89 mm Hg . In the active ( n = 178 ) compared to the placebo ( n = 175 ) treatment group , the urinary potassium level was significantly ( p < 0.001 ) increased by an average of 44.0 and 42.3 mmol/24 h following 3 and 6 months of therapy , respectively . Compared to placebo , active treatment was associated with a small ( mean = 1.8 mm Hg ) but significant ( p = 0.04 ) reduction in diastolic blood pressure following 3 months of therapy . Following 6 months , however , this apparent treatment effect had virtually disappeared ( mean reduction in diastolic blood pressure = 0.3 mm Hg ) . There was no significant effect of potassium supplementation on systolic blood pressure at either follow-up visit . There was a significant , independent , dose-response relationship between change in both 24-hour urinary potassium excretion and urinary sodium-potassium ratio and the corresponding change in diastolic blood pressure ( -1.49 mm Hg for the highest versus the lowest quartile of change in urinary potassium excretion BACKGROUND AND OBJECTIVE : We have previously demonstrated an antiobesity effect of dietary Ca ; this is largely mediated by Ca suppression of calcitriol levels , result ing in reduced adipocyte intracellular Ca2 + and , consequently , a coordinated increase in lipid utilization and decrease in lipogenesis . Notably , dairy Ca is markedly more effective than other Ca sources . DESIGN : Obese subjects were placed on balanced deficit ( −500 kcal/day ) diets and r and omized to control ( 400–500 mg Ca/day ; n=16 ) or yogurt ( 1100 mg Ca/day ; n=18 ) treatments for 12 weeks . Dietary macronutrients and fiber were held constant at the US average . MEASUREMENTS : Body weight , body fat and fat distribution ( by dual-energy X-ray absorptiometry ) , blood pressure and circulating lipids were measured at baseline and after 12 weeks of intervention . RESULTS : Fat loss was markedly increased on the yogurt diet ( −4.43±0.47 vs −2.75±0.73 kg in yogurt and control groups ; P<0.005 ) while lean tissue loss was reduced by 31 % on the yogurt diet . Trunk fat loss was augmented by 81 % on the yogurt vs control diet ( P<0.001 ) , and this was reflected in a markedly greater reduction in waist circumference ( −3.99±0.48 vs −0.58±1.04 cm , P<0.001 ) . Further , the fraction of fat lost from the trunk was higher on the yogurt diet vs control ( P<0.005 ) . CONCLUSION : Isocaloric substitution of yogurt for other foods significantly augments fat loss and reduces central adiposity during energy restriction Phase II of the Trials of Hypertension Prevention is a multicenter , r and omized , controlled trial design ed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure . The 2 x 2 factorial study design includes weight loss alone , restricted sodium intake alone , the combination of weight loss and sodium restriction , and a control group . Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months , which exceeded the sample size goal of 2250 . Among r and omized participants , 21 % were minorities and 34 % were women . Overall , direct mail generated the most r and omized participants ( 73 % ) , followed by community screening ( 12 % ) and media advertisement ( 11 % ) . Referrals from community health care providers yielded few participants . Prescreening improved overall efficiency and reduced costs . Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger , single , male , smokers , and less educated Forty-seven patients with mild hypertension and 48 normotensive patients entered a blinded , parallel study in which they received a placebo , 10 mmol/day calcium carbonate ( CaCO3 ) , or 20 mmol/day CaCO3 . There were no significant differences in blood pressure changes among the groups . In the hypertensive group and in patients with the highest blood pressure there were individual falls in systolic pressure , particularly in the group receiving 10 mmol daily CaCO3 . In the hypertensive group the changes were : with placebo , −3±2/− 2±2 mm Hg ; with CaCO3 ( 10 mmol ) , −7±3/− 2±2 mm Hg ; and with CaCO3 ( 20 mmol ) , −2±3/l±2 mm Hg . No change was significant , and no pressure changes of patients taking CaCO3 differed significantly from changes of patients taking placebo . Ten of 33 patients taking placebo , 11 of 31 taking 10 mmol/ day CaCO3 , and nine of 31 taking 20 mmol/day CaCO3 were classified as responders from their systolic blood pressure fall . These response rates did not differ . Eight patients had falls of systolic blood pressure greater than 15 mm Hg . Five were on 10 mmol/day CaCO3 and three on 20 mmol/day CaCO3 . This response was significantly different from that with placebo . Univariate analyses failed to reveal any predictive dietary or biochemical parameter . After 3 months of not taking CaCO3 , 12 patients classified as responders , including six of the eight with a fall of 15 mm Hg or more , were rer and omized to placebo or to 20 mmol/day CaCO3 . In the rechallenge , responses to CaCO3 and placebo were similar , neither causing a significant pressure fall . Calcium carbonate did not reduce blood pressure . The apparent response hi a few patients was not verified by rechallenge . The present study does not support calcium supplementation as a useful nonpharmacological measure for reducing elevated blood pressure The effect of oral calcium supplementation ( 1000 mg/day ) on hypertension was studied in 57 borderline and mild-to-moderate hypertensive patients in a r and omized , double-blind , placebo-controlled study for 14 weeks . Twenty-five patients from the above groups ( 11 from the calcium-treated group and 14 from the placebo group ) were studied in a crossover fashion for 14 more weeks . The high calcium intake lowered systolic blood pressure by 17 mm Hg ( P < .01 ) , and diastolic blood pressure by 11 mm Hg ( P < .01 ) . Fifty percent of the calcium-treated patients showed a significant antihypertensive effect and were termed calcium responders . In the crossover study , serum sodium was lower after taking calcium than after placebo intake ( P < .05 ) . Pretreatment plasma free calcium content of the calcium-responsive patients was significantly lower ( P < .05 ) than in the calcium nonresponsive patients , and was highly significantly increased ( P < .01 ) after administering calcium . The result showed that oral calcium supplementation can lower blood pressure in a significant fraction of essential hypertensive subjects , and that the free calcium level in plasma may help identify calcium-responsive individuals . While the mechanism by which increased calcium intake lowers blood pressure in hypertension is still undetermined , these data support an underlying relationship between hypertension and calcium and possibly sodium metabolism Over the past few years , several trials on the effect of oral calcium supplementation on blood pressure have been undertaken both in normal subjects and in patients with high blood pressure . Of these , 15 r and omized , controlled studies were review ed : 10 included patients with high blood pressure , three studied normal subjects , and two used a low-calcium diet for comparison . The 15 studies review ed investigated a total of nearly 400 peoples . No significant evidence for a supine blood pressure-lowering effect of oral calcium supplementation was found in the trials as a whole or in those trials carried out in hypertensives only . However , a small effect on st and ing blood pressure was detected . Our study indicates that the overall effect of oral calcium on blood pressure , if any , is very small and confined to st and ing blood pressure , it is , therefore , inappropriate to recommend oral calcium supplementation for the treatment of essential hypertension To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure ( BP ) of 140 to 159 mm Hg and /or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension ( DASH ) study . Participants were fed a control diet for a 3-week period and were then r and omized to receive for 8 weeks either the control diet ; a diet rich in fruits and vegetables , but otherwise similar to control ; or a combination diet rich in fruits , vegetables , and low-fat dairy products , including whole grains , fish , poultry , and nuts , and reduced in fats , red meats , sweets , and sugar-containing beverages . Sodium intake and body weight were held constant throughout the study . The combination diet significantly reduced systolic BP ( -11.4 mm Hg , P < .001 ) and diastolic BP ( -5.5 mm Hg , P < .001 ) . The fruits- and -vegetables diet also significantly reduced systolic BP ( -7.2 mm Hg , P < .001 ) and diastolic BP ( -2.8 mm Hg , P = .013 ) . The combination diet produced significantly greater BP effects ( P < .05 ) than the fruits- and -vegetables diet . Blood pressure changes were evident within 2 weeks of starting the intervention feeding . After the 8-week intervention period , 70 % of participants eating the combination diet had a normal BP ( systolic BP < 140 and diastolic BP < 90 mm Hg ) compared with 45 % on the fruits- and -vegetables diet and 23 % on the control diet . In patients with hypertension , the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension Forty young subjects , aged 18 to 28 years , with mildly elevated blood pressure participated in a double-blind r and omized three-period crossover study of the effect of sodium restriction with and without potassium supplementation on blood pressure . Dietary sodium intake was restricted for 18 weeks in which the patients received in r and om sequence ' slow-sodium ' ( 90 mmol/day ) , ' slow-potassium ' ( 72 mmol/day ) , and placebo tablets , each for 6 weeks . Mean urinary sodium excretion was 129 mmol/24 h in the slow-sodium period , 57 mmol/24 h during placebo , and 69 mmol/24 h during slow-potassium . Mean supine systolic blood pressure in the sixth week of the slow-potassium period was 3.3 mmHg lower than that at the end of the slow-sodium period ( P less than 0.05 ) . There was no significant difference in systolic or diastolic blood pressure between the placebo and the slow-sodium periods . The fall in systolic blood pressure in the low sodium/high potassium period was accompanied by a fall in cardiac index of 0.4 l/min per m2 body surface area ( BSA ) ( P = 0.03 ) . Our observations suggest a small hypotensive effect of moderate sodium restriction combined with high potassium intake in young hypertensive subjects . Sodium restriction alone has little effect on blood pressure in this group . The combination of a low sodium/high potassium diet may lower blood pressure by affecting cardiac output . Reducing the dietary sodium : potassium ratio may therefore be useful in the management of early primary hypertension It is generally accepted that a significant restriction in sodium intake can lower blood pressure in hypertensive patients and more recently it has also been suggested that a high potassium intake can exert an antihypertensive effect . We have therefore , conducted a double-blind , r and omized , cross-over study to evaluate the antihypertensive efficacy of the combination of a modest dietary sodium restriction and a high potassium intake in hypertensive patients of mild and moderate degrees . During the modest sodium ( 100 mmol/day)/high potassium ( 130 mmol/day ) diet the blood pressure was significantly reduced ( -17/-6 mmHg ) when compared to the normal diet ( 160 mmol Na/day and 80 mmol K/day ) . The blood pressure reduction did not interfere with hemodynamic and humoral responses to dynamic exercise . The modest reduction in sodium intake and increase in potassium content in the diet was well tolerated by the patients A 15 week r and omised double blind placebo controlled trial of oral potassium supplements ( 48 mmol daily ) was conducted in 37 patients who had mildly increased blood pressure and a normal dietary intake of sodium . After a two month run in and a one week baseline period the patients were r and omly assigned to receive either potassium supplements ( n = 18 ) or placebo ( n = 19 ) . By the third week of treatment blood pressure in the actively treated group had decreased significantly compared with that in the placebo group , though the decrease reached its maximum after 15 weeks . Urinary potassium excretion increased significantly in the group who received potassium supplements , but no significant changes were found in plasma sodium and potassium concentrations or in urinary sodium excretion . In a subgroup of 13 patients who underwent a further nine weeks of treatment with oral potassium supplements at half of the previous dose ( 24 mmol daily ) their blood pressure , at the end of this second study period , was still significantly lower compared with their baseline value but not with that of the placebo group . These results show that moderate oral potassium supplements are associated with a long term reduction in blood pressure in patients who have mild hypertension We evaluated the effect of oral calcium supplementation on blood pressure , calcium metabolism , and insulin resistance in essential hypertension . After receiving a st and ard diet with 500 mg of calcium per day during a 4-week period , 20 nondiabetic , essential hypertensive patients were r and omized in a double-blind fashion to receive oral calcium supplementation ( 1500 mg of calcium per day ) or placebo for 8 weeks . At the end of the 4-week period of low-calcium diet and after the 8-week period of intervention , we measured blood pressure ( by both office and 24-hour ambulatory blood pressure monitoring ) , calcium-regulating hormones [ urinary hydroxyproline and serum osteocalcin , parathormone , and 1,25(OH)2-vitamin D3 ] , intraplatelet free calcium concentration , fasting plasma glucose and insulin levels , and the insulin-sensitivity index ( euglycemic-hyperinsulinemic clamp ) . Compared with patients maintained at low calcium intake , essential hypertensive patients under oral calcium supplementation significantly reduced serum osteocalcin ( from 22.2 + /- 1.9 to 17.9 + /- 2.0 micrograms/L ; P = .0015 ) , parathormone ( from 4.20 + /- 0.38 to 3.30 + /- 0.36 pmol/L ; P = .0003 ) , and 1,25(OH)2-vitamin D3 ( from 98.0 + /- 11.0 to 61.6 + /- 5.7 pmol/L ; P = .0062 ) . Likewise , we found a significant reduction in intraplatelet free calcium concentration ( from 35.9 + /- 1.2 to 26.5 + /- 0.8 nmol/L ; P = .0005 ) and fasting plasma insulin levels ( from 71.8 + /- 5.9 to 64.6 + /- 6.2 pmol/L ; P = .05 ) and a significant increase in the insulin-sensitivity index ( from 2.89 + /- 0.77 to 4.00 + /- 0.95 mg.kg-1.min-1 ; P = .0007 ) . None of these parameters were significantly modified in patients maintained at low calcium intake . Office and 24-hour mean values of systolic and diastolic blood pressure did not change after 8 weeks of oral calcium supplementation or placebo An increase in magnesium intake has been suggested to lower blood pressure ( BP ) . However , the results of clinical studies are inconsistent . We studied the effects of magnesium supplementation on office , home , and ambulatory BPs in patients with essential hypertension . Sixty untreated or treated patients ( 34 men and 26 women , aged 33 to 74 years ) with office BP > 140/90 mm Hg were assigned to an 8-week magnesium supplementation period or an 8-week control period in a r and omized crossover design . The subjects were given 20 mmol/d magnesium in the form of magnesium oxide during the intervention period . In the control period , office , home , and average 24-hour BPs ( mean+/-SE ) were 148.6+/-1.6/90.0+/-0.9 , 136.4+/-1.3/86.8+/-0.9 , and 133.7+/-1.3/81.0+/-0.8 mmHg , respectively . All of these BPs were significantly lower in the magnesium supplementation period than in the control period , although the differences were small ( office , 3.7+/-1.3/1.7+/-0.7 mmHg ; home , 2.0+/-0.8/1.4+/-0.6 mmHg ; 24-hour , 2.5+/-1.0/1.4+/-0.6 mm Hg ) . Serum concentration and urinary excretion of magnesium increased significantly with magnesium supplementation . Changes in 24-hour systolic and diastolic BPs were correlated negatively with baseline BP or changes in serum magnesium concentration . These results indicate that magnesium supplementation lowers BP in hypertensive subjects and this effect is greater in subjects with higher BP . Our study supports the usefulness of increasing magnesium intake as a lifestyle modification in the management of hypertension , although its antihypertensive effect may be small This study was undertaken to determine if calcium carbonate supplementation could reduce blood pressure in an older population that had mildly increased pressure and if blood pressure reduction could be maintained over the course of 1 year with continued supplementation . Volunteers 50 to 80 years of age were included if their systolic blood pressure ( when not taking antihypertensive medication ) was consistently greater than or equal to 140 mm Hg or if diastolic blood pressure was greater than or equal to 90 mm Hg during a 4-week baseline period . Each subject then received placebo tablets for 4 weeks followed by 1 g calcium carbonate tablets for 12 weeks in a single-blinded fashion . If either systolic or diastolic blood pressure was reduced by at least 5 mm Hg with calcium supplementation as compared to placebo , calcium supplementation was continued for 36 weeks . A 25 % sub sample of subjects completed a 12-week placebo run-out . Supine and st and ing systolic and diastolic blood pressure did not change significantly with 12 weeks of calcium carbonate as compared to placebo ( P = NS ) . In 42 of 103 subjects with at least a 5 mm Hg initial decrease in blood pressure who were continued on calcium supplementation , blood pressure did not change significantly through 36 weeks . In the 12 subjects who completed the placebo run-out period , systolic pressures increased significantly ( P less than .05 ) and did not differ from baseline ( P = NS ) . There is no evidence in this study for general use of calcium supplementation to reduce blood pressure in an older population . ( ABSTRACT TRUNCATED AT 250 WORDS Forty-four normotensive females , who were selected on the basis of lower prevailing potassium intake , participated in a two-period crossover study to assess the effects of potassium supplementation on blood pressure . They were r and omly allocated to one of two groups who took either 80 mmol/day of KCl ( Slow-K , Ciba Geigy ) , or matching placebo , for the first of two 4-week treatment periods . The treatments were reversed during the second 4-week period . Despite significant increases in both urinary and plasma potassium no consistent fall in blood pressure was seen during 80 mmol/day potassium intake Objective To study the effects of a high calcium intake in hypertensive patients by blood pressure monitoring . Design In a r and omized crossover study , patients were assigned to an 8-week calcium supplementation period and an 8-week control period . The subjects were given 25 mmol/day ( 1 g/day ) of calcium as calcium carbonate during the intervention period . Setting A hypertension clinic in a tertiary teaching hospital . Patients Sixty untreated or treated hypertensive patients ( 35 men and 25 women , mean age 58 years ) with office systolic/diastolic blood pressure ≥ 140/90 mmHg . Main outcome measures Office blood pressure , home blood pressure ( last 7 days ) , and ambulatory 24 h blood pressure ( every 30 min using TM-2421 ) . Results The serum calcium concentration and urinary calcium excretion increased significantly with calcium supplementation . Office , home and 24 h blood pressure were lower in the calcium period than in the control period , although the differences were small ( mean ± SEM office blood pressure : 1.2 ± 1.2/1.1 ± 0.7 mmHg ; home blood pressure : 1.9 ± 0.7/1.3 ± 0.6 mmHg ; 24 h blood pressure : 1.2 ± 0.8/0.9 ± 0.5 mmHg , ) , and significant only for home systolic and diastolic blood pressures . The difference in home systolic blood pressure was inversely correlated with the level of home blood pressure in the control period and with the difference in urinary calcium . The difference in 24 h systolic blood pressure was positively correlated with the control level of urinary calcium . Age , sex , antihypertensive medication , drinking habit , sodium intake or order of treatment did not significantly influence the effects of calcium supplementation . Conclusions An increase in calcium intake tends to lower office , home and ambulatory blood pressure in hypertensive patients . However , the antihypertensive effect is too small to support the general application of a high calcium intake in the treatment of hypertension As sub studies of the Medical Research Council 's trials of treatment of mild hypertension and of hypertension in the elderly , two studies were carried out comparing the effects of different doses of two diuretics on blood pressure , concentrations of some biochemical variables , and the incidence of subjective adverse reactions . In one study , in which 484 patients with mild hypertension participated , daily doses of bendrofluazide 5 mg and 10 mg , with and without oral potassium supplements , were compared . In the second , involving 701 elderly patients with hypertension , daily doses of hydrochlorothiazide 25 mg together with amiloride 2.5 mg were compared with hydrochlorothiazide 50 mg together with amiloride 5 mg . The mean ( + /- SD ) duration s of treatment were 35 + /- 17 months in the first study and 10 + /- 7 months in the second . Neither study showed any significant difference in blood pressure response to the two doses of diuretic , whereas biochemical changes and the reported incidence of subjective adverse reactions were dose-related . In the first study , potassium supplementation with potassium chloride 16.8 or 33.6 mmol did not have a significant effect on the fall in serum potassium level , which was only slightly reduced , and did not have any significant effect on the antihypertensive effect of either dose of bendrofluazide An increase in potassium ( K ) intake may lower blood pressure ( BP ) , but inconsistent results have been obtained in clinical trials . We studied the effects of K supplementation in hypertensive patients with monitoring of home and ambulatory BP . Fifty-five patients with essential hypertension ( 26 men , 29 women , 36 - 77 years old ) participated in this study . A 4-week K supplementation period and 4-week control period were assigned in a r and omized crossover manner . During the K period , the subjects were given 64 mmol/day of K as slow-release KCl tablets . Office , home , and 24-h BP , as well as serum and urinary electrolytes , were measured at the end of each period . In the control period , office , home , and 24-h BP were 151 + /- 2/88 + /- 1 ( mean + /- SE ) , 138 + /- 1/83 + /- 1 , and 137 + /- 1/81 + /- 1 mm Hg , respectively . Serum K increased from 4.15 + /- 0.04 to 4.42 + /- 0.05 mmol/L , and urinary K increased from 54 + /- 2 to 96 + /- 3 mmol/day with the K supplementation . Office , home , and 24-h BP were significantly lower in the K period than in the control period , although the differences were small ( 2.7 + /- 1.1/1.4 + /- 0.6 , 3.6 + /- 0.9/1.7 + /- 0.5 , 3.4 + /- 1.0/1.2 + /- 0.5 mm Hg , respectively ) . Changes in home and 24-h systolic BP with K supplementation were highly significant ( P < .001 ) , compared with office BP ( P < .05 ) . The change in 24-h systolic BP was correlated negatively with baseline BP and urinary Na/K ratio , and positively with baseline urinary K excretion . The changes in daytime and nighttime BP were comparable . These results indicate that increasing K intake lowers BP in hypertensive subjects , especially in those with higher BP and lower K intake . Our study supports the usefulness of K supplementation in the treatment of hypertension , although its antihypertensive effect may be small To determine whether moderate restriction of dietary sodium content or supplementation of potassium intake reduces blood-pressure in patients with mild essential hypertension , twelve patients were put on three different diets -- a control diet ( 180 mmol sodium/day ) , a sodium restricted diet ( 80 mmol/day ) . Each diet was taken for at least 4 weeks and the sequence of the regimens was r and omised . At the completion of each regimen intra-arterial pressure was recorded continuously , and vasoactive hormones were measured hourly , for 24 h , under st and ardised conditions , in hospital . Compared with the control diet , sodium restriction was associated with lower blood-pressure readings in seven patients , higher levels in five , and an overall reduction in mean pressures of only 4.0/3.0 mm Hg ( not significant ) . Individual differences in blood-pressure between these two diets correlated closely with concomitant differences in plasma renin activity ( r = 0.75 ) . Potassium supplementation also result ed in variable changes in arterial pressure , and the mean difference in pressure recordings ( 0.1/0.8 mm Hg ) was insignificant . The results show that moderate restriction of sodium intake or supplementation of dietary potassium has variable effects on arterial pressure in individuals with mild essential hypertension , and that overall the blood-pressure changes induced are very small . Responsiveness of the renin-angiotensin system may limit the fall in blood-pressure induced by sodium restriction Epidemiologic surveys , experimental studies in animals , and clinical trials in young and middle-aged patients with hypertension indicate that dietary potassium lowers blood pressure . The mechanism of the antihypertensive effect is not well defined . Variations in serum potassium within the physiologic range may directly affect vascular smooth muscle tone . Potassium may also influence the regulation of blood pressure through effects on sodium h and ling , aldosterone secretion , the renin/angiotensin system , renal kallikrein , eicosanoids , and atrial natriuretic peptide . This study was undertaken to confirm the blood pressure-lowering effect of potassium in older patients and to determine the mechanism of the antihypertensive effect . Twenty-two patients greater than or equal to 60 yr of age were admitted to a Clinical Research Unit for 8 days after a 2-wk period free of antihypertensive medication . Patients were placed on an isocaloric diet containing 200 mmol/day of Na+ , 70 mmol/day of K+ , and 500 mg/day of Ca2 + and were treated in a r and omized , double-blinded manner with either potassium chloride ( 120 mmol/day ) or placebo . After 4 days , patients were crossed over to the alternate treatment . Systolic blood pressure decreased 8.6 mm Hg ( 95 % confidence interval -14.6 , -2.6 ) , and diastolic blood pressure decreased 4.0 mm Hg ( -6.9 , -1.0 ) during potassium chloride supplementation . There was no significant change in blood pressure during treatment with placebo . Serum K+ was 3.9 + /- 0.1 mmol/L after 3 days of placebo and 4.3 + /- 0.1 after 4 days of potassium chloride ( P less than 0.002 ) . Urinary sodium excretion averaged 192 + /- 11 mmol/day after placebo and 221 + /- 8 after potassium treatment ( P less than 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Previous studies suggest that oral calcium supply reduces blood pressure in patients with mild to moderate hypertension . The aim of this study was to determine whether oral calcium supply reduces blood pressure in patients undergoing haemodialysis . The study was r and omized , double-blind , and placebo controlled . Eleven patients received two grams of calcium per day and 12 patients received placebo . Three patients ( one from the calcium group and two from the placebo group ) dropped out within the first month . The groups were comparable at inclusion regarding blood pressure , weight , and serum values . Blood pressure measurements were auscultatory with a mercury manometer and diastolic blood pressure was measured as Korotkoff phase V. At inclusion a significant positive correlation between serum phosphate and blood pressure was found . After a study period of six months a significant reduction in diastolic blood pressure was found between the two groups ( p < 0.05 ) , but no difference was found in systolic blood pressure . The reduction in diastolic blood pressure was 6.9 mmHg of the pretreatment level in the calcium group . In conclusion , the treatment of secondary hyperparathyroidism with oral calcium gives good benefits in the regulation of diastolic blood pressure . A well controlled phosphate homeostasis may also be of importance for the control of blood pressure in haemodialysis patients To determine the early effect of potassium loading on blood pressure regulatory mechanisms , the effect of 4 days ' supplementation with 80 mmol/day KCl on blood pressure and vasodilator hormone release was examined using a double-blind crossover design in normotensive women with a baseline potassium excretion of 51.8 + /- 2.7 mmol/day . Systolic blood pressure fell 1.7 + /- 0.6 mm Hg , ( P less than .01 ) in association with a mean increase in sodium excretion of 14.7 + /- 4.5 mmol/day and an increase in urine volume of 122.6 + /- 57.0 mL/day . There was a small but significant fall in plasma atrial natriuretic peptide ( ANP ) over the 4 days of potassium supplementation , while significant increases were seen in the levels of plasma potassium ( P less than .01 ) and aldosterone ( P less than .01 ) . After 4 days of KCl , urinary 6-keto-PGF1 alpha was significantly elevated and correlated positively with urinary sodium excretion . Plasma renin activity was unchanged . The results suggest that increased vasodilator prostanoid synthesis and a mild natriuresis may contribute to the transient fall in systolic blood pressure . The increase in aldosterone and reduction in ANP probably represent homeostatic responses to this natriuresis , and could account for the failure of potassium supplementation to induce a long-term reduction in blood pressure in other studies in normotensive subjects In several trials , a blood pressure lowering effect of potassium chloride could be demonstrated . However , it is not known if other potassium salts are also effective . In a r and omized cross-over trial , 12 patients with essential hypertension were treated for 8 weeks with placebo and 120 mmol potassium per day . Potassium was given together with 50 % citrate and 50 % bicarbonate as anions . Urinary potassium excretion rose from 61.8 + /- 8.1 to 166.7 + /- 21.2 mmol/24 hours during potassium supplementation . However , blood pressure and heart rate remained unchanged when compared to placebo . Non-chloride potassium salts may not be effective in lowering blood pressure in essential hypertension . Since potassium rich foods like fruits and vegetables contain potassium mostly as non-chloride salts , it appears to be premature to recommend a high dietary potassium intake as a mean to treat elevated blood pressure ABSTRACT : The effects of 800 mg of elemental calcium per day ( calcium carbonate or calcium citrate ) on blood pressure were compared with a placebo in a controlled r and omized , crossover , double-blinded trail involving 26 patients with uncomplicated primary hypertension . Each patient took two of the three forms of therapy orally for 8-week intervals with a 2-week washout period in between . St and ing mean blood pressure rose an average of 5.7 mm Hg on placebo , rose an average of 0.5 mm Hg on calcium carbonate , and fell an average of 2.2 mm Hg on calcium citrate . Changes in sitting mean pressures averaged + 1.9 mm Hg on placebo , −0.4 mm Hg on calcium carbonate , and −0.4 mm Hg on calcium citrate . Some patients had a fall , others had a rise in blood pressure on each form of calcium . Similarly , inconsistent responses were noted among the nine patients who took both forms of calcium . Neither initial nor post-treatment biochemical measures nor patient characteristics were predictive of the blood pressure response . Combinations of various measures and characteristics analyzed by the multiple regression technique explained only 30 % of the overall variability in blood pressure . Therefore , until ways can be found to predict the response , calcium supplements should not be routinely prescribed for the treatment of hypertension and , if given for any indication , blood pressure should be A controlled trial of the effect of low versus high calcium intake on blood pressure was performed in 15 patients with mild essential hypertension ( supine blood pressure after a 1-month run-in period : 145.7 + /- 2.6/97.8 + /- 0.9 mmHg , mean + /- s.e.m . ) . After a 1-week baseline period on a st and ard calcium intake ( 900 mg/day , obtained by giving a 500-mg calcium tablet daily , in addition to a 400-mg calcium diet ) , the patients were r and omly entered into a double-blind crossover study of 4-week low calcium intake ( 400 mg calcium diet plus two placebo tablets/day ) and 4-week high calcium intake ( 1400 mg/day : 400-mg calcium diet plus two 500-mg calcium tablets/day ) . Compliance with the diets appeared to be satisfactory , based on the results of food record analysis . No significant blood pressure change was observed at the end of the low-compared to the high-calcium regimen . Serum ionized calcium was slightly , but not significantly lower , while 24-h urinary calcium excretion was significantly reduced during the low-calcium diet . No difference was found in urinary sodium and potassium excretion between the two study periods . We conclude that moderate modifications of oral calcium intake are not associated with changes in blood pressure within the time span of this study Phase II of the Trials of Hypertension Prevention ( TOHP ) is a multicenter , r and omized trial sponsored by the National Heart , Lung , and Blood Institute design ed to test whether weight loss alone , sodium reduction alone , or the combination of weight loss and sodium reduction will decrease diastolic ( DBP ) and systolic blood pressure ( SBP ) as well as the incidence of hypertension ( DBP > or = 90 mm Hg , SBP > or = 140 mm Hg , and /or use of antihypertensive medications ) in subjects with high-normal DBP ( 83 to 89 mm Hg ) and SBP less than 140 mm Hg at entry . These interventions were chosen for longer-term testing with end points including hypertension prevention as well as blood pressure ( BP ) change based on their demonstrated short-term efficacy in reducing BP in phase I of TOHP . The phase II study population is comprised of 2382 participants ( 1566 men and 816 women ) who are 110 to 165 % of desirable body weight , allocated at r and om to the four treatment arms using a 2 x 2 factorial design . The trial has 80 % power to detect an overall treatment effect on DBP of 1.2 mm Hg for weight loss or sodium reduction and a difference of 1.6 mm Hg between the combined intervention and placebo groups . BP observers are blinded to participant treatment assignments . Participants will be followed for 3 to 4 years . This trial may have important public policy implication s concerning the ability of life-style modifications to reduce BP and prevent the development of hypertension over the long term , thereby avoiding the need for drug therapy which while effective is costly and may have side effects Two-hundred- and -twelve untreated subjects ( mean age 52.3 + /- 0.8 years ; 181 males and 31 females ) with a diastolic blood pressure between 90 and 100 mmHg were recruited to the study . Subjects were seen fortnightly and , after 4 pre-diet visits , were r and omized into a normal diet group ( A , 55 subjects ) , a high-potassium diet group ( B , 52 subjects receiving greater than 100 mmol K+/day ) a reduced-sodium diet group ( C , 52 subjects receiving 50 - 75 mmol Na+/day ) or a high-potassium and low-sodium diet group ( D , 53 subjects receiving same Na+ and K+ as groups B and C ) . Two-hundred subjects completed the diet phase of 12 weeks . Urine sodium fell to 86 + /- 7 mmol/day in group C and 73 + /- 6 mmol/day in group D , while daily potassium excretion rose to 96 + /- 5 mmol in group B and 87 + /- 4 mmol in group C. Systolic and diastolic blood pressure fell by 3.8 + /- 1.0 and 1.6 + /- 0.6 mmHg respectively in the normal diet group . The falls in systolic and diastolic blood pressures ( mmHg ) in the diet phase were 7.7 + /- 1.1 and 4.7 + /- 0.7 ( B ) , 8.9 + /- 1.0 and 5.8 + /- 0.6 ( C ) and 7.9 + /- 0.9 and 4.2 + /- 0.7 ( D ) . These falls were all greater than those in the control group on an intention-to-treat analysis ( P less than 0.005 ) but did not differ from each other . Factorial analysis confirmed that the falls in pressure attributable to the low-sodium diet and high-potassium diet were not additive . ( ABSTRACT TRUNCATED AT 250 WORDS Phase I of the Trials of Hypertension Prevention was design ed to test the effectiveness and safety of three life-style ( weight loss , sodium restriction , and stress management ) and four nutrition supplement ( calcium , magnesium , potassium , and fish oil ) interventions in reducing diastolic blood pressure ( DBP ) in persons with a high-normal blood pressure . A total of 2182 persons with a DBP between 80 and 89 mm Hg met the eligibility criteria for participation in phase I and were r and omized to one of the active intervention or control treatment groups . Most were white ( 82 % ) , male ( 70 % ) , married ( 76 % ) , nonsmoking ( 88 % ) , college graduate ( 53 % ) , full-time employees ( 91 % ) . The average blood pressure prior to entry into the trial was 124.9 mm Hg systolic and 83.8 mm Hg diastolic . A variety of baseline observations , including sociodemographic characteristics , personal and family medical history , health habits , diet , and biologic measurements , were documented before r and omization and compared among the seven active intervention and control groups . As might be expected in a r and omized trial of this sample size , the distribution of measured baseline characteristics was virtually identical in the treated and control groups . Based on this finding and the knowledge that r and omization procedures were implemented without deviation from the phase I protocol , it is probable that unknown potential confounders were also equally distributed at entry into the study . Given the achievement of high rates of follow-up , subsequent differences in blood pressure are unlikely to have been due to baseline differences between the active treatment and control groups , and can probably be attributed to effects of the active interventions The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease We examined the interactions between sodium and calcium responsiveness of blood pressure by study ing the effects of calcium supplementation in 46 normotensive and hypertensive subjects who had been previously characterized as salt sensitive or salt resistant on the basis of their blood pressure responses to rapid sodium and extracellular volume expansion and contraction . The calcium supplementation study utilized a placebo-controlled , double-blind , r and omized crossover design . Subjects received calcium carbonate supplementation ( 1.5 g/day ) for 8 weeks or matching placebo , with 2-week placebo lead-in and crossover periods . For the entire group , no significant blood pressure changes were seen with calcium supplementation . When the subjects were separated on the basis of race or prior salt sensitivity , significant differences were seen . Blacks and salt sensitive subjects exhibited a significant ( P < .05 ) blood pressure decrease when compared to their counterparts . Calcium sensitive subjects had significantly ( P < .02 ) lower levels of plasma renin activity than those not demonstrating a decrease in blood pressure with added calcium . When urinary calcium excretion of subjects previously defined as salt sensitive or salt resistant were compared , the former had significantly ( P < .001 ) higher calcium excretion values at baseline as well as during the placebo and calcium supplementation periods than did the latter . There were no known differences in dietary calcium intake to account for the striking urinary findings . These observations confirm the heterogeneity of blood pressure response to calcium supplementation and demonstrate congruity between sodium and calcium responsiveness of blood pressure in normal and hypertensive humans . ( ABSTRACT TRUNCATED AT 250 WORDS In a double-blind trial 90 mildly hypertensive subjects aged 16 - 29 years were r and omly assigned to 1 g calcium per day or placebo . Calcium supplementation did not affect systolic blood pressure , but at six and twelve weeks diastolic blood pressure had fallen by 3.1 ( p = 0.04 ) and 2.4 ( p = 0.11 ) mm Hg , respectively , more in the calcium group than it had in the placebo group . Subjects with a baseline plasma parathyroid hormone ( PTH ) higher than the median showed a 6.1 mm Hg ( p = 0.01 ) greater fall in diastolic blood pressure after six weeks and 5.4 mm Hg ( p = 0.01 ) after twelve than in the placebo group . The fall in diastolic blood pressure was greater in the calcium group than in the placebo group in subjects with a lower than median serum total calcium and in those with a large bodyweight . Calcium supplementation may lower blood pressure in young people with mildly raised blood pressure , particularly in those with high plasma PTH and /or low serum total calcium 23 unselected patients with mild to moderate essential hypertension , whose average supine blood pressure after two months ' observation on no treatment was 154/99 mm Hg , were entered into an eight week double blind r and omised crossover study of one month 's treatment with slow release potassium tablets ( 60 mmol/day ) versus placebo without alteration of dietary sodium or potassium intake . By the fourth week mean supine blood pressure had fallen by 4 % on potassium supplementation compared with placebo . Urinary potassium excretion increased from 62 + /- 4.7 mmol/24 h on placebo to 118 + /- 7.4 mmol/24 h on potassium . The fall in blood pressure was not related to urinary sodium excretion before entry to the trial or while on placebo . Moderate potassium supplementation caused a small but significant fall in blood pressure in patients with mild to moderate essential hypertension and could be additive to the effects of moderate sodium restriction . This increase in potassium intake could be achieved with a potassium-based salt substitute and a moderate increase in vegetable and fruit consumption . Moderate dietary sodium restriction with dietary potassium supplementation may obviate or reduce the need for drug treatment in some patients with mild to moderate hypertension It has long been suspected that sodium and potassium intake influence blood pressure . Since both these electrolytes can be modified by diet , attention has focused on decreasing sodium intake and increasing potassium intake as a potential way of treating and preventing hypertension . Several short-term controlled clinical trials have examined the effect of supplemental potassium intake on blood pressure , but with inconsistent results [ 1–8 ] . The Minnesota Mount Sinai Hypertension Trial ( MSHT ) is a double-blind study comparing placebo with potassium supplementation for controlling blood pressure in hypertensive men on a sodium-restricted diet over a 2–3 year follow-up period . At the time of r and omization to placebo or supplemental potassium and through 12 weeks of follow-up , the patients were taking antihypertensive medication . This preliminary report compares blood pressure changes between the placebo and supplemental potassium groups over the first 12 weeks of the trial Objective To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol . Methods The participants were 350 normotensive men and women aged 30–54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention . They were r and omly assigned to receive placebo or 6 g purified fish oil once a day , which supplied 3 g n-3 polyunsaturated fatty acids for 6 months . Results Baseline blood pressure was ( mean ± SD ) 123±9/81 ±5mmHg . The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant . There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile ( 132/87 versus 114/75 mmHg ) , low habitual fish consumption ( 0.4 versus 2.9 times a week ) or low baseline plasma levels of n-3 fatty acids . Fish oil increased HDL2-cholesterol significantly compared with the placebo group . Subgroup analysis showed this effect to be significant in the women but not in the men . Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure . Conclusion Moderate amounts of fish oil ( 6g/day ) are unlikely to lower blood pressure in normotensive persons , but may increase HDL2-cholesterol , particularly in women Twenty patients with mild or moderate essential hypertension and not receiving any drug treatment , who had been moderately restricting their sodium intake to around 70 mmol(mEq ) a day for at least one month and whose mean blood pressure was then 163/103 mm Hg , were entered into a double blind , r and omised crossover study to compare one month 's treatment with slow release potassium chloride tablets ( 64 mmol potassium chloride a day ) with one month 's treatment with a matching placebo . Mean ( SEM ) urinary sodium excretion on entry to the study was 68 ( 6.8 ) mmol/24 h. Mean urinary potassium excretion increased from 67 ( 6.9 ) mmol(mEq)/24 h with placebo to 117 ( 4.6 ) mmol/24 h with potassium chloride . Supine and st and ing systolic and diastolic blood pressures did not change significantly with potassium chloride supplementation when compared with pressures while receiving placebo or before r and omisation . In patients who are able moderately to restrict their sodium intake doubling potassium as a chloride salt has little or no effect on blood pressure In a double-blind , r and omized , placebo-controlled , crossover trial , 23 middle-aged patients with mild to moderate essential hypertension were given an oral calcium supplement ( 1 g/day ) for 8 weeks . At the end of this period , eight patients continued with this treatment for an additional 2 weeks but were also given 0.5 micrograms/day of 1,25-(OH)2 vitamin D3 . In the 21 patients who completed the study , arterial pressure during the calcium-supplemented phase was almost identical to that of the placebo phase . In eight patients , mean arterial pressure ( MAP ) had changed by greater than 5 mmHg at the end of the calcium-supplemented period , compared with the end of the placebo phase ( six patients showed an increase in MAP and two a decrease ) . Changes in arterial pressure were unrelated to age , plasma ionized calcium , parathyroid hormone ( PTH ) , plasma renin activity ( PRA ) , plasma aldosterone , 24-h urinary calcium , sodium and potassium and were only weakly related to body weight . In the eight patients who continued with the treatment of calcium plus 1,25-(OH)2 vitamin D3 after the 8-week study period , arterial pressure changed very little and not significantly . These results do not support the suggestion that calcium supplements lower arterial pressure in middle-aged subjects with mild to moderate essential hypertension Abstract Objective : To examine the effect of a reduced sodium and increased potassium and magnesium intake on blood pressure . Design : R and omised double blind placebo controlled trial . Setting : General population of a suburb of Rotterdam . Subjects : 100 men and women between 55 and 75 years of age with untreated mild to moderate hypertension . Interventions : During 24 weeks the intervention group received a mineral salt ( sodium : potassium : magnesium 8:6:1 ) and foods prepared with the mineral salt . Controls received common salt and foods . Main outcome measure : Change in blood pressure . Results - Complete follow up was achieved for 97 of the 100 r and omised subjects . Systolic blood pressure ( mean of measurements at weeks 8 , 16 , and 24 ) fell by 7.6 mm Hg ( 95 % confidence interval 4.0 to 11.2 ) and diastolic blood pressure by 3.3 mm Hg ( 0.8 to 5.8 ) in the mineral salt group compared with the controls , with a 28 % decrease in urinary sodium excretion and a 22 % increase in urinary potassium excretion . Twenty five weeks after the study the difference in blood pressure between the groups was no longer detectable . Conclusion : Replacing common sodium salt by a low sodium , high potassium , high magnesium mineral salt could offer a valuable non -pharmacological approach to lowering blood pressure in older people with mild to moderate hypertension OBJECTIVE --To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension . DESIGN --A double blind , r and omised , placebo controlled , crossover trial of 32 weeks ' duration . SETTING S -- Cardiology outpatient department , Sassoon General Hospitals , Pune , India . PATIENTS --37 Adults with mild hypertension ( diastolic blood pressure less than 110 mm Hg ) . INTERVENTION-- Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design . No other drug treatment was allowed . MEASUREMENTS --Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals . RESULTS --Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures ( p less than 0.001 ) and a significant reduction in serum cholesterol concentration ( p less than 0.05 ) ; other biochemical variables did not change . Magnesium did not have an additional effect . Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium . The drug was well tolerated and compliance was satisfactory . CONCLUSION --Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension . Giving magnesium as well has no added advantage Eighteen unselected patients with untreated mild to moderate essential hypertension , whose average supine blood pressure after 2 months ' observation on no treatment was 154/103 mmHg , were entered into a double-blind r and omized crossover study of 1 month 's treatment with calcium lactate gluconate ( 40 mmol of elemental calcium/day ) and treatment with placebo for a further month . Despite a significant increase in total plasma calcium ( P less than 0.01 ) and in 24-h urinary excretion of calcium ( P less than 0.025 ) while taking calcium lactate gluconate , there was no fall in blood pressure with calcium supplementation compared to treatment with placebo This longitudinal trial investigated the effects of calcium supplementation on the mean 24-hour blood pressure in African-American adolescents . Subjects were self-identified African-American adolescents from a high school in a suburb of Los Angeles , California . The subjects were r and omly placed in a placebo or treatment group ( placebo versus 1.5 g of calcium/day x 4 weeks ) . Follow-up mean 24-hour ambulatory blood pressure ( ABP ) for both the treatment and control groups was lower than the baseline mean 24-hour ABP . In the treatment group , there was a decrease of 2.2 mm Hg in the mean systolic blood pressure and 0.7 mm Hg in the diastolic blood pressure . Relative to the placebo group , the net change in ABP was -1.7 mm Hg for systolic blood pressure and -0.5 mm Hg for the diastolic blood pressure . There was no statistically significant effect of calcium supplementation on the 24-hour mean ABP . The net effect of supplementation on ABP during waking and sleeping hours also was not significant The blood pressure response of 48 hypertensive persons and 32 normotensive persons to elemental calcium ( as the carbonate or citrate salt ) , 1000 mg/d for 8 weeks , was assessed in a r and omized , double-blind , placebo-controlled , crossover trial . Compared with placebo , Ca2 + significantly lowered supine systolic blood pressure by 3.8 mm Hg , st and ing systolic blood pressure by 5.6 mm Hg ( p less than 0.02 ) , and supine diastolic blood pressure by 2.3 mm Hg ( p less than 0.05 ) in hypertensive persons . The response in normotensive persons differed significantly from that in hypertensives ( p less than 0.03 ) as their blood pressure was unchanged . Twenty-one ( 44 % ) hypertensive and 6 ( 19 % ) normotensive persons achieved a reduction in st and ing systolic arterial pressure of 10 mm Hg or greater . Reported adverse effects were similar between calcium and placebo phases and did not necessitate withdrawal of any patient from the trial . Treatment with 1000 mg/d of oral Ca2 + for 8 weeks represents a safe , well-tolerated , nonpharmacologic intervention that lowers blood pressure in selected patients with mild to moderate hypertension Ninety-one middle-aged men and women with untreated mild hypertension were allocated to a nopharmacological treatment group or to a control group . Members of the treatment group were instructed to reduce daily sodium intake to less than 70 mmol , to reduce the intake of saturated fat , to lose weight if necessary and to perform regular physical exercise and relaxation training . Adherence to and effects of the programme on blood pressure and serum lipids were monitored for 12 months . In the treatment group , daily sodium excretion decreased to and remained at 50 % of its original level ( P less than 0.001 ) , and there was a significant reduction in saturated fat intake . The average weight reduction was modest . Adherence to physical exercise and relaxation training regimens was poor . The net decreases ( difference in changes between treatment and control group ) in blood pressure were greatest during the first 3 months : in men the decrease in systolic blood pressure was 11.3 mmHg ( P less than 0.001 ) and in diastolic blood pressure 8.3 mmHg ( P less than 0.001 ) ; in women the decrease in systolic blood pressure was 10.8 mmHg ( P less than 0.01 ) and in diastolic blood pressure 6.4 mmHg ( P less than 0.01 ) . However , this decrease diminished during the last 3 months to approximately one half owing to blood pressure reduction in controls . Low density lipoprotein cholesterol levels decreased significantly in treated men and women Changes in potassium balance have been found to have variable effects on the blood pressure of animals , and the administration of potassium supplements has been reported to lower the blood pressure of normokalemic hypertensive patients . To assess the effect of potassium repletion in hypokalemic hypertension , we administered either potassium chloride , 60 mmol per day , or placebo tablets , each for six weeks , in a r and omized , double-blind , crossover trial to 16 hypertensive patients who had diuretic-induced hypokalemia and who continued to take a constant amount of diuretic . We selected patients whose control serum potassium levels were below 3.5 mmol per liter . In association with an average rise in the serum potassium concentration of 0.56 mmol per liter , the mean blood pressure fell by an average of 5.5 mm Hg ( P = 0.004 ) , with at least a 4 mm Hg fall observed in 9 of the 16 patients . The fall in blood pressure correlated with a fall in plasma renin activity ( r = 0.568 , P = 0.043 ) but not with changes in plasma aldosterone levels or other variables . We conclude that short-term potassium supplementation that ameliorates diuretic-induced hypokalemia may induce a significant fall in blood pressure In order to eludicate possible mechanism(s ) involved in the blood pressure reduction induced by potassium ( K ) supplementation , we studied the changes of BP and of some of its regulatory systems , including levels of urinary kallikrein (UKal)--an index of renal kallikrein production . Twenty-four untreated essential hypertensives , with a basal BP of 147/96 + /- 13/7 mmHg and normal renal function , received in crossover , double-blind , r and omised fashion , 64 mmol KCl or placebo during two periods of 4 weeks each . At the 4th week of potassium supplementation systolic , diastolic and mean BPs decreased by 6.3 + /- 2 ( P less than 0.01 ) , 3.0 + /- 2 and 4.1 + /- 2 ( P less than 0.05 ) mmHg respectively for the supine position , and 5.0 + /- 2 , 4.0 + /- 2 ( P less than 0.05 ) and 4.0 + /- 1 ( P less than 0.05 ) mmHg for the st and ing position . Urinary potassium ( K ) increased from 55 + /- 4 to 123 + /- 6 mmol/24 hours ( P less than 0.001 ) and UKal from 692 + /- 69 to 1052 + /- 141 mU/24 hours ( P less than 0.01 ) . Serum K rose from 3.8 + /- 0.1 mEq/l to 4.1 + /- 0.1 mmol/l ( P less than 0.001 ) and PRA from 0.77 + /- 0.12 to 0.99 + /- 0.14 ng/ml/h ( P less than 0.05 ) . Correlations were observed between UKal and urinary K ( r = 0.44 , P less than 0.0001 ) ; between differences in UKal and urinary K and in UKal and urinary Na ( r = 0.50 , P less than 0.0005 and r = 0.48 , P less than 0.001 respectively ) . ( ABSTRACT TRUNCATED AT 250 WORDS 1 . In order to confirm and investigate the hypotensive effect of a high potassium intake we compared mean arterial pressure ( MAP ) , water and electrolyte balance , plasma and urinary noradrenaline ( NA ) , plasma renin activity ( PRA ) and plasma aldosterone concentration ( PAC ) in 20 in patients with mild or moderate essential hypertension on a control diet ( Na : 260 , K : 75 mmol/day ) , and after high ( K : 175 mmol/day ) and low potassium diets ( K : 25 mmol/day ) . 2 . After potassium loading , urinary volume ( UV ) and urinary excretion of sodium ( U Na V ) and of potassium ( U K V ) were elevated , and MAP , body weight , plasma volume ( PV ) , extracellular fluid volume ( ECFV ) and total exchangeable sodium ( Na e ) were reduced significantly . 3 . After potassium loading , PRA , PAC , plasma and urinary NA increased and the pressor response to infused noradrenaline and angiotensin II decreased significantly . 4 . The reduction of MAP after potassium loading correlated positively with PV and ECFV during the control period . In addition , significant correlations were found between ΔUV and Δ U Na V , —ΔPV and Δ U / Na V , —ΔPV and Δ plasma NA , and Δ plasma NA and Δ PRA . 5 . Patients with low PRA had high PV , ECFV and Na e during the control period , and showed greater reductions of MAP , PV , ECFV and Na e after potassium loading . 6 . After potassium restriction , U Na V , PRA and urinary NA decreased and PV increased , and MAP did not change significantly . 7 . These results suggest that the hypotensive effect of high potassium intake may be caused by reduction of body fluid volume via augmentation of Na excretion We used 24-h monitoring of blood pressure ( BP ) to evaluate the effect of calcium supplementation on mild to moderate essential hypertension in elderly hospitalized patients for the first time in a controlled crossover study . The mean systolic and diastolic BP over a period of 24 h declined by 13.6 mm Hg ( P less than .005 ) and 5.0 mm Hg ( P less than .05 ) respectively in patients whose diet was supplemented with 1 g of elemental calcium in the form of oystershell electrolysate ( AA calcium ) . Serum ionized calcium and urinary calcium and sodium excretion increased ( serum Ca2 + 0.16 + /- 0.03 mEq/L , P less than .05 ; FECa 0.5 + /- 0.2 % , P less than .05 ; FENa 0.4 + /- 0.1 % , P less than .05 ) and plasma parathyroid hormone was suppressed ( 12.2 + /- 2.3 pg/mL , P less than .005 ) . These data suggest that supplementation of dietary calcium may contribute to a reduction of BP in elderly patients with essential hypertension A r and omised double-blind cross-over study of increased oral potassium 64 mmol a day versus placebo was conducted in 20 young healthy males on normal sodium unrestricted diet . A significantly greater proportion had lower systolic and diastolic blood-pressures on potassium than on placebo . The mean diastolic pressure was significantly lowered , by 2.4 mm Hg , during potassium supplementation . Change in diastolic pressure correlated negatively with change in 24-hour urinary potassium and positively which change in 24-hour urinary sodium/potassium ratio in individual subjects Clinical and epidemiologic studies suggest that the intake of potassium chloride lowers blood pressure . To investigate whether supplemental potassium chloride ( 96 mmol of microcrystalline potassium chloride a day ) reduced the need for antihypertensive medication in hypertensive men on a restricted-sodium diet , we conducted a r and omized , placebo-controlled , double-blind clinical trial . A total of 287 men 45 to 68 years of age , 142 given potassium chloride and 145 given placebo , were followed for an average of 2.2 years after the withdrawal of their antihypertensive medication . Men in both groups received instructions on following a low-sodium diet . Overnight urinary sodium excretion fell from 63 mmol per eight hours at base line to an average of 45 mmol per eight hours during follow-up . Participants given supplemental potassium chloride had significantly higher ( P less than 0.001 ) serum potassium levels and urinary potassium excretion ( averaging 4.5 mmol per liter and 42.5 mmol per eight hours , respectively ) during follow-up than participants given placebo ( 4.2 mmol per liter and 20.0 mmol per eight hours ) . Seventy-nine participants in each group required reinstitution of antihypertensive medication according to strict indications defined by the protocol . No significant differences in systolic or diastolic blood pressure were observed between the two groups . During follow-up , systolic and diastolic blood pressure averaged 130.6 and 82.5 mm Hg , respectively , for participants given supplemental potassium , and 132.5 and 83.1 mm Hg for participants given placebo . We conclude that supplemental potassium chloride does not reduce the need for antihypertensive medication in hypertensive men on a restricted-sodium diet Sodium ( Na ) restriction and potassium ( K ) supplementation has been recommended as treatment of essential hypertension but the mechanism by which these may reduce blood pressure ( BP ) is unknown . We examined if moderately reduced Na intake , combined with a low-Na/high-K salt alternative ( Pansalt : NaCl 57 % , KCl 28 % , MgSO4 12 % ) as substitute for st and ard table salt , induced clinical ly significant BP reduction in hypertensive patients and , if this therapy reduced total peripheral resistance . After a 2-month control period 40 patients aged 21 - 67 years with mean casual BP 156/103 mmHg were given a salt restricted diet ( 120 mmol Na/24 h ) for 6 months . In addition , they were r and omised in a double-blind manner to receive either Pansalt ( P-group ) or st and ard NaCl ( S-group ) as table salt in small amounts . Cardiac output was measured by dye dilution . Daily Na excretion was similarly reduced ( 20 % ) in both groups while K excretion was slightly increased in the P-group and reduced in the S-group ( difference p < 0.05 ) . No large changes occurred in 24-h ambulatory BP ( by Accutracker II ) or intraarterial pressure ( through a brachial artery catheter ) at rest or during exercise while casual BP was reduced ( p < 0.05 ) 13/8 mmHg in the P-group and 8/5 mmHg in the S-group . While cardiac output was slightly reduced at rest and during 50W exercise in the P-group , no significant changes were seen in total peripheral resistance in either group . Thus , moderate reduction in Na intake , with or without addition of K , is not sufficient to induce significant long-term intraarterial or 24-h ambulatory BP changes in essential hypertension . Without BP changes invasively determined central hemodynamics remains remarkably stable over a 6-month period This was a r and omized and double-blind study to examine : ( 1 ) the effect of a 1500 mg/day calcium supplement vs a placebo for 8 wk in 42 adults with high normal or mildly elevated blood pressure ( BP ) and , ( 2 ) the relationship between baseline serum total calcium levels and BP response to calcium supplementation . Following the experimental protocol , mean pressures were lower in the treatment vs placebo group ( 95.7 mmHg and 102.1 mmHg , p = 0.002 ) , but response was not related to initial serum total calcium levels . After 8 wk of calcium supplementation , serum total calcium was greater in the treatment group compared to the placebo group ( p = 0.02 ) . Within the treatment group only , the change in total serum calcium was related to the change in parathyroid hormone ( r = -0.92 , p = 0.0002 ) ; and the change in ionized calcium was related to the change in parathyroid hormone ( r = -0.68 , p = 0.03 ) in the subgroup with low baseline serum total calcium . This study provides further support for the hypotensive effect of supplemental calcium in some people . However , it fails to clarify or exp and upon previous reports that a low serum total calcium level might be predictive of the blood pressure response to increased calcium It has been cl aim ed that calcium lowers BP . The present r and omised , double-blind , placebo-controlled crossover study is the first to investigate the effect on BP of a high oral dose of calcium given for a long period to patients with previously untreated hypertension . Elemental calcium ( 2 g ) was administered for 12 weeks interchanging with a period of 12 weeks of placebo . Twenty patients completed the protocol . There was no significant difference in change of BP during the period of additional calcium intake when compared with placebo ( P = 0.33 ) . The risk of not detecting a real BP-lowering effect of calcium of at least 3 mmHg was < 5 % . No evidence for the existence of a subgroup of ' responders ' was found . It is concluded that a high daily dose of calcium supplementation given for 12 weeks does not decrease BP in previously untreated patients with mild to moderate hypertension A multicentre study , involving 358 subjects , was carried out to evaluate the effects of a low-Na/high-K dietary salt in hypertensive patients receiving beta-blocker monotherapy . At the end of a 4-week treatment period with 200 mg slow-release metoprolol patients were r and omly divided into two groups : one group was given common salt and the other the dietary salt . Both salts were given at table , in double-blind conditions over a period of 4 weeks . The dietary salt group showed a systolic and diastolic blood pressure ( BP ) reduction ( 4.2 and 3.0 mmHg , respectively , in the supine position and 4.0 and 2.5 mmHg in the st and ing position ) , which was virtually absent in the common salt group . A statistically significant difference between the two groups was found only between the systolic values ( P less than 0.05 ) . Twenty-four-hour urinary sodium excretion did not change in either group , while the excretion of 24-h urinary potassium increased significantly in the dietary salt group . It is concluded that in mild or moderately hypertensive patients already receiving a beta-blocker , ancillary treatment with a low-Na/high-K salt can be expected to lead to a further , slight reduction in systolic BP , probably due to the daily potassium load ( around 20 mmol ) Phase II of the Trials of Hypertension Prevention ( TOHP II ) is a multicenter , controlled clinical trial design ed to test whether weight loss , a reduced sodium intake , or a combination of weight loss and a reduced sodium intake will lower blood pressure ( BP ) and prevent the occurrence of hypertension . The study population consists of middle-aged , moderately overweight individuals with a diastolic BP between 83 and 89 mm Hg . Of the 2382 r and omized participants , 816 ( 34 % ) are female and 494 ( 21 % ) are from a racial or ethnic minority background . At baseline , mean dietary intakes of sodium , based on measurements of 24-hour urinary excretion , were 199 mmol/d in men and 154 mmol/d in women . The average body mass index was 30.9 kg/m2 . Across the four r and omized groups , there was no substantial imbalance in the distribution of baseline variables ; however , the mean age in the four groups was slightly but significantly different ( range : 43.2 to 44.2 years , P = 0.02 ) . A comparison of baseline characteristics of TOHP II participants with those of participants in three other primary prevention trials reveals a high level of mean dietary sodium intake in each study . Data reported in this article indicate that any subsequent differences in BP among the r and omized groups are unlikely to result from maldistribution of known confounding variables at baseline . Finally , because of the high prevalence of overweight and excessive sodium intake in the United States , results from TOHP II should be broadly applicable to the general population OBJECTIVE To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure . DESIGN R and omized control multicenter trials . SETTING Volunteers recruited from the community , treated and followed up at special clinics . PARTICIPANTS Of 16,821 screenees , 2182 men and women , aged 30 through 54 years , with diastolic blood pressure from 80 through 89 mm Hg were selected . Of these , 50 did not return for follow-up blood pressure measurements . INTERVENTIONS Three life-style change groups ( weight reduction , sodium reduction , and stress management ) were each compared with unmasked nonintervention controls over 18 months . Four nutritional supplement groups ( calcium , magnesium , potassium , and fish oil ) were each compared singly , in double-blind fashion , with placebo controls over 6 months . MAIN OUTCOME MEASURES Primary : change in diastolic blood pressure from baseline to final follow-up , measured by blinded observers . Secondary : changes in systolic blood pressure and intervention compliance measures . RESULTS Weight reduction intervention produced weight loss of 3.9 kg ( P less than .01 ) , diastolic blood pressure change of -2.3 mm Hg ( P less than .01 ) , and systolic blood pressure change of -2.9 mm Hg ( P less than .01 ) . Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h ( P less than .01 ) , diastolic blood pressure by 0.9 mm Hg ( P less than .05 ) , and systolic blood pressure by 1.7 mm Hg ( P less than .01 ) . Despite good compliance , neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly ( P greater than .05 ) . CONCLUSIONS Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons . Sodium reduction is also effective . The long-term effects of weight reduction and sodium reduction , alone and in combination , require further evaluation The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive , moderately obese participants using a 3 x 3 factorial design . Drugs evaluated were placebo , diuretic ( chlorthalidone ) , and beta-blocker ( atenolol ) ; diets were usual ( no intervention ) , weight reduction , and low sodium/high potassium ( Na/K ) . This article reports 6-month dietary changes and the effect of dietary change on blood pressure . Six-month mean weight change was -4.7 kg in the weight reduction group , -0.3 kg in the Na/K group , and -0.5 kg in the usual-diet group . At 6 months , daily electrolyte excretion had changed in the Na/K intervention group . Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group . Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group , from 57.0 to 60.5 mmol in the weight reduction group , and from 55.3 to 59.1 mmol in the usual diet group . Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol . Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification Epidemiological and prospect i ve studies in man and animals have indicated an inverse relationship between calcium intake and cardiovascular mortality and blood pressure ( BP ) . We have therefore studied the effect of dietary calcium on blood pressure in two groups of women . In a cross-sectional study 103 early postmenopausal women were stratified into three groups according to daily calcium intake calculated from a question naire . Both diastolic and systolic blood pressures were identical in the three groups . We thereafter conducted a prospect i ve placebo-controlled trial on the effect of calcium supplementation . Twenty-eight healthy women were r and omized to placebo treatment ( n = 14 ) or calcium supplementation 2,000 mg daily ( n = 14 ) for one year . In both groups BP remained at initial levels throughout the study and was identical in the two groups at measurements every three months . We thus conclude that calcium supplementation has no effect on BP in normotensive subjects on a high calcium diet Epidemiologic and animal studies have suggested an inverse relationship between calcium intake and BP . Furthermore , calcium intake seems to be inversely correlated with the incidence of eclampsia in pregnancy . In a r and omized clinical trial , young adults were allocated to a calcium-supplemented group receiving 1 g/day of elemental calcium ( 15 men and 15 women ) or a placebo group ( 14 women and 13 men ) for a period of 22 weeks . The calcium-supplemented group showed a significant decrease in diastolic BP ; this effect was stabilized after nine weeks in women and six weeks in men . The reduction in diastolic BP was 5.6 % and 9 % from the initial values for women and men , respectively . This study supports epidemiologic and animal evidence of the effect of calcium intake on BP and suggests the need for more research exploring the mechanisms involved in the observed effect |
2,102 | 26,543,179 | IMPLICATION S The Confusion Assessment Method was the most widely used instrument to identify delirium , however , specific training is required to ensure optimum performance .
The Delirium Rating Scale and its revised version performed best in the psychogeriatric population but requires an operator with psychiatric training .
The Nurses ' Delirium Screening Checklist appears best suited to the surgical and recovery room setting .
The Single Question in Delirium shows promise in oncology patients .
The Memorial Delirium Assessment Scale , while demonstrating good measures of validity in the surgical and palliative care setting , may be better used a measure of delirium severity . | BACKGROUND Delirium occurs commonly in hospitalized older patients but is poorly recognized .
Although there are a plethora of vali date d delirium screening tools , it is unclear which tool best suits particular population s. PURPOSE To evaluate validation studies of delirium screening tools in non-critically ill hospital in patients and provide guidance on the choice of screening tool . | BACKGROUND Delirium occurs commonly among older hospitalized patients and is frequently not recognized . In an effort to identify tools useful to clinicians in the diagnosis of delirium , test characteristics of four screening instruments were compared . METHODS Patients 65 years of age or older who were admitted to one of four medical and surgical wards of a university teaching hospital were followed up prospect ively . Potential subjects were excluded if unavailable for interviews or discharged within 48 hours of admission , or if judged too impaired to participate in the daily interviews . Research assistants administered four instruments used to detect delirium : Digit Span Test , Vigilance ' A ' Test , Clinical Assessment of Confusion , and Confusion Assessment Method . Abnormal scores on these tests or suspicion of acute confusion prompted a referral to the clinician-investigators who then assessed the patient daily for delirium based on the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition criteria . RESULTS Delirium occurred in 64 ( 14.8 % ) of 432 subjects . The positive likelihood ratios for all of the instruments were significantly more than 1 . The instruments remained useful when applied to selected subgroups : subjects in whom acute mental status changes were documented , subjects on surgical services , and subjects with impaired cognitive status on admission . Combinations of any two instruments did not perform substantially better than the instrument with the best test characteristics : the Clinical Assessment of Confusion . All instruments were more useful at confirming delirium than in excluding it . CONCLUSION The four instruments studied , which are suitable for use at the bedside , can aid the clinician in identifying patients likely to be suffering from delirium OBJECTIVES This paper aim ed to measure the prevalence and outcomes of delirium for patients over 70 admitted to a general hospital for acute medical care and to assess the validity of the Delirium Rating Scale-Revised-98 ( DRS-R-98 ) in this setting . METHODS Prospect i ve study in a British acute general hospital providing sole emergency medical services for its locality . We screened consecutive patients over 70 with an unplanned emergency hospital admission and recruited a cohort of 249 patients likely to have mental health problems . They were assessed for health status at baseline and followed over 6 months . A sub- sample of 93 participants was assessed clinical ly for delirium . RESULTS 27 % ( 95 % confidence interval ( CI ) 23 - 31 ) of all older medical patients admitted to hospital had DRS-diagnosed delirium , and 41 % ( 95 % CI 37 - 45 ) had dementia ( including 19 % with co-morbid delirium and dementia ) . Compared with clinician diagnosis , DRS-R-98 sensitivity was at least 0.75 , specificity 0.71 . Compared with reversible cognitive impairment , sensitivity was at least 0.50 , specificity 0.67 . DRS-diagnosed delirium was associated with cognitive impairment , mood , behavioural and psychological symptoms , activities of daily living , and number of drugs prescribed , supporting construct validity . Of those with DRS-diagnosed delirium , 37 % died within 6 months ( relative risk 1.4 , 95 % CI 0.97 - 2.2 ) , 43 % had reversible cognitive impairment , but only 25 % had clinical ly important recovery in activities of daily living . Behavioural and psychological symptoms were common and mostly resolved , but new symptoms frequently developed . CONCLUSION Delirium is common . Some , but not all , features are reversible . DRS-R-98 has reasonable validity in population s where co-morbid dementia is prevalent OBJECTIVE To develop and vali date a new st and ardized confusion assessment method ( CAM ) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk setting s. DESIGN Prospect i ve validation study . SETTING Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University ( site 1 ) and in general medicine wards at the University of Chicago ( site 2 ) . PATIENTS The study included 56 subjects , ranging in age from 65 to 98 years . At site 1 , 10 patients with and 20 without delirium participated ; at site 2 , 16 patients with and 10 without delirium participated . MEASUREMENTS AND MAIN RESULTS An expert panel developed the CAM through a consensus building process . The CAM instrument , which can be completed in less than 5 minutes , consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders ( DSM-III-R ) . An a priori hypothesis was established for the diagnostic value of four criteria : acute onset and fluctuating course , inattention , disorganized thinking , and altered level of consciousness . The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion . At both sites , the diagnoses made by the CAM were concurrently vali date d against the diagnoses made by psychiatrists . At sites 1 and 2 values for sensitivity were 100 % and 94 % , respectively ; values for specificity were 95 % and 90 % ; values for positive predictive accuracy were 91 % and 94 % ; and values for negative predictive accuracy were 100 % and 90 % . The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium . The CAM was shown to have convergent agreement with four other mental status tests , including the Mini-Mental State Examination . The interobserver reliability of the CAM was high ( kappa = 0.81 - 1.0 ) . CONCLUSIONS The CAM is sensitive , specific , reliable , and easy to use for identification of delirium Background : Major depression is a frequent and serious disorder in older medical in patients . Because the condition goes undetected and untreated in most of these patients , we conducted a r and omized clinical trial to evaluate the effectiveness of a strategy of systematic detection and multidisciplinary treatment of depression in this population . Methods : Consecutive patients aged 65 years or more admitted to general medical services in a primary care hospital between October 1999 and November 2002 were screened for depression with the Diagnostic Interview Schedule ( DIS ) within 48 hours after admission . Patients found to have major depression were r and omly allocated to receive the intervention or usual care . The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient 's family physician . Research assistants , blind to group allocation , collected data from the patients at enrolment and at 3 and 6 months later using the Hamilton Depression Rating Scale ( HAMD ) , the Medical Outcomes 36-item Short Form ( SF-36 ) , the DIS , the Mini-Mental State Examination ( MMSE ) , the Older Americans Re sources and Services ( OARS ) question naire to assess basic and instrumental activities of daily living ( OARS-ADL and OARS-IADL ) and the Rating Scale for Side Effects . Data on the severity of illness , length of hospital stay , health services and medication use , mortality and process of care were also collected . The primary outcome measures were the HAMD and SF-36 . Results : Of 1500 eligible patients who were screened , 157 were found to have major depression and consented to participate ( 78 in the intervention group and 79 in the usual care group ) . At r and omization , there were no clinical ly or statistically significant differences between the 2 groups . Sixty-four patients completed follow-up to 6 months , 57 withdrew , and 36 died . At 6 months , there were no clinical ly or statistically significant differences the 2 groups in HAMD or SF-36 scores or any of the secondary outcome measures . Interpretation : We were unable to demonstrate that systematic detection and multidisciplinary care of depression was more beneficial than usual care for elderly medical in patients Delirium is a common neuropsychiatric complication in patients with advanced cancer . The Memorial Delirium Assessment Scale ( MDAS ) is a recently developed 10‐item severity rating instrument . The purpose of the current prospect i ve study was to further assess the clinical utility , factor structure , and validity of the MDAS in a relatively homogeneous population of patients with advanced cancer The purpose of this study undertaken in an acute care hospital was to evaluate sensitivity and specificity of the documentation of nurse-reported delirium symptoms in medical charts . This is a descriptive study based on the clinical assessment s of a study nurse and nursing notes in the medical charts of 226 delirious older patients newly admitted to an acute care hospital . The results of this prospect i ve validation study indicated that documentation of delirium symptoms is poor . Disorientation , agitation and altered level of consciousness were the three symptoms yielding a higher level of sensitivity , but even so said symptoms were reported in less than a third of the medical charts . Univariate analysis suggested that higher comorbidity level , more severe symptoms of delirium and the use of physical restraints were associated with more valid documentation of delirium symptoms in medical charts . Lastly , this study corroborates results of previous studies , indicating that documentation of delirium symptoms in medical charts can be improved . Future study should target improving nurse documentation of delirium symptoms in medical charts very elderly subjects without the APOE4 allele . Am J Geriatr Psychiatry 2008 ; 16 : 781–5 . 21 . Verghese J , Lipton RB , Hall CB , Kuslansky G , Katz MJ . Low blood pressure and the risk of dementia in very old individuals . Neurology 2003 ; 61 : 1667–72 . 22 . Johnson DK , Wilkins CH , Morris JC . Accelerated weight loss may precede diagnosis in Alzheimer disease . Arch Neurol 2006 ; 63 : 1312–7 . 23 . Goldman WP , Morris JC . Evidence that age-associated memory impairment is not a normal variant of aging . Alzheimer Dis Assoc Disord 2001 ; 15 : 72–9 . 24 . Str and berg TE , Tilvis RS . C-reactive protein , cardiovascular risk factors , and mortality in a prospect i ve study in the elderly . Arterioscler Thromb Vasc Biol 2000 ; 20 : 1057– 60 . 25 . Schupf N , Tang MX , Albert SM et al. Decline in cognitive and functional skills increases mortality risk in nondemented elderly . Neurology 2005 ; 65 : 1218–26 . 26 . Williams GC . Pleiotropy , natural selection , and the evolution of senescence . Evolution 1957 ; 11 : 398–411 . 27 . Toupance B , Godelle B , Gouyon PH , Schachter F. A model for antagonistic pleiotropic gene action for mortality and advanced age . Am J Hum Genet 1998 ; 62 : 1525–34 . doi : 10.1093/ageing/afn278 Published electronically 15 January OBJECTIVE To determine how an ultra-brief structured tool that would require usually less than a minute for delirium assessment compares with a clinical assessment based on Diagnostic and Statistical Manual-IV ( DSM-IV ) in a geriatric postacute care ( PAC ) rehabilitation unit . DESIGN Prospect i ve observational cohort study . SETTING Postacute geriatric hospital ward of a Veteran 's Affairs hospital . PARTICIPANTS Consecutively admitted patients between 50 and 100 years old for inpatient postacute medical care . MEASUREMENTS Two teams , blinded to one another 's evaluations , performed daily delirium assessment s using either the Confusion Assessment Method for the intensive care unit ( CAM-ICU ) or clinical assessment based on DSM-IV . RESULTS There were 61 patients enrolled ( median 73 years old , range : 52 - 94 ) , who underwent 521 paired observations . Delirium was detected in 18 patients ( 29.5 % ) by one of the two screening methods over the course of the study , most of whom ( 14 patients , 23 % ) were delirious on the first day of enrollment . Delirium was identified by the CAM-ICU on 12.6 % of the observations and by the clinical assessment on 6 % of the observations ( κ = 0.25 , 95 % confidence interval [ CI ] : 0.09 , 0.40 ) . Examination of disagreement between the 2 evaluations revealed that patients with dementia ( κ = 0.11 , 95 % CI : -0.14 , 0.27 ) had 10.7 times higher odds ( 95 % CI : [ 3.1 , 36.8 ] , p value < .001 ) of having discordance than patients without dementia . CONCLUSIONS Different delirium assessment s may disagree depending on the study population . Dementia patients are especially challenging to evaluate for delirium Pfeiffer 's Short Portable Mental Status Question naire ( SPMSQ ) is a brief screening test for organic brain syndromes . The validity of the SPMSQ was evaluated in a r and om sample of 119 community residents and 282 consecutively admitted medical in patients . The SPMSQ proved to be a sensitive and specific screening test for moderate to severe dementia both in the community and hospital . Using the cut-off point ( number of errors accepted ) of three errors , the sensitivity of the test was 86.2 % and the specificity 99.0 % among medical in patients . The percentages in the community sample were 66.7 % and 100 % , respectively . The validity of the SPMSQ was not as good for delirium because of its variable clinical picture . For screening purpose s lower cut-off points than previously recommended should be used : three errors for dementia and two errors for delirium . Among Finnish elderly people it was not necessary to use correction for education in the SPMSQ BACKGROUND Clinical practice guidelines have been developed to improve screening , prevention and management of delirium . AIMS To implement delirium guidelines in general medical patients to reduce incidence and duration of delirium and improve outcomes in delirious patients . METHODS Implementation was led by a multidisciplinary team of clinicians and project staff on one medical ward . Evaluation was undertaken as a controlled trial in patients aged 65 years or older with/at risk of delirium , compared with a control medical ward . Interventions included risk screening , delirium detection , multidisciplinary education , ward modifications including a four-bed delirium bay , behaviour and medication protocol s , and use of nursing assistant and volunteers . Primary outcome measures were incidence and duration of delirium ; secondary outcomes were length of stay , mortality , falls and discharge destination in delirious subgroup . Process measures included ward moves , use of neuroleptics , allied health review and delirium bay use . RESULTS Of 206 consenting older medical patients , 22 % were delirious at admission and 44 % were at risk . No incident cases of delirium were identified . In the delirious subgroup , significantly fewer intervention participants were discharged with persistent delirium ( 32 % vs 71 % , P = 0.016 ) , with trends to reduced inpatient mortality ( 0 % vs 18.5 % , P = 0.07 ) and falls ( 11 % vs 22 % , P = 0.16 ) , at the expense of a longer medical ward stay ( 16 days vs 8 days , P = 0.01 ) . CONCLUSIONS Low incidence of new delirium may reflect the established interdisciplinary care environment . Improved outcomes in the delirious group are encouraging although implementation was costly , including increased length of acute ward stay OBJECTIVES To investigate whether an education program and a reorganization of nursing and medical care improved the outcome for older delirious patients . DESIGN Prospect i ve intervention study . SETTING Department of General Internal Medicine , Sundsvall Hospital , Sweden . PARTICIPANTS Four hundred patients , aged 70 and older , consecutively admitted to an intervention or a control ward . INTERVENTION The intervention consisted of staff education focusing on the assessment , prevention , and treatment of delirium and on caregiver-patient interaction . Reorganization from a task-allocation care system to a patient-allocation system with individualized care . MEASUREMENTS The patients were assessed using the Organic Brain Syndrome Scale and the Mini-Mental State Examination on Days 1 , 3 , and 7 after admission . Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS Delirium was equally common on the day of admission at the two wards , but fewer patients remained delirious on Day 7 on the intervention ward ( n=19/63 , 30.2 % vs 37/62 , 59.7 % , P=.001 ) . The mean length of hospital stay+/-st and ard deviation was significantly lower on the intervention ward then on the control ward ( 9.4+/-8.2 vs 13.4+/-12.3 days , P<.001 ) especially for the delirious patients ( 10.8+/-8.3 vs 20.5+/-17.2 days , P<.001 ) . Two delirious patients in the intervention ward and nine in the control ward died during hospitalization ( P=.03 ) . CONCLUSION This study shows that a multifactorial intervention program reduces the duration of delirium , length of hospital stay , and mortality in delirious patients OBJECTIVES To identify the prevalence of geriatric syndromes in the premorbid for all syndromes except falls ( preadmission ) , admission , and discharge assessment periods and the incidence of new and significant worsening of existing syndromes at admission and discharge . DESIGN Prospect i ve cohort study . SETTING Three acute care hospitals in Brisbane , Australia . PARTICIPANTS Five hundred seventy-seven general medical patients aged 70 and older admitted to the hospital . MEASUREMENTS Prevalence of syndromes in the premorbid ( or preadmission for falls ) , admission , and discharge periods ; incidence of new syndromes at admission and discharge ; and significant worsening of existing syndromes at admission and discharge . RESULTS The most frequently reported premorbid syndromes were bladder incontinence ( 44 % ) , impairment in any activity of daily living ( ADL ) ( 42 % ) . A high proportion ( 42 % ) experienced at least one fall in the 90 days before admission . Two-thirds of the participants experienced between one and five syndromes ( cognitive impairment , dependence in any ADL item , bladder and bowel incontinence , pressure ulcer ) before , at admission , and at discharge . A majority experienced one or two syndromes during the premorbid ( 49.4 % ) , admission ( 57.0 % ) , or discharge ( 49.0 % ) assessment period . The syndromes with a higher incidence of significant worsening at discharge ( out of the proportion with the syndrome present premorbidly ) were ADL limitation ( 33 % ) , cognitive impairment ( 9 % ) , and bladder incontinence ( 8 % ) . Of the syndromes examined at discharge , a higher proportion of patients experienced the following new syndromes at discharge ( absent premorbidly ) : ADL limitation ( 22 % ) ; and bladder incontinence ( 13 % ) . CONCLUSION Geriatric syndromes were highly prevalent . Many patients did not return to their premorbid function and acquired new syndromes To develop and vali date a screening strategy for delirium within the inter RAI Acute Care comprehensive assessment system . Prospect i ve validation cohort study . Acute general medical wards in two acute care metropolitan hospitals in Brisbane , Australia . Two hundreds thirty-nine subjects with and without delirium , aged 70 and older . Trained research nurses assessed subjects within 36 hours of hospital admission using the inter-RAI acute care ( AC ) system which includes four observational delirium items : Acute change mental status from baseline ( ACMS ) , mental function varies over the course of the day ( MFV ) , episode of disorganised speech ( EDS ) , and easily distracted ( ED ) . Geriatricians assessed subjects face to face within 4 hours of nurses ’ assessment using the Diagnostic and Statistical Manual of Mental Disorders ( DSM IV ) criteria and clinical judgement to determine delirium presence . Based on the performance of each delirium feature and to achieve highest predictive accuracy , a combination algorithm of either ACMS or MFV was developed and compared with the reference st and ard diagnosis determined by geriatricians . Geriatricians diagnosed delirium in 52 of 239 ( 21.7 % ) subjects aged 70–102 years . The area under the receiver operator characteristics ( AUC ) for interRAI-AC delirium screener algorithm was 0.87 ( 95 % CI ; 0.80 , 0.93 ) , sensitivity 82 % , specificity 91 % , positive and negative predictive value of 0.72 % and 95 % , and likelihood ratio of 9.6 achieving the highest predictive accuracy of all possible combination of 4 delirium features . Underlying pre-morbid cognitive impairment did not undermine validity of the screening strategy , AUC 0.85 ( 95 % CI ; 0.74,0.95 ) , sensitivity 90 % and specificity 69 % . The interRAI AC delirium screening strategy is a valid measure of delirium in older subjects in acute medical wards BACKGROUND Current literature does not identify the significance of underlying cognitive impairment and delirium in older adults during and 30 days following acute care hospitalization . OBJECTIVE Describe the incidence , risk factors , and outcomes associated with incident delirium superimposed on dementia . DESIGN A 24-month prospect i ve cohort study . SETTING Community hospital . PATIENTS A total of 139 older adults ( > 65 years ) with dementia . METHODS This prospect i ve study followed patients daily during hospitalization and 1 month posthospital . Main measures included dementia ( Modified Blessed Dementia Rating score , Informant Question naire on Cognitive Decline in the Elderly ) , daily mental status change , dementia stage/severity ( Clinical Dementia Rating , Global Deterioration Scale ) , delirium ( Confusion Assessment Method ) , and delirium severity ( Delirium Rating Scale-Revised-98 ) . All statistical analysis was performed using SAS 9.3 , and significance was an α level of 0.05 . Logistic regression , analysis of covariance , or linear regression was performed controlling for age , gender , and dementia stage . RESULTS The overall incidence of new delirium was 32 % ( 44/139 ) . Those with delirium had a 25 % short-term mortality rate , increased length of stay , and poorer function at discharge . At 1 month follow-up , subjects with delirium had greater functional decline . Males were more likely to develop delirium , and for every 1 unit increase in dementia severity ( Global Deterioration Scale ) , subjects were 1.5 times more likely to develop delirium . CONCLUSIONS Delirium prolongs hospitalization for persons with dementia . Thus , interventions to increase early detection of delirium have the potential to decrease the severity and duration of delirium and to prevent unnecessary suffering and costs from the complications of delirium and unnecessary readmissions to the hospital OBJECTIVES Because delirium is a common yet frequently unrecognized condition , this study sought to design a brief screening tool for a core feature of mental status and to vali date the instrument as a serial assessment for delirium . DESIGN Prospect i ve cohort study . SETTING Tertiary VA Hospital in New Engl and . PARTICIPANTS A total of 95 veterans admitted to the medical service . METHODS A consensus panel developed a modified version of the Richmond Agitation and Sedation Scale ( RASS ) to capture alterations in consciousness . Upon admission , and daily thereafter , patients were screened with a modified RASS ( mRASS ) and independently underwent a comprehensive mental status interview by a geriatric expert , who determined whether the criteria for delirium were met . The sensitivity , specificity , and positive likelihood ratio ( LR ) of the mRASS for delirium are reported . RESULTS As a single assessment , the mRASS had a sensitivity of 64 % and a specificity of 93 % for delirium ( LR , 9.4 ) . When used to detect change , serial mRASS assessment s had a sensitivity of 74 % and a specificity of 92 % ( LR , 8.9 ) in both prevalent and incident delirium . When prevalent cases were excluded , any change in the mRASS had a sensitivity of 85 % and a specificity of 92 % for incident delirium ( LR , 10.2 ) CONCLUSION When administered daily , the mRASS has good sensitivity and specificity for incident delirium . Given the brevity of the instrument ( < 30 seconds ) , consideration should be given to incorporating the modified RASS as a daily screening measure for consciousness and delirium The Delirium Observation Screening ( DOS ) scale , a 25-item scale , was developed to facilitate early recognition of delirium , according to the Diagnostic and Statistical Manual-IV criteria , based on nurses ' observations during regular care . The scale was tested for content validity by a group of seven experts in the field of delirium . Internal consistency , predictive validity , and concurrent and construct validity were tested in two prospect i ve studies with high risk groups of patients : geriatric medicine patients and elderly hip fracture patients . Among the patients admitted to a geriatric department ( N = 82 ) , 4 became delirious ; among the elderly hip fracture patients ( N = 92 ) , 18 became delirious . The DOS scale was determined to be content valid and showed high internal consistency , alpha = 0.93 and alpha = 0.96 . Predictive validity against the Diagnostic and Statistical Manual-IV diagnosis of delirium made by a geriatrician was good in both studies . Correlations of the DOS scale with the Mini Mental State Examination ( MMSE ) were Rs -0.79 ( p < or = 0.001 ) in the hip fracture patients and Rs -0.66 ( p < or = 0.001 ) in the geriatric medicine patients . Concurrent validity , as tested by comparison of the research nurse 's ratings of the DOS scale and the Confusion Assessment Method ( CAM ) , for the group of hip fracture patients was 0.63 ( p < or = 0.001 ) . Construct validity of the DOS was tested against the Informant Question naire of Cognitive Decline in Elderly ( IQCODE ) , a preexisting psychiatric diagnosis and the Barthel Index . Correlation with the IQCODE was 0.74 ( p < or = 0.001 ) in the study with the hip fracture patients and 0.33 ( p < or = 0.05 ) in the study with the geriatric medicine patients . Correlation with the Barthel Index was -0.26 ( p < or = 0.05 ) in the geriatric medicine patients and -0.55 ( p < or = 0.001 ) in the hip fracture patients . The overall conclusion of these studies is that the DOS scale shows satisfactory validity and reliability , to guide early recognition of delirium by nurses ' observation STUDY OBJECTIVE Delirium is a common form of acute brain dysfunction with prognostic significance . Health care professionals caring for older emergency department ( ED ) patients miss delirium in approximately 75 % of cases . This error results from a lack of available measures that can be performed rapidly enough to be incorporated into clinical practice . Therefore , we developed and evaluated a novel 2-step approach to delirium surveillance for the ED . METHODS This prospect i ve observational study was conducted at an academic ED in patients aged 65 years or older . A research assistant and physician performed the Delirium Triage Screen ( DTS ) , design ed to be a highly sensitive rule-out test , and the Brief Confusion Assessment Method ( bCAM ) , design ed to be a highly specific rule-in test for delirium . The reference st and ard for delirium was a comprehensive psychiatrist assessment using Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision criteria . All assessment s were independently conducted within 3 hours of one another . Sensitivities , specificities , and likelihood ratios with their 95 % confidence intervals ( 95 % CIs ) were calculated . RESULTS Of 406 enrolled patients , 50 ( 12.3 % ) had delirium diagnosed by the psychiatrist reference st and ard . The DTS was 98.0 % sensitive ( 95 % CI 89.5 % to 99.5 % ) , with an expected specificity of approximately 55 % for both raters . The DTS 's negative likelihood ratio was 0.04 ( 95 % CI 0.01 to 0.25 ) for both raters . As the complement , the bCAM had a specificity of 95.8 % ( 95 % CI 93.2 % to 97.4 % ) and 96.9 % ( 95 % CI 94.6 % to 98.3 % ) and a sensitivity of 84.0 % ( 95 % CI 71.5 % to 91.7 % ) and 78.0 % ( 95 % CI 64.8 % to 87.2 % ) when performed by the physician and research assistant , respectively . The positive likelihood ratios for the bCAM were 19.9 ( 95 % CI 12.0 to 33.2 ) and 25.2 ( 95 % CI 13.9 to 46.0 ) , respectively . If the research assistant DTS was followed by the physician bCAM , the sensitivity of this combination was 84.0 % ( 95 % CI 71.5 % to 91.7 % ) and specificity was 95.8 % ( 95 % CI 93.2 % to 97.4 % ) . If the research assistant performed both the DTS and bCAM , this combination was 78.0 % sensitive ( 95 % CI 64.8 % to 87.2 % ) and 97.2 % specific ( 95 % CI 94.9 % to 98.5 % ) . If the physician performed both the DTS and bCAM , this combination was 82.0 % sensitive ( 95 % CI 69.2 % to 90.2 % ) and 95.8 % specific ( 95 % CI 93.2 % to 97.4 % ) . CONCLUSION In older ED patients , this 2-step approach ( highly sensitive DTS followed by highly specific bCAM ) may enable health care professionals , regardless of clinical background , to efficiently screen for delirium . Larger , multicenter trials are needed to confirm these findings and to determine the effect of these assessment s on delirium recognition in the ED PURPOSE Previous studies investigating adverse outcomes of hospitalized elders have focused on community-dwelling patients . Given the rapid growth of population s living in other setting s , such as assisted living facilities , it is important to underst and whether these patients are at higher risk of experiencing specific adverse outcomes during hospitalization , so that interventions can be developed to reduce risk . METHODS This is a prospect i ve , observational study of 212 sequential patients admitted during a 1-month period in 2006 to a 38-bed Acute Care for Elders unit in Rochester , New York and followed until discharge . We categorized the patients by residence prior to admission ( i.e. , community , assisted living , and nursing home ) . Our outcome categories were : worsening function , delirium , depression , falls , pressure sores , and nursing home admission . RESULTS After adjusting for multiple characteristics , we found that patients admitted from assisted living facilities were at substantially higher risk than those admitted from the community for functional decline and falls . Patients from nursing homes had a trend toward increased risk for these outcomes , but the trend did not reach statistical significance . More than three fourths of assisted living facility residents were discharged to a nursing home after hospitalization , with a relative risk of 9.41 ( p < .001 ) versus community-dwellers for this outcome . IMPLICATION S People who are admitted to the hospital from assisted living facilities are at high risk for falls and functional decline during hospitalization . Assisted living residents are at a particularly high risk of nursing home admission following hospitalization . Targeted preventive programs should be developed with a goal of reducing risk in this vulnerable population BACKGROUND Delirium is a common , yet frequently under-recognized medical/psychiatric complication for hospitalized patients , associated with substantial morbidity and mortality . While easy-to-use delirium screening tools exist for ventilated patients , their use in non-critically ill , hospitalized patients has not been vali date d. METHODS This prospect i ve 4-week comparison of daily delirium status , using screening tools ( Confusion Assessment Method for the Intensive Care Unit [ CAM-ICU ] and Intensive Care Delirium Screening Checklist [ ICDSC ] ) vs. a daily neuropsychiatric examination as a reference st and ard , was conducted in 139 in patients in two medical oncology units at a large teaching hospital during July , 2009 . RESULTS Based on neuropsychiatric examination , 36 ( 26 % ) patients had at least 1 day of delirium during their hospital admission . For 21 ( 15 % ) patients , delirium was present at the initial assessment , while 15 ( 11 % ) developed delirium at a median ( IQR ) of three ( 2 - 7 ) subsequent assessment s. Delirium was present on 20 % of all patient-days . For the initial evaluation , the CAM-ICU had a sensitivity of 18 % ( 95 % confidence interval [ CI ] , 5%-44 % ) , and a sensitivity of 18 % ( 9 % -32 % ) when using all assessment s , adjusting for repeated measures on each patient . The ICDSC had sensitivities of 47 % ( 24%-72 % ) and 62 % ( 49%-74 % ) . The specificity of both instruments was very high ( ≥98 % ) . CONCLUSIONS This study suggests that in non-critically ill hospitalized patients , the CAM-ICU and ICDSC intensive care delirium screening tools are not adequately sensitive for use in routine clinical practice . Further work is needed to develop more sensitive , efficient tools in this population Because no rigorously vali date d , simple yet accurate continuous delirium assessment instrument exists , we developed the Nursing Delirium Screening Scale ( Nu-DESC ) . The Nu-DESC is an observational five-item scale that can be completed quickly . To test the validity of the Nu-DESC , 146 consecutive hospitalized patients from a prospect i ve cohort study were continuously assessed for delirium symptoms by bedside nurses using the Nu-DESC . Psychometric properties of Nu-DESC screening were established using 59 blinded Confusion Assessment Method ( CAM ) ratings made by research nurses and psychiatrists . DSM-IV criteria and the Memorial Delirium Assessment Scale ( MDAS ) were rated along with CAM assessment s. Analysis of these data showed that the Nu-DESC is psychometrically valid and has a sensitivity and specificity of 85.7 % and 86.8 % , respectively . These values are comparable to those of the MDAS , a longer instrument . Nu-DESC and DSM-IV sensitivities were similar . The Nu-DESC appears to be well-suited for widespread clinical use in busy oncology inpatient setting s and shows promise as a research instrument |
2,103 | 22,942,327 | Overall , the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo ( at 24 hours , 1 week , or 2 weeks ) or in addition to nonsteroidal antiiflammatory drugs ( at 24 hours ) on pain intensity , function , or quality of life .
Based upon the currently available evidence in patients with IA , benzodiazepines ( diazepam and triazolam ) do not appear to be beneficial in improving pain over 24 hours or 1 week .
The non-benzodiazepine agent zopiclone also did not significantly reduce pain over 2 weeks .
However , even short-term muscle relaxant use ( 24 hours to 2 weeks ) is associated with significant adverse events , predominantly drowsiness and dizziness | OBJECTIVE To determine the efficacy and safety of muscle relaxants in pain management in patients with inflammatory arthritis ( IA ) . | Sleep disturbances and related daytime complaints are frequent in rheumatoid arthritis ( RA ) . The aim of the current study was therefore to evaluate the effect of a newer hypnotic on sleep structure and clinical parameters in RA . Forty out patients were r and omized to a two week treatment regimen with either 7.5 mg zopiclone or placebo at bedtime . Clinical examinations were performed before and after treatment and the degree of pain , fatigue , sleepiness , morning stiffness , and activities of daily living were assessed . Two sleep question naires were also completed weekly . Polysomnography was performed before the study and after 14 days of treatment . Recordings were evaluated using conventional sleep scoring as well as frequency analysis of the electroencephalography ( EEG ) . Patients in the zopiclone group had subjective improvement of sleep , but otherwise no differences in pain score or the other clinical parameters were found . Conventional sleep assessment s showed only minor changes during treatment , but frequency analysis demonstrated a shift from the lower towards the higher EEG frequencies in the active treatment group . Although the modulation of the EEG can represent a non-specific pharmacologic epiphenomenon , it might also reflect a disturbance of sleep microstructure . In conclusion , treatment with zopiclone may be of value for subjective sleep complaints in selected patients with RA , but it is doubtful whether hypnotics improve daytime symptoms in this patient group The efficacy of indomethacin 100 mg , diazepam 10 mg , and placebo in producing sleep , relieving night pain , and reducing the severity of morning stiffness , was compared in 18 patients in hospital with active classical or definite rheumatoid arthritis . There was no statistically significant difference in the preference of patients or sleep score among the three forms of treatment . Both indomethacin and diazepam were more effective than placebo in relieving night pain . Indomethacin decreased , but diazepam increased , morning stiffness in comparison to placebo . Neither active therapy produced significant side-effects A double-blind controlled trial was carried out in 18 in- patients with classical or definite rheumatoid arthritis to assess the effectiveness of night-time medication with 100 mg indomethacin plus 10 mg diazepam , 200 mg sulindac , and 200 mg sulindac plus 10 mg diazepam in improving sleep and reducing night pain and the duration of morning stiffness . Patients received each treatment regimen for 1 night . The results from the 17 patients completing the full trial protocol indicated that indomethacin plus diazepam was the most effective of the three regimens , although the differences did not reach conventional statistical significance . It is suggested that in further such studies with sulindac a larger dose and a longer duration of treatment should be used Seventeen of eighteen patients hospitalized for active rheumatoid arthritis completed a three-day r and omized , double-blind comparison of 100 mg indomethacin , 100 mg indomethacin with 10 mg diazepam and matching placebo as night medication . The results showed a consistent pattern in the four functions measured -- pain , morning stiffness , sleep score and patient preference . In each , indomethacin proved superior to placebo and the combined therapy better than indomethacin alone . From this it has been concluded that the combination of indomethacin and diazepam should now be considered the treatment of choice for maximum control of night pain and morning stiffness in rheumatoid arthritis OBJECTIVE To evaluate the effects of triazolam upon insomnia and daytime sleepiness in patients with rheumatoid arthritis ( RA ) . METHODS Triazolam or placebo was administered during two 7 night periods to 15 patients with RA in a double blind crossover study . Polysomnographic recordings were conducted on the last 2 nights of each condition , and multiple sleep latency tests and mood and arthritis assessment s were performed during the intervening day in each condition . RESULTS In the triazolam condition , total sleep time was increased , daytime sleepiness was reduced , and morning stiffness was improved compared to placebo . Objective measures of sleep fragmentation were unchanged . Clinical arthritis assessment s were similar during both conditions . CONCLUSION Short term hypnotic therapy improves sleep in patients with RA and appears to improve morning stiffness and daytime sleepiness |
2,104 | 31,749,986 | Two Cochrane systematic literature review s ( SLRs ) have reported that topical treatments for dry mouth and dry eye are safe and effective .
RCTs using infliximab , anakinra and baminercept found no placebo-differences for the primary outcomes .
Conclusion The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid , while limited data from RCTs are available to guide systemic therapies | Objective To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome ( SjS ) to inform European League Against Rheumatism treatment recommendations . | The effect of hydroxychloroquine ( HCQ ) on dry eye has not been fully determined . This study aim ed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren 's syndrome ( pSS ) . A double-blind , r and omized control study was conducted in 39 pSS subjects from May 2011 through August 2013 . pSS was diagnosed based on the classification criteria of the American-European Consensus Group . Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline , 6 , and 12 weeks , with a re-visit at 16 weeks after drug discontinuance . The fluorescein staining score , Schirmer test score , tear film break-up time ( TBUT ) , and ocular surface disease index ( OSDI ) were measured , and tears and blood were collected for ESR , IL-6 , IL-17 , B-cell activating factor ( BAFF ) , and Th17 cell analysis . Color testing was performed and the fundus was examined to monitor HCQ complications . Twenty-six subjects completed the follow-up . The fluorescein staining score and Schirmer test score did not differ significantly . The OSDI improved with medication in the HCQ group but was not significantly different between the groups . TBUT , serum IL-6 , ESR , serum and tear BAFF , and the proportion of Th17 cells did not change in either group . HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS ( Clinical Trials.gov . NCT01601028 ) OBJECTIVE There is evidence to support a dominant role for B cells in the pathophysiology of primary Sjögren 's syndrome ( SS ) . Therefore , we evaluated the safety and efficacy of anti-CD20 monoclonal antibody . METHODS Sixteen patients who met the new American-European Consensus Group criteria for primary SS and scored > 50 on at least 2 of 4 visual analog scales ( VAS ; 100 mm ) evaluating global disease , pain , fatigue , and global dryness received infusions of low-dose rituximab ( 375 mg/m(2 ) ) at weeks 0 and 1 without steroid premedication . RESULTS Slow rituximab infusions ( 100 mg/hour ) were well tolerated , with only 1 patient experiencing serum sickness-like disease . There was a dramatic reduction in B cells of the blood and salivary gl and ( SG ) . At week 12 , VAS scores with respect to fatigue and dryness ( P < 0.05 ) , tender point count ( P < 0.035 ) , and quality of life as evaluated by the Short Form 36 question naire ( SF-36 ; P < 0.001 ) were significantly improved . At week 36 , significant improvements were noted in the 4 VAS scores ( P < 0.05 ) , tender joint count ( P = 0.017 ) , tender point count ( P = 0.027 ) , and SF-36 ( P < 0.03 ) . Pulmonary manifestations were ameliorated in 1 patient . Patients with improvements on at least 3 of the 4 VAS scores at any visit ( n = 11 ) had a shorter disease duration than the other patients ( n = 5 ; mean + /- SD duration 3.8 + /- 5.4 versus 30.1 + /- 29.5 years ; P = 0.02 ) . CONCLUSION Low-dose rituximab infusions were well tolerated without the benefit of steroids . Infusions induced a rapid depletion of B cells in the blood and SG and could improve primary SS . Controlled studies are needed The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium ( MPS ) in patients with primary Sjögren syndrome ( pSS ) refractory to other immunosuppressive agents . Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center , open-label pilot trial . At baseline , after 3 months , and after 6 months , we examined the clinical status , including gl and ular function tests , as well as different laboratory parameters associated with pSS . In addition , subjective parameters were determined on the basis of different question naires . Treatment with MPS was well tolerated in 8 of 11 patients . Due to vertigo or gastrointestinal discomfort , two patients did not complete the trial . One patient developed pneumonia 2 weeks after treatment and was withdrawn . In the remaining patients , MPS treatment result ed in subjective improvement of ocular dryness on a visual analogue scale and a reduced dem and for artificial tear supplementations . However , no significant alterations of objective parameters for dryness of eyes and mouth were observed , although a substantial improvement of gl and ular functions occurred in two patients with short disease duration . In addition , treatment with MPS result ed in significant reduction of hypergammaglobulinemia and rheumatoid factors as well as an increase of complement levels and white blood cells . MPS promises to be an additional therapeutic option for patients with pSS , at least in those with shorter disease duration . Further investigations about the efficacy and safety of MPS in pSS have to be performed in larger numbers of patients Objectives Fatigue is a major cause of disability in primary Sjögren 's syndrome ( pSS ) . Fatigue has similarities with sickness behaviour in animals ; the latter mediated by pro-inflammatory cytokines , in particular interleukin (IL)-1 , acting on neuronal brain cells . We hypothesised that IL-1 inhibition might improve fatigue in pSS patients ; thus , we examined the effects and safety of an IL-1 receptor antagonist ( anakinra ) on fatigue . Methods Twenty-six pSS patients participated in a double-blind , placebo-controlled parallel group study . Patients were r and omised to receive either anakinra or a placebo for four weeks . Fatigue was evaluated by a fatigue visual analogue scale and the Fatigue Severity Scale . The primary outcome measure was a group-wise comparison of the fatigue scores at week 4 , adjusted for baseline values . Secondary outcome measures included evaluation of laboratory results and safety . The proportion of patients in each group who experienced a 50 % reduction in fatigue was regarded as a post-hoc outcome . All outcomes were measured at week 4 . Results There was no significant difference between the groups in fatigue scores at week 4 compared to baseline after treatment with anakinra . However , six out of 12 patients on anakinra versus one out of 13 patients on the placebo reported a 50 % reduction in fatigue VAS ( p = 0.03 ) . There were two serious adverse events in each group . Conclusions This r and omised , double-blind , placebo-controlled trial of IL-1 blockade did not find a significant reduction in fatigue in pSS in its primary endpoint . A 50 % reduction in fatigue was analysed post-hoc , and significantly more patients on the active drug than on placebo reached this endpoint . Although not supported by the primary endpoint , this may indicate that IL-1 inhibition influences fatigue in patients with pSS . Trial registration Clinical Trials.gov BACKGROUND Primary Sjögren syndrome ( pSS ) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations . OBJECTIVE To evaluate efficacy and harms of rituximab in adults with recent-onset or systemic pSS . DESIGN R and omized , placebo-controlled , parallel-group trial conducted between March 2008 and January 2011 . Study personnel ( except pharmacists ) , investigators , and patients were blinded to treatment group . ( Clinical Trials.gov : NCT00740948 ) . SETTING 14 university hospitals in France . PATIENTS 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales ( VASs ) ( global disease , pain , fatigue , and dryness ) and recent-onset ( < 10 years ) biologically active or systemic pSS . INTERVENTION R and omization ( 1:1 ratio ) to rituximab ( 1 g at weeks 0 and 2 ) or placebo . MEASUREMENTS Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24 . RESULTS No significant difference between groups in the primary end point was found ( difference , 1.0 % [ 95 % CI , -16.7 % to 18.7 % ] ) . The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 ( 22.4 % vs. 9.1 % ; P = 0.036 ) . An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 ( P < 0.001 ) and 16 ( P = 0.012 ) , and improvement in fatigue from baseline to week 24 was greater with rituximab . Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab . LIMITATION Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinical ly important changes . CONCLUSION Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24 , although it alleviated some symptoms at earlier time points OBJECTIVE To study the efficacy and safety of B cell depletion with rituximab , a chimeric murine/human anti-CD20 monoclonal antibody , in patients with primary Sjögren 's syndrome ( SS ) in a double-blind , r and omized , placebo-controlled trial . METHODS Patients with active primary SS , as determined by the revised American-European Consensus Group criteria , and a rate of stimulated whole saliva secretion of > or = 0.15 ml/minute were treated with either rituximab ( 1,000 mg ) or placebo infusions on days 1 and 15 . Patients were assigned r and omly to a treatment group in a ratio of 2:1 ( rituximab : placebo ) . Followup was conducted at 5 , 12 , 24 , 36 , and 48 weeks . The primary end point was the stimulated whole saliva flow rate , while secondary end points included functional , laboratory , and subjective variables . RESULTS Thirty patients with primary SS ( 29 female ) were r and omly allocated to a treatment group . The mean + /- SD age of the patients receiving rituximab was 43 + /- 11 years and the disease duration was 63 + /- 50 months , while patients in the placebo group were age 43 + /- 17 years and had a disease duration of 67 + /- 63 months . In the rituximab group , significant improvements , in terms of the mean change from baseline compared with that in the placebo group , were found for the primary end point of the stimulated whole saliva flow rate ( P = 0.038 versus placebo ) and also for various laboratory parameters ( B cell and rheumatoid factor [ RF ] levels ) , subjective parameters ( Multidimensional Fatigue Inventory [ MFI ] scores and visual analog scale [ VAS ] scores for sicca symptoms ) , and extragl and ular manifestations . Moreover , in comparison with baseline values , rituximab treatment significantly improved the stimulated whole saliva flow rate ( P = 0.004 ) and several other variables ( e.g. , B cell and RF levels , unstimulated whole saliva flow rate , lacrimal gl and function on the lissamine green test , MFI scores , Short Form 36 health survey scores , and VAS scores for sicca symptoms ) . One patient in the rituximab group developed mild serum sickness-like disease . CONCLUSION These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS OBJECTIVE To report the efficacy and safety of long-term treatment of SS with belimumab , targeting the B-cell-activating factor . METHODS Patients with primary SS were included in the BELISS open-label phase II study , a 1-year open-label trial , if they were positive for anti-SSA or anti-SSB antibodies and had systemic complications or persistent salivary gl and enlargement or early disease or biomarkers of B-cell activation . They received belimumab , 10 mg/kg i.v . , at weeks 0 , 2 and 4 and then every 4 weeks ; if response was observed at week 28 , or if the clinician and the patient agreed to continue the study in the absence of side effects , treatment was continued for 1 year . Efficacy and safety were analysed during the 1-year period of treatment . RESULTS Among the 30 patients recruited , 28 were evaluated at week 28 as already reported . Nineteen terminated the 52-week study , 15 of them being responders and 4 non-responders at week 28 . Thirteen of the 15 responders at week 28 also responded at week 52 ( 86.7 % ) . The improvement in the EULAR Sjögren 's Syndrome Disease Activity Index and EULAR Sjögren 's Syndrome Patient Reported Index scores observed at week 28 showed a trend to further improvement at week 52 , and the amelioration of peculiar EULAR Sjögren 's Syndrome Disease Activity Index domains ( gl and ular , lymphadenopathy , articular ) appeared of particular relevance . The decrease in biomarkers of B-cell activation observed at week 28 persisted unchanged until week 52 , with RF decreasing further . Salivary flow , Schirmer 's test and the focus score of salivary biopsy did not change . Safety of treatment was good . CONCLUSION Long-term treatment with belimumab may be beneficial in SS . R and omized , double-blind , controlled studies in larger population s are encouraged This open-label , phase I/II study investigated the safety and efficacy of epratuzumab , a humanised anti-CD22 monoclonal antibody , in the treatment of patients with active primary Sjögren 's syndrome ( pSS ) . Sixteen Caucasian patients ( 14 females/2 males , 33–72 years ) were to receive 4 infusions of 360 mg/m2 epratuzumab once every 2 weeks , with 6 months of follow-up . A composite endpoint involving the Schirmer-I test , unstimulated whole salivary flow , fatigue , erythrocyte sedimentation rate ( ESR ) , and immunoglobulin G ( IgG ) was devised to provide a clinical ly meaningful assessment of response , defined as a ≥20 % improvement in at least two of the aforementioned parameters , with ≥20 % reduction in ESR and /or IgG considered as a single combined criterion . Fourteen patients received all infusions without significant reactions , 1 patient received 3 , and another was discontinued due to a mild acute reaction after receiving a partial infusion . Three patients showed moderately elevated levels of Human anti-human ( epratuzumab ) antibody not associated with clinical manifestations . B-cell levels had mean reductions of 54 % and 39 % at 6 and 18 weeks , respectively , but T-cell levels , immunoglobulins , and routine safety laboratory tests did not change significantly . Fifty-three percent achieved a clinical response ( at ≥20 % improvement level ) at 6 weeks , with 53 % , 47 % , and 67 % responding at 10 , 18 , and 32 weeks , respectively . Approximately 40%–50 % responded at the ≥30 % level , while 10%–45 % responded at the ≥50 % level for 10–32 weeks . Additionally , statistically significant improvements were observed in fatigue , and patient and physician global assessment s. Further , we determined that pSS patients have a CD22 over-expression in their peripheral B cells , which was downregulated by epratuzumab for at least 12 weeks after the therapy . Thus , epratuzumab appears to be a promising therapy in active pSS , suggesting that further studies be conducted Abstract The purpose of the study was to evaluate the efficacy of an ophthalmic solution containing 0.1 % fluorometholone ( FML ) and 0.1 % sodium hyaluronate ( HA ) for the treatment of ocular dryness in Sjögren syndrome ( SS ) patients .Forty SS patients were r and omly assigned to the FML or cyclosporin A ( CsA ) treatment groups . The FML group was treated with 0.1 % FML and 0.1 % HA , and the CsA group was treated with 0.5 % CsA and 0.1 % HA . Primary outcomes were corneal fluorescein staining ( CFS ) , the Ocular Surface Disease Index ( OSDI ) score , conjunctival goblet cell density , and the severity of conjunctival congestion . Patients were also evaluated based on tear film breakup time ( TFBUT ) and the Schirmer test . After 8 weeks of treatment , the mean CFS scores were significantly lower in both the groups , compared with the baseline values , and the CFS score of the FML group at week 2 was significantly lower than that of the CsA group ( P = 0.042 ) . The OSDI scores improved significantly in both the groups throughout the study , and the OSDI score in the FML group at week 4 was significantly lower than that of the CsA group ( P = 0.042 ) . After 8 weeks of therapy , the conjunctival goblet cell density was significantly higher in both the groups ( P < 0.001 for both ) compared with the baseline values . Conjunctival congestion was reduced in both the groups throughout the study , and the severity in the FML group was significantly less at week 4 compared with that in the CsA group ( P = 0.035 ) . The TFBUT in the FML group at week 8 was significantly longer than in the CsA group ( P = 0.04).Treatment using topical 0.1 % FML provided faster improvement in the symptoms of ocular dryness in SS patients compared with topical 0.5 % OBJECTIVE To evaluate cyclosporine 0.1 % ophthalmic emulsion over a 1- to 3-year period in moderate to severe dry eye disease patients . DESIGN Nonr and omized , multicenter , open-label clinical trial extending 2 ophthalmic cyclosporine phase III clinical trials . PARTICIPANTS Four hundred twelve patients previously dosed for 6 to 12 months with cyclosporine 0.05 % or 0.1 % in prior phase III trials . INTERVENTION Patients instilled ophthalmic cyclosporine 0.1 % twice daily into both eyes for up to 3 consecutive 12-month extension periods . MAIN OUTCOME MEASURES Corneal staining , Schirmer tests , and symptom severity assessment s were conducted during the first 12-month extension , with a patient survey during the second 12-month extension . Biomicroscopy and visual acuity ( VA ) examinations , intraocular pressure ( IOP ) measurements , and adverse effects queries occurred at 6-month intervals . RESULTS Mean duration of treatment was 19.8 months . Improvements in objective and subjective measures of dry eye disease were modest , probably because of prior treatment with cyclosporine . Most survey respondents said their symptoms began to resolve in the first 3 months of cyclosporine treatment during the previous phase III clinical trials . At study exit , VA decreased in 12.6 % ( 93/738 ) and increased in 5.4 % ( 40/738 ) of eyes by > or = 2 lines ; severity of biomicroscopy findings increased in 3.4 % ( chemosis ; 26/760 ) , 7.2 % ( conjunctival hyperemia ; 55/760 ) , or 8.5 % ( tear film debris ; 64/756 ) of eyes ; and mean IOP increased 0.18 mmHg relative to baseline . The most common treatment-related adverse events were burning ( 10.9 % of patients [ 45/412 ] ) , stinging ( 3.9 % [ 16/412 ] ) , and conjunctival hyperemia ( 3.4 % [ 14/412 ] ) . No serious treatment-related adverse events occurred . Most patients ( 95.2 % [ 140/147 ] ) said they would continue cyclosporine therapy ; 97.9 % ( 143/146 ) would recommend it to other dry eye patients . CONCLUSIONS Therapy of chronic dry eye disease with cyclosporine 0.1 % ophthalmic emulsion for 1 to 3 years was safe , well tolerated , and not associated with systemic side effects . The results supplement the safety record of the commercially available cyclosporine 0.05 % ophthalmic emulsion OBJECTIVE To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjögren 's syndrome of short duration ( early primary SS ) and patients with primary SS and mucosa-associated lymphoid tissue (MALT)-type lymphoma ( MALT/ primary SS ) . METHODS Fifteen patients with primary SS were included in this phase II trial . Inclusion criteria for the early primary SS group were B cell hyperactivity ( IgG > 15 gm/liter ) , presence of autoantibodies ( IgM rheumatoid factor , anti-SSA/SSB ) , and short disease duration ( < 4 years ) . Inclusion criteria for the MALT/ primary SS group were primary SS and an associated MALT-type lymphoma ( Ann Arbor stage IE ) localized in the parotid gl and . Patients were treated with 4 infusions of rituximab ( 375 mg/m2 ) given weekly after pretreatment with prednisone ( 25 mg ) and clemastine . Patients were evaluated , using immunologic , salivary/lacrimal function , and subjective parameters , at baseline and at 5 and 12 weeks after the first infusion . RESULTS Significant improvement of subjective symptoms and an increase in salivary gl and function was observed in patients with residual salivary gl and function . Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human anti-chimeric antibodies ( HACAs ) developed in 4 of 15 patients ( 27 % ) , all with early primary SS . Three of these patients developed a serum sickness-like disorder . Of the 7 patients with MALT/ primary SS , complete remission was achieved in 3 , and disease was stable in 3 and progressive in 1 . CONCLUSION Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS . The high incidence of HACAs and associated side effects observed in this study needs further evaluation Objective : Primary Sjögren syndrome ( pSS ) causes significant systemic symptoms including fatigue as well as gl and ular dysfunction . There are currently no effective systemic therapies ; however , open label series have suggested that rituximab may be beneficial for systemic and gl and ular manifestations . Therefore , we performed a double blind , placebo-controlled , r and omised pilot study of the efficacy of rituximab in reducing fatigue in pSS . Methods : A total of 17 patients with pSS and a score on fatigue visual analogue scale ( VAS ) > 50 were r and omised to receive either 2 infusions of rituximab 1 g or placebo ; patients also received oral and intravenous steroids . Outcome measures included : the proportion of patients with > 20 % reduction in fatigue VAS , changes in pSS related symptoms , health related quality of life and immunological parameters of pSS . These were measured 6 months after therapy . Results : There was significant improvement from baseline in fatigue VAS in the rituximab group ( p<0.001 ) in contrast to the placebo group ( p = 0.147 ) . There was a significant difference between the groups at 6 months in the social functioning score of SF-36 ( p = 0.01 ) and a trend to significant difference in the mental health domain score of SF-36 ( p = 0.06 ) . There was one episode of serum sickness in the rituximab treated group . Conclusions : This is the first double blind study of rituximab in pSS to show benefit ; further studies are justified Sjögren syndrome ( SS ) is a chronic inflammatory autoimmune disease of unknown cause whose main characteristic is severe dryness of the eyes and the mouth . The decreased functional capacity of the lacrimal and salivary gl and s which is the result of the inflammatory process and lymphocytic infiltration observed in SS is accountable for this complication . Twenty-nine patients with SS whose ages were ranging between 24–77 , who were under treatment in Ege University Faculty of Medicine Department of Rheumatology , participated in the study , and their informed consents were obtained upon enrollment . Each patient recorded their subjective complaints on a separate question naire . The baseline and subsequent evaluation of the subjective findings on predetermined times ( 1 h after application of the material , at the end of the 1st , 7th , and 14th days ) were also recorded on separate question naire sheets . Throughout the 14-day treatment period , no statistically significant differences were noted between the Xialine ® and placebo groups with regard to burning tongue , diminished taste , and waking up at night to sip water ( p = 0.925 , 0.527 , and 0.066 , respectively ) . However , patients ’ satisfaction with placebo decreased by 25.63 % at the end of the test period , whereas it increased by 16.37 % after Xialine ® administration . Overall , the patients preferred Xialine ® at the end of the study ( p = 0.011 ) . The main motive to administer saliva substitute is to improve lubrication and hydration of oral tissues . The results of this study indicated that Xialine ® is helpful in the management of xerostomia-related symptoms of SS patients . However , further investigations in larger scale group of patients are recommended to provide the effects of these agents on various complaints of xerostomia To compare the effects of treatment with punctal plugs versus artificial tears on visual function for primary Sjögren ’s syndrome with dry eye . Forty-two eyes of 42 patients with primary Sjögren ’s syndrome were enrolled and were allocated r and omly into artificial tears ( AT ) group and punctal plugs ( PP ) group . Ocular Surface Disease Index ( OSDI ) was used , and fluorescent staining for tear film break-up time ( BUT ) , the Schirmer test I ( STI ) and contrast sensitivity was performed before treatment and was repeated 3 months after treatment . A follow-up of 3 months was achieved in 40 eyes of 40 patients , including 19 eyes in artificial tears group and 21 eyes in punctal plugs group . Statistically significant improvements were observed in the OSDI scores ( AT : 52.6 ± 5.7 , 15.9 ± 4.2 ; PP : 55.8 ± 4.9 , 15.1 ± 4.2 ) , corneal fluorescein staining scores ( AT : 2.60 ± 1.76 , 0.30 ± 0.57 ; PP : 1.91 ± 1.60 , 0.09 ± 0.29 ) , STI ( AT : 3.85 ± 2.03 , 8.95 ± 2.72 ; PP : 3.36 ± 1.62 , 11.41 ± 2.65 ) , and BUT ( AT : 2.60 ± 1.39 , 6.00 ± 1.81 ; PP : 2.27 ± 1.12 , 7.82 ± 1.84 ) after treatment compared to those of pre-treatment . The values of STI ( AT : 5.10 ± 1.80 ; PP : 8.05 ± 1.53 ) and BUT ( AT : 3.40 ± 1.31 ; PP : 5.68 ± 1.13 ) in punctal plugs group were significantly more improved than those in the artificial tears group . The medium- and high-level frequencies contrast sensitivities were greatly improved in simulated daylight , night , and glare disability conditions after treatment with artificial tears and punctal plugs . However , the changes in contrast sensitivity did not significantly differ between groups . Both artificial tears and punctal plugs relieved dry eye symptoms , repaired corneal lesions , enhanced tear film stability , and improved contrast sensitivity . Punctal plugs could improve tear film stability and elongate the BUT better than artificial tears OBJECTIVE This pilot study evaluated the effect of anti-tumor necrosis factor-a antiinflammatory treatment with etanercept ( Enbrel(R ) ) on sicca , systemic , and histological signs in patients with primary Sjögren 's syndrome ( SS ) . METHODS Fifteen patients with well defined primary SS were treated with 25 mg etanercept subcutaneously twice per week during 12 weeks , with followup visits at Weeks 18 and 24 . Evaluation measures included a Multidimensional Fatigue Inventory ( MFI ) question naire , serological monitoring , salivary flow tests , Schirmer test , rose bengal cornea staining , and tear film breakup time . A sublabial minor salivary gl and biopsy was performed at baseline and at Week 12 and lymphocytic focus score and percentage IgA-containing plasma cells ( IgA% ) were assessed . RESULTS No increase of salivary or lachrymal gl and function was observed in any participant . In 4 patients a decrease of fatigue complaints was noted , which was also reflected by decreased scores in the MFI question naire . Reduced erythrocyte sedimentation rate was observed in 3 of 4 patients with reduced fatigue . No significant change of lymphocyte focus score or IgA% was observed . A repeated treatment up to 26 weeks showed the same results . CONCLUSION A 12-week or prolonged treatment of etanercept 25 mg twice weekly did not appear to reduce sicca symptoms and signs in SS . However , etanercept treatment may be beneficial in a small subgroup of SS patients with severe fatigue . Etanercept 25 mg twice weekly did not affect minor salivary gl and biopsy results OBJECTIVE To describe the clinical efficacy of the treatment of Sjögren 's syndrome dry eye using 0.03 % tacrolimus eye drop . DESIGN Prospect i ve double-blind r and omized study . SETTING Institutional outpatient clinic . PARTICIPANTS Forty-eight eyes of twenty-four patients with dry eye related to Sjögren syndrome were enrolled in this study . The patients were r and omized in 2 groups : tacrolimus ( n=14 ) and vehicle ( n=10 ) group . INTERVENTION The tacrolimus group received a vial containing tacrolimus 0.03 % ( almond oil as vehicle ) and the other group received the almond oil vehicle . All patients were instructed to use the eye drops every 12h in the lower conjunctival sac . MAIN OUTCOME MEASURES Schirmer I test , break-up-time ( BUT ) , corneal fluorescein and Rose Bengal staining scores were evaluated in all patients one day before the treatment ( baseline ) , 7 , 14 , 28 and 90 days after treatment with the eye drops . RESULTS The average fluorescein and Rose Bengal scores improved statistically after 7 days of treatment and even more after 90 days . The average Schirmer I and BUT values were unchanged after 7 , 14 and 21 days but did show an improvement relative to baseline after 28 days of treatment . Schirmer I , BUT , fluorescein and Rose Bengal did not show any statistical significance in the vehicle group . CONCLUSION Topical 0.03 % tacrolimus eye drop improved tear stability and ocular surface status in cases of inflammatory or SS-related dry eye . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT01850979 OBJECTIVE To study the safety and clinical efficacy of rituximab therapy for primary Sjögren 's syndrome , as well as to investigate its mechanisms . METHODS Patients with primary Sjögren 's syndrome were enrolled in an open-label trial , were given rituximab ( 1 gm ) infusions on days 1 and 15 , and were monitored through week 52 . The primary end point was safety , with secondary end points evaluating clinical and biologic efficacy . Blood was obtained for enumeration of lymphocyte subsets , measurement of serum autoantibody and BAFF levels , and analysis of gene expression . RESULTS Twelve female patients with primary Sjögren 's syndrome were administered rituximab . They had a median age of 51 years ( range 34 - 69 years ) and a median disease duration of 8.0 years ( range 2 - 18 years ) . We observed no unexpected toxicities from the rituximab therapy . Modest improvements were observed at week 26 in patient-reported symptoms of fatigue and oral dryness , with no significant improvement in the objective measures of lacrimal and salivary gl and function . The recovery of blood B cells following the nadir from rituximab therapy was characterized by a predominance of transitional B cells and a lack of memory B cells . While blood B cell depletion was associated with an increase in serum BAFF levels , no significant changes were observed in the levels of serum anti-Ro/SSA , anti-La/SSB , and anti-type 3 muscarinic acetylcholine receptor autoantibodies or in the blood interferon signature . CONCLUSION In patients with primary Sjögren 's syndrome , a single treatment course of rituximab was not associated with any unexpected toxicities and led to only modest clinical benefits despite effective depletion of blood B cells Purpose : To investigate the safety and efficacy of diquafosol tetrasodium , a P2Y2 receptor agonist that stimulates fluid and mucin secretion on the ocular surface , as a novel topical treatment of dry eye disease . Methods : Subjects with dry eye ( n = 527 ) were evaluated in a r and omized , double-masked , parallel-group trial comparing 24 weeks of treatment with 2 concentrations of diquafosol ( 1 % and 2 % ) versus placebo instilled 4 times daily . Corneal staining , conjunctival staining , Schirmer tests , and subjective symptoms of dry eye were evaluated . Use of artificial tears was permitted as necessary . Results : Subjects treated with 2 % diquafosol had significantly lower corneal staining scores compared with placebo at the 6-week , primary efficacy time point ( P < 0.001 ) , and superiority continued throughout the 24-week study . Reductions in corneal staining were observed as early as after 2 weeks of treatment , were maintained throughout the 24-week study , and were observed to worsen slightly ( toward baseline ) when diquafosol treatment was discontinued ( week 25 ) . Results for conjunctival staining were consistent with those observed for corneal staining . Schirmer scores at week 6 were significantly higher with diquafosol treatment than with placebo ( P \H 0.030 ) . The percentage of subjects with clearing of foreign body sensation ( score of 0 ) was higher at week 6 in subjects treated with 2 % diquafosol ( 21 % ) compared with placebo ( 15 % ) , but the difference did not achieve significance ( P = 0.193 ) . Significant differences in favor of diquafosol were observed for clearing of foreign body sensation and for worst symptom in secondary data analyses . Conclusion : Diquafosol tetrasodium was well tolerated and was superior to placebo ( vehicle ) in reducing corneal staining and in relieving certain patient symptoms . Diquafosol has a favorable risk/benefit profile in a broad spectrum of patients with dry eye disease and is a novel topical treatment of dry eye The objective of the study is to investigate the effect of hydroxychloroquine ( HCQ ) on subjective and objective parameters of dry eye in patients with primary Sjogren ’s disease and to evaluate the association of tear fluid B-cell activating factor ( BAFF ) level with the response . Thirty-two patients with primary Sjogren ’s disease were enrolled in this prospect i ve study . All patients included in the study completed at least a 48-month run-in period of using hydroxychloroquine . Patients were then instructed to drop the treatment for 3 months . Baseline and post cessation of treatment ( baseline and 3 months ) evaluations included , subjective symptom scoring , fluorescein and lissamine green staining , Schirmer ’s test , tear break-up time ( BUT ) and tear fluid BAFF assessment s. Significant worsening was observed in , tear break up-time ( TBUT ) ( 7.9 ± 3.4 vs. 5.9 ± 2.9 , P < 0.001 ) lissamine green of staining of the ocular surface ( 1.3 ± 0.9 vs. 1.8 ± 0.8 , P < 0.01 ) and corneal fluorescein staining scores ( 2.2 ± 2.1 vs. 4.6 ± 3.3 , P < 0.003 ) between on and off HCQ treatment , respectively . Similarly , gritty sensation and burning sensation were significantly changed at week 12 compared to baseline evaluation ( 1.18 ± 1.02 vs. 1.7 ± 1.05 , P < 0.007 and 1.1 ± 1.0 vs. 1.6 ± 1.2 , P < 0.0 , respectively ) . Disease duration significantly correlated with baseline OSDI ( r = 0.38 , P < 0.04 ) and the average daily use of artificial tears ( r = 0.36 , P < 0.04 ) . The mean BAFF levels were 0.8 ± 0.5 and 4.0 ± 0.7 ng/ml for baseline and week 12 evaluation , respectively ( P < 0.0001 ) . The results of this study suggest that HCQ may alleviate symptoms and signs of dry eye in pSS and decreases tear fluid BAFF levels The objective of this study was to examine the clinical and immunological factors influencing the efficacy of cevimeline hydrochloride hydrate ( cevimeline ) for the treatment of xerostomia in patients with Sjögren ’s syndrome ( SS ) . Thirty primary SS patients who were medicated with cevimeline were enrolled in this study . Whole stimulated sialometry ( WSS ) was compared between pre- and posttreatment points ( 4 weeks after oral cevimeline administration ) and the increment rate of WSS was calculated . Multiple regression was employed to examine the relative contributions of the clinical and immunological factors , including age , pretreatment WSS , duration of disease , sialography , minor salivary gl and biopsy , anti-Ro/SS-A antibodies , anti-La/SS-B antibodies , and antibodies to muscarinic type 3 receptors to the posttreatment WSS . Patients with normal sialography findings , negative minor salivary gl and biopsy , and absence of anti-La/SS-B antibodies had significantly higher increment rates of WSS compared with those with positive findings ( p = 0.042 , 0.002 , and 0.018 , respectively ) . Results of the multiple regression analysis showed that sialography ( coefficient = −0.867 , p = 0.004 ) and minor salivary gl and biopsy ( coefficient = −0.869 , p = 0.003 ) had significant associations with the posttreatment WSS . Our preliminary results demonstrated the relationship between the effect of cevimeline on saliva secretion and the degree of salivary gl and destruction evaluated by sialography and histopathological findings in the labial minor salivary gl and s. These diagnostic approaches could provide useful prognostic information on the efficacy of cevimeline in SS patients OBJECTIVE To investigate the efficacy , safety , formulation tolerability , and optimal dosing of a novel cyclosporin A oil-in-water emulsion formulation for the treatment of moderate-to-severe dry eye disease . DESIGN R and omized , multicenter , double-masked , parallel-group , dose-response controlled trial . PARTICIPANTS Total enrollment : 162 patients ; cyclosporin A groups : 129 patients ; vehicle group : 33 patients . INTERVENTION Patients instilled study medication ( cyclosporin A ophthalmic emulsion 0.05 % , 0.1 % , 0.2 % , or 0.4 % , or vehicle ) twice daily into both eyes for 12 weeks , followed by a 4-week posttreatment observation period . MAIN OUTCOME MEASURES EFFICACY rose bengal staining , superficial punctate keratitis , Schirmer tear test , symptoms of ocular discomfort , and the Ocular Surface Disease Index ( OSDI ; a measure of symptom frequency and impact on vision-related functioning ) . SAFETY biomicroscopy , cyclosporin A blood levels , conjunctival microbiology , intraocular pressure , visual acuity , and monitoring of adverse events . RESULTS In a subset of 90 patients with moderate-to-severe keratoconjunctivitis sicca , the most significant improvements with cyclosporin A treatment were in rose bengal staining , superficial punctate keratitis , s and y or gritty feeling , dryness , and itching , with improvements persisting into the posttreatment period in some treatment groups . There was also a decrease in OSDI scores , indicating a decrease in the effect of ocular symptoms on patients ' daily lives . There was no clear dose-response relationship , but cyclosporin A 0.1 % produced the most consistent improvement in objective and subjective end points and cyclosporin A 0.05 % gave the most consistent improvement in patient symptoms . The vehicle also performed well , perhaps because of its long residence time on the ocular surface . There were no significant adverse effects , no microbial overgrowth , and no increased risk of ocular infection in any treatment group . The highest cyclosporin A blood concentration detected was 0.16 ng/ml . All treatments were well tolerated by patients . CONCLUSIONS Cyclosporin A ophthalmic emulsions , 0.05 % , 0.1 % , 0.2 % , and 0.4 % , were safe and well tolerated , significantly improved the ocular signs and symptoms of moderate-to-severe dry eye disease , and decreased the effect of the disease on vision-related functioning . Cyclosporin A 0.05 % and 0.1 % were deemed the most appropriate formulations for future clinical studies because no additional benefits were observed with the higher concentrations IMPORTANCE Primary Sjögren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness , pain , and fatigue . Hydroxychloroquine is the most frequently prescribed immunosuppressant for the syndrome . However , evidence regarding its efficacy is limited . OBJECTIVE To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sjögren syndrome : dryness , pain , and fatigue . DESIGN , SETTING , AND PARTICIPANTS From April 2008 to May 2011 , 120 patients with primary Sjögren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were r and omized in a double-blind , parallel-group , placebo-controlled trial . Participants were assessed at baseline , week 12 , week 24 ( primary outcome ) , and week 48 . The last follow-up date for the last patient was May 15 , 2012 . INTERVENTIONS Patients were r and omized ( 1:1 ) to receive hydroxychloroquine ( 400 mg/d ) or placebo until week 24 . All patients were prescribed hydroxychloroquine between weeks 24 and 48 . MAIN OUTCOMES AND MEASURES The primary end point was the proportion of patients with a 30 % or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales ( from 0 [ best ] to 10 [ worst ] ) evaluating dryness , pain , and fatigue . RESULTS At 24 weeks , the proportion of patients meeting the primary end point was 17.9 % ( 10/56 ) in the hydroxychloroquine group and 17.2 % ( 11/64 ) in the placebo group ( odds ratio , 1.01 ; 95 % CI , 0.37 - 2.78 ; P = .98 ) . Between weeks 0 and 24 , the mean ( SD ) numeric analog scale score for dryness changed from 6.38 ( 2.14 ) to 5.85 ( 2.57 ) in the placebo group and 6.53 ( 1.97 ) to 6.22 ( 1.87 ) in the hydroxychloroquine group . The mean ( SD ) numeric analog scale score for pain changed from 4.92 ( 2.94 ) to 5.08 ( 2.48 ) in the placebo group and 5.09 ( 3.06 ) to 4.59 ( 2.90 ) in the hydroxychloroquine group . The mean ( SD ) numeric analog scale for fatigue changed from 6.26 ( 2.27 ) to 5.72 ( 2.38 ) in the placebo group and 6.00 ( 2.52 ) to 5.94 ( 2.40 ) in the hydroxychloroquine group . All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug . Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies , high IgG levels , or systemic involvement . During the first 24 weeks , there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group ; in the last 24 weeks , there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group . CONCLUSIONS AND RELEVANCE Among patients with primary Sjögren syndrome , the use of hydroxychloroquine compared with placebo did not improve symptoms during 24 weeks of treatment . Further studies are needed to evaluate longer-term outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00632866 To prospect ively evaluate histopathologic , blood cellular , serologic , and clinical changes in response to abatacept treatment in patients with primary Sjögren 's syndrome ( SS ) OBJECTIVE To conduct a long-term , prospect i ve , r and omized controlled trial evaluating rituximab ( RTX ) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis ( CV ) . METHODS Fifty-nine patients with CV and related skin ulcers , active glomerulonephritis , or refractory peripheral neuropathy were enrolled . In CV patients who also had hepatitis C virus ( HCV ) infection , treatment of the HCV infection with antiviral agents had previously failed or was not indicated . Patients were r and omized to the non-RTX group ( to receive conventional treatment , consisting of 1 of the following 3 : glucocorticoids ; azathioprine or cyclophosphamide ; or plasmapheresis ) or the RTX group ( to receive 2 infusions of 1 gm each , with a lowering of the glucocorticoid dosage when possible , and with a second course of RTX at relapse ) . Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group . Study duration was 24 months . RESULTS Survival of treatment at 12 months ( i.e. , the proportion of patients who continued taking their initial therapy ) , the primary end point , was statistically higher in the RTX group ( 64.3 % versus 3.5 % [ P < 0.0001 ] ) , as well as at 3 months ( 92.9 % versus 13.8 % [ P < 0.0001 ] ) , 6 months ( 71.4 % versus 3.5 % [ P < 0.0001 ] ) , and 24 months ( 60.7 % versus 3.5 % [ P < 0.0001 ] ) . The Birmingham Vasculitis Activity Score decreased only after treatment with RTX ( from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2 ; P < 0.001 ) up to month 24 ( 4.4 ± 4.6 ; P < 0.0001 ) . RTX appeared to be superior therapy for all 3 target organ manifestations , and it was as effective as conventional therapy . The median duration of response to RTX was 18 months . Overall , RTX treatment was well tolerated . CONCLUSION RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients Objectives To vali date the two recently developed disease activity indexes for assessment of primary Sjögren 's syndrome ( SS ) : the European League Against Rheumatism ( EULAR ) SS Patient Reported Index ( ESSPRI ) and the EULAR SS Disease Activity Index ( ESSDAI ) . Methods A prospect i ve international 6-month duration validation study was conducted in 15 countries . At each visit , physicians completed ESSDAI , SS disease activity index ( SSDAI ) , Sjögren 's Systemic Clinical Activity Index ( SCAI ) and physician global assessment ( PhGA ) ; and patients completed ESSPRI , Sicca Symptoms Inventory ( SSI ) , Profile of Fatigue and Discomfort ( PROFAD ) and patient global assessment ( PGA ) . Psychometric properties ( construct validity , responsiveness and reliability ) were evaluated and compared between scores . Results Of the 395 patients included , 145 ( 37 % ) and 251 ( 64 % ) had currently active or current or past systemic manifestations , respectively . EULAR scores had higher correlation with the gold st and ard than other scores ( ESSDAI with PhGA : r=0.59 ; ESSRPI with PGA : r=0.70 ) . Correlations between patient and systemic scores were very low ( ranging from 0.07 to 0.29 ) . All systemic scores had similar large responsiveness in improved patients . Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD . Reliability was very good for all scores . Conclusions ESSDAI and ESSPRI had good construct validity . All scores were reliable . Systemic scores had a large sensitivity to change in patients whose disease activity improves . Patient scores had a small sensitivity to change , however , significantly better for ESSPRI . Systemic and patient scores poorly correlated , suggesting that they are 2 complementary components that should be both evaluated , but separately OBJECTIVE The objective of this study was to evaluate whether hydroxychloroquine ( HCQ ) therapy effects subjective and /or objective complaints and salivary flow rates of patients with primary Sjögren 's syndrome ( PSS ) . STUDY DESIGN Thirty women recently diagnosed with PSS , scheduled for HCQ treatment ( 400 mg daily ) , participated and were clinical ly examined before initiation of 30 weeks of HCQ treatment . During baseline evaluation , both the objective and /or subjective oral findings were recorded . Unstimulated ( uSFR ) and stimulated salivary flow rates ( sSFR ) were determined . After initiation of HCQ treatment , study parameters were assessed at 6 , 12 , 18 , 24 , and 30 weeks . Each patient served as her own control ; measurements of the baseline and control times were analyzed by ANOVA . RESULTS uSFR values increased significantly with HCQ treatment , but sSFR values , objective and /or subjective complaints did not change considerably . CONCLUSION A positive impact of 30 weeks of HCQ treatment only on uSFRs of SS patients was revealed OBJECTIVE To evaluate the efficacy and safety of an intraoral electrostimulation device , consisting of stimulating electrodes , an electronic circuit , and a power source , in treating xerostomia . The device delivers electrostimulation through the oral mucosa to the lingual nerve in order to enhance the salivary reflex . METHODS The device was tested on a sample of patients with xerostomia due to Sjögren 's syndrome and other sicca conditions in a 2-stage prospect i ve , r and omized , multicenter trial . Stage I was a double-blind , crossover stage design ed to compare the effects of the electrically active device with the sham device , each used for 1 month , and stage II was a 3-month open-label stage design ed to assess the long-term effects of the active device . Improvement in xerostomia severity from baseline was the primary outcome measure . RESULTS A total of 114 patients were r and omized . In stage I , the active device performed better than the sham device for patient-reported xerostomia severity ( P<0.002 ) , xerostomia frequency ( P<0.05 ) , quality of life impairment ( P<0.01 ) , and swallowing difficulty ( P<0.02 ) . At the end of stage II , statistically significant improvements were verified for patient-reported xerostomia severity ( P<0.0001 ) , xerostomia frequency ( P<0.0001 ) , oral discomfort ( P<0.001 ) , speech difficulty ( P<0.02 ) , sleeping difficulty ( P<0.001 ) , and resting salivary flow rate ( P<0.01 ) . CONCLUSION Our findings indicate that daily use of the device alleviated oral dryness , discomfort , and some complications of xerostomia , such as speech and sleeping difficulties , and increased salivary output . The results show a cumulative positive effect of the device over the period of the study , from baseline to the end of the trial Background : For invalidating symptoms in primary Sjögren ’s syndrome ( pSS ) , there is still a need for easy-to-administer , cost-effective and well-tolerated systemic treatment . Leflunomide ( LEF ) is structurally unrelated to other immunomodulatory drugs and might be efficacious in pSS , given its characteristic immunoregulatory modes of action . Objective : To investigate the safety and efficacy of LEF in pSS in a phase II open-label pilot study . Methods : 15 patients with pSS with early and active disease received LEF 20 mg once daily for 24 weeks . Tolerability , safety and efficacy of LEF were evaluated every 8 weeks . Additional safety visits were performed every fortnight . Results : Mild gastrointestinal discomfort ( including diarrhoea ) and hair loss were mainly reported . Five patients developed lupus-like skin lesions on the face , arms or trunk , responding well to topical corticosteroids , nevertheless causing the withdrawal of one patient . Two patients with pre-existing hypertension had to increase dosages of anti-hypertensive drugs . Increased levels of alanine aminotransferase normalised after dose reduction in two patients . A decrease in general fatigue and an increase in physical functioning were observed after 24 weeks . Serum IgG levels decreased from 8 weeks onwards . Schirmer test values increased , not reaching statistical significance , whereas sialometry values did not change . In four of five repeated biopsies , the lymphocytic focus score decreased at the rate of 1 focus/4 mm2 . A remarkable amelioration of leucocytoclastic vasculitis was observed in three patients . Conclusions : Although the safety profile seems fairly acceptable , the observed indications for efficacy were modest and may be doubtful in justifying a r and omised controlled trial of LEF in pSS BACKGROUND Increased expression of B cell activating factor ( BAFF or B lymphocyte stimulator ) may explain the B cell activation characteristic of primary Sjögren 's syndrome ( pSS ) . OBJECTIVES To evaluate the efficacy and safety of belimumab , targeting BAFF , in patients with pSS . METHODS Patients were included in this bi-centric prospect i ve 1-year open-label trial if they fulfilled American European Consensus group criteria , were anti-Sjögren 's syndrome A-positive and had current systemic complications or salivary gl and enlargement , or early disease ( < 5 years ) , or biomarkers of B cell activation . They received belimumab , 10 mg/kg , at weeks 0 , 2 and 4 and then every 4 weeks to week 24 . The primary end-point , assessed at week 28 , was improvement in two of five items : reduction in ≥30 % in dryness score on a visual analogue scale ( VAS ) , ≥30 % in fatigue VAS score , ≥30 % in VAS pain score , ≥30 % in systemic activity VAS assessed by the physician and /or > 25 % improvement in any B cell activation biomarker values . RESULTS Among 30 patients included , the primary end-point was achieved in 18 ( 60 % ) . The mean ( SD ) European League Against Rheumatism ( EULAR ) Sjögren 's Syndrome Disease Activity Index decreased from 8.8 ( 7.4 ) to 6.3 ( 6.6 ) ( p=0.0015 ) and EULAR ) Sjögren 's Syndrome Patient Reported Index from 6.4 ( 1.1 ) to 5.6 ( 2.0 ) ( p=0.0174 ) . The mean dryness , fatigue and pain VAS varied from 7.8 ( 1.8 ) to 6.2 ( 2.9 ) ( p=0.0021 ) , 6.9 ( 1.8 ) to 6.0 ( 2.2 ) ( p=0.0606 ) and 4.6 ( 2.6 ) to 4.7 ( 2.4 ) ( p=0.89 ) , respectively . Salivary flow and Schirmer 's test did not change . CONCLUSIONS These encouraging results justify future r and omised controlled trials of belimumab in a selected target population of pSS patients most likely to benefit from treatment Primary Sjögren 's syndrome is a systemic autoimmune exocrinopathy characterized by a lymphoplasmacytic infiltrate and destruction of salivary and lacrimal gl and ular tissues . There is no widely accepted or effective systemic therapy for this disorder . The purpose of this 6-month r and omized , double-blinded , placebo-controlled study was to examine the effects of prednisone ( 30 mg , alternate days ) , piroxicam ( 20 mg , daily ) , or placebo on the salivary , lacrimal and immunologic alterations of primary Sjögren 's syndrome . Eight patients were enrolled in each group . Salivary and lacrimal function were assessed at entry and at the completion of treatment . Labial minor salivary gl and tissue was obtained at these times and examined for intensity of infiltration ( focus scores ) and for the relative proportion of gl and ular elements . Serologic and subjective evaluations were done as well , and patients were monitored for therapy-related side effects . Neither active treatment led to significant improvement in salivary or lacrimal function , although prednisone improved salivary flow in selected patients and was associated with positive subjective responses . Prednisone also significantly decreased the serum total protein , IgG , IgA , and sedimentation rate and increased the white cell count . There were no significant alterations in either focus scores or the percentage of gl and ular component tissues of minor gl and s with either active treatment . This study demonstrated that 6 months of prednisone or piroxicam at the doses utilized failed to improve the histological or functional parameters of salivary and lacrimal gl and s in primary Sjögren 's syndrome Purpose : To comparatively evaluate the efficacy of a b and age contact lens ( BCL ) and autologous serum ( AS ) eye drops in the management of severe dry eye caused by Sjögren syndrome ( SS ) . Methods : In this prospect i ve r and omized study , 40 patients with SS were enrolled . Patients were divided into 2 treatment groups : BCL and AS . Results : A total of 37 patients were included , 18 patients ( 35 eyes ) in the AS group and 19 patients ( 36 eyes ) in the BCL group . At the end of 6 weeks , the best-corrected visual acuity improved significantly in the BCL group ( 0.5 ± 0.3 vs. 0.3 ± 0.2 , P = 0.003 ) but not in the AS group ( 0.4 ± 0.3 vs. 0.3 ± 0.3 , P = 0.11 ) . The best-corrected visual acuity remained stable up to 6 weeks after discontinuation of the BCL ( 0.5 ± 0.3 vs. 0.4 ± 0.2 , P = 0.03 ) . Although the Ocular Surface Disease Index scores decreased significantly after treatment in both groups , patients in the BCL group had lower Ocular Surface Disease Index scores than those in the AS group ( 53.4 vs. 41.8 at week 3 , 47.1 vs. 31.0 at week 6 , 52.7 vs. 32.0 at week 12 ; P = 0.014 , < 0.001 , < 0.004 , respectively ) . The “ faces ” scores showed improved quality of life in both groups . Tear break-up time improved significantly in both groups except at 6 weeks after discontinuation of the AS . Patients in the BCL group had lower corneal staining scores than those of the AS group after 6 weeks of treatment and 6 weeks after discontinuation of treatment ( P < 0.01 ) . There was no significant change in Schirmer I test scores between or within groups . Conclusions : Balafilcon A silicone hydrogel contact lenses as a BCL were effective in the management of SS-associated dry eye . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT02147509 OBJECTIVE There is no effective treatment for patients with primary Sjögren 's syndrome ( SS ) . Since tumor necrosis factor alpha ( TNF alpha ) could be a key element in the pathogenesis of primary SS , we conducted a multicenter , r and omized , double-blind , placebo-controlled trial to evaluate the effect of infliximab in primary SS . METHODS A total of 103 patients with primary SS were r and omly assigned to receive infliximab infusions ( 5 mg/kg ) or placebo at weeks 0 , 2 , and 6 and were followed up for 22 weeks . All patients fulfilled the new American-European Consensus Group criteria for SS and had active disease as assessed by values > 50 mm on 2 of 3 visual analog scales ( VAS ) ( 0 - 100 mm ) that evaluated joint pain , fatigue , and buccal , ocular , skin , vaginal , or bronchial dryness . A favorable overall response was defined as the patient having > or = 30 % improvement between weeks 0 and 10 in the values on 2 of the 3 VAS . Secondary end points were values on each VAS separately , the number of tender and swollen joints , the basal salivary flow rate , results of the Schirmer test for lacrimal gl and function , the focus score on labial salivary gl and biopsy , the level of C-reactive protein , and the erythrocyte sedimentation rate evaluated at weeks 0 , 10 , and 22 , as well as quality of life evaluated by use of the generic Short Form 36 question naire administered at weeks 0 , 10 , and 22 . RESULTS At week 10 , 26.5 % of patients receiving placebo and 27.8 % of patients treated with infliximab had a favorable overall response ( P = 0.89 ) , and at week 22 , 20.4 % of the placebo group and 16.7 % of the infliximab group had a favorable response ( P = 0.62 ) . In addition , the 2 groups did not differ in any of the secondary end points over the 22 weeks of the trial . Severe adverse events reported in the infliximab group did not differ from those observed in previous studies . CONCLUSION This r and omized , double-blind , placebo-controlled study of an anti-TNF agent did not show any evidence of efficacy of infliximab in primary SS Background : Salivary gl and dysfunction is one of the key manifestations of Sjögren ’s syndrome . Objectives : ( 1 ) To assess prospect ively loss of function of individual salivary gl and s in patients with primary and secondary Sjögren ’s syndrome in relation to disease duration and use of immunomodulatory drugs . ( 2 ) To study changes in sialochemical and laboratory values and subjective complaints over time . Methods : 60 patients with Sjögren ’s syndrome were included in this study . Whole and gl and -specific saliva ( parotid and subm and ibular/sublingual ( SM/SL ) ) , sample s were collected at baseline and after a mean of 3.6 ( SD 2.3 ) years of follow-up . Disease duration was recorded for all patients . Results : Patients with Sjögren ’s syndrome with short disease duration had significantly higher stimulated flow rates at baseline than those with longer disease duration ( p<0.05 ) . When compared with healthy controls , the decrease in SM/SL flow rates at baseline was more prominent than that in parotid flow rates ( p<0.05 ) . Over time , there was a significant further decrease of stimulated flow rates , especially of the parotid gl and , accompanied by increasing problems with swallowing dry food ( p<0.05 ) . The decrease was independent of the use of corticosteroids or disease-modifying antirheumatic drugs ( DMARDs ) . Sialochemical variables remained stable . Conclusions : Early Sjögren ’s syndrome is characterised by a decreased salivary gl and function ( parotis > SM/SL ) , which shows a further decrease over time , regardless of the use of DMARDs or steroids . Patients with Sjögren ’s syndrome with longer disease duration are characterised by severely reduced secretions of both the parotid and SM/SL gl and s. These observations are relevant for identifying patients who would most likely benefit from intervention treatment Aim : To evaluate the effect of oral pilocarpine treatment on conjunctival epithelium of patients with Sjögren ’s syndrome ( SS ) . Methods : 15 primary SS patients were included in this prospect i ve , single masked , comparative study . Patients underwent oral pilocarpine treatment for 2 months and were studied before ( T0 ) and after 1 month ( T1 ) , 2 months ( T2 ) , and 15 days after treatment suspension ( T3 ) . Systemic and ocular symptoms , tear film break up time ( BUT ) , corneal fluorescein vital staining , Schirmer I test , tear basal secretion test , and conjunctival imprinting were performed . Student ’s t test and Mann-Whitney U test were used for statistics . Results : The conjunctival imprinting showed an increase of goblet cells number at T1 ( 1.6 ( 1.2 ) v 0.6 ( 0.7 ) at T0 , p = 0.025 ) improving at T2 ( 5.1 ( 1.7 ) ; p<0.001 v T0 and T1 ) . At T3 the number of goblet cells significantly decreased ( 1.9 ( 1.1 ) ; p<0.001 v T2 ) . An improvement of dry mouth started at T1 and returned towards baseline values at T3 . For ocular symptoms , burning and foreign body sensation were improved at T1 while ocular dryness improved at T2 . BUT showed a statistically significant improvement at T2 . Conclusions : Oral pilocarpine induced an increase in goblet cells number and an amelioration of conjunctival epithelium not dependent on tear secretion OBJECTIVE To assess the safety and potential efficacy of etanercept in the treatment of Sjögren 's syndrome ( SS ) . METHODS This pilot study was a 12-week r and omized , double-blind , placebo-controlled trial of etanercept , with 14 subjects in each group . Patients received 25 mg of etanercept or placebo ( vehicle ) by twice-weekly subcutaneous injection . Patients met the American-European Consensus Group criteria for SS . The primary outcome required at least 20 % improvement from baseline values for at least 2 of the following 3 domains : subjective or objective measures of dry mouth , subjective or objective measures of dry eyes , and IgG level or erythrocyte sedimentation rate ( ESR ) . RESULTS Of the 14 patients taking etanercept , 11 had primary SS and 3 had SS secondary to rheumatoid arthritis . Baseline measures did not differ between the 2 groups . Three etanercept-treated patients and 1 placebo-treated patient did not complete the trial . Five etanercept-treated patients and 3 placebo-treated patients showed improvement from baseline in the primary outcome variable at 12 weeks , but the difference was not statistically significant . There were no significant differences between the groups for changes in subjective measures of oral or ocular symptoms ( by visual analog scale ) , the IgG level , Schirmer I test result , van Bijsterveld score , or salivary flow . At 12 weeks , the ESR had decreased in the etanercept group compared with baseline ( P = 0.004 ) ; however , the mean reduction was only 18.6 % . CONCLUSION We found no evidence to suggest that treatment with etanercept at a dosage of 25 mg twice weekly for 12 weeks was clinical ly efficacious in SS . A larger trial will be necessary to definitively address the efficacy of etanercept in the treatment of SS Objectives To define disease activity levels , minimal clinical ly important improvement ( MCII ) and patient-acceptable symptom state ( PASS ) with the primary Sjögren 's syndrome ( SS ) disease activity indexes : European League Against Rheumatism ( EULAR ) SS disease activity index ( ESSDAI ) and EULAR SS patient-reported index ( ESSPRI ) . Methods For 790 patients from two large prospect i ve cohorts , ESSDAI , physician evaluation of disease activity , ESSPRI and patients ’ satisfaction with their current health status were recorded . Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI . At follow-up visit , patients and physicians assessed , respectively , whether symptoms and disease activity have improved or not . An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI . Results Low-activity ( ESSDAI<5 ) , moderate-activity ( 5≤ESSDAI≤13 ) and high-activity ( ESSDAI≥14 ) levels were defined . MCII of ESSDAI was defined as an improvement of at least three points . The PASS estimate was defined as an ESSPRI<5 points and MCII as a decrease of at least one point or 15 % . Conclusions This study determined disease activity levels , PASS and MCII of ESSDAI and ESSPRI . These results will help design ing future clinical trials in SS . For evaluating systemic complications , the proposal is to include patients with moderate activity ( ESSDAI≥5 ) and define response to treatment as an improvement of ESSDAI at least three points . For addressing patient-reported outcomes , inclusion of patients with unsatisfactory symptom state ( ESSPRI≥5 ) and defining response as an improvement of ESSPRI at least one point or 15 % seems reasonable |
2,105 | 31,996,958 | Because of this mistake , the difference between the artificial and control groups in Figure s6 1.8.1 was not statistically significant ( p = 0.09 ) , thereby failing to support the conclusion that the effect on mortality was more prominent with artificial devices than bio-artificial devices . | null | null |
2,106 | 15,149,313 | RESULTS After adjusting for sample size , study length , and baseline value , there were no statistically significant differences in the ability of either class of calcium antagonist to decrease blood pressure .
Consistently greater reductions in proteinuria were associated with the use of NDCAs compared with DCAs , despite no significant differences in blood pressure reduction or presence of diabetes .
This analysis supports ( 1 ) similar efficacy between subclasses of calcium antagonists to lower blood pressure , and ( 2 ) greater reductions in proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes .
Based on these findings , NDCAs , alone or in combination with an angiotensin-converting enzyme ( ACE ) inhibitor or an angiotensin receptor blocker ( ARB ) , are suggested as preferred agents to lower blood pressure in hypertensive patients with nephropathy associated with proteinuria | BACKGROUND Numerous studies suggest that the dihydropyridine calcium antagonists ( DCAs ) and nondihydropyridine calcium antagonists ( NDCAs ) have differential antiproteinuric effects .
Proteinuria reduction is a correlate of the progression of renal disease .
In an earlier systematic review , calcium antagonists were shown as effective antihypertensive drugs , but there was uncertainty about their renal benefits in patients with proteinuria and renal insufficiency .
METHODS A systematic review was conducted to assess the differential effects of DCAs and NDCAs on proteinuria in hypertensive adults with proteinuria , with or without diabetes , and to determine whether these differential effects translate into altered progression of nephropathy . | CONTEXT Incidence of end-stage renal disease due to hypertension has increased in recent decades , but the optimal strategy for treatment of hypertension to prevent renal failure is unknown , especially among African Americans . OBJECTIVE To compare the effects of an angiotensin-converting enzyme ( ACE ) inhibitor ( ramipril ) , a dihydropyridine calcium channel blocker ( amlodipine ) , and a beta-blocker ( metoprolol ) on hypertensive renal disease progression . DESIGN , SETTING , AND PARTICIPANTS Interim analysis of a r and omized , double-blind , 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( glomerular filtration rate [ GFR ] of 20 - 65 mL/min per 1.73 m(2 ) ) enrolled between February 1995 and September 1998 . This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000 . INTERVENTIONS Participants were r and omly assigned to receive amlodipine , 5 to 10 mg/d ( n = 217 ) , ramipril , 2.5 to 10 mg/d ( n = 436 ) , or metoprolol , 50 to 200 mg/d ( n = 441 ) , with other agents added to achieve 1 of 2 blood pressure goals . MAIN OUTCOME MEASURES The primary outcome measure was the rate of change in GFR ; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50 % or 25 mL/min per 1.73 m(2 ) , end-stage renal disease , or death . RESULTS Among participants with a urinary protein to creatinine ratio of > 0.22 ( corresponding approximately to proteinuria of more than 300 mg/d ) , the ramipril group had a 36 % ( 2.02 [ SE , 0.74 ] mL/min per 1.73 m(2)/y ) slower mean decline in GFR over 3 years ( P = .006 ) and a 48 % reduced risk of the clinical end points vs the amlodipine group ( 95 % confidence interval [ CI ] , 20%-66 % ) . In the entire cohort , there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups ( P = .38 ) . However , compared with the amlodipine group , after adjustment for baseline covariates the ramipril group had a 38 % reduced risk of clinical end points ( 95 % CI , 13%-56 % ) , a 36 % slower mean decline in GFR after 3 months ( P = .002 ) , and less proteinuria ( P<.001 ) . CONCLUSION Ramipril , compared with amlodipine , retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria OBJECTIVE To evaluate the within-trial effect of losartan and conventional antihypertensive therapy ( CT ) compared with placebo and CT on the economic cost associated with end-stage renal disease ( ESRD ) . RESEARCH DESIGN AND METHODS The Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan ( RENAAL ) study was a multinational double-blind r and omized placebo-controlled clinical trial design ed to evaluate the renal protective effects of losartan on a background of CT ( excluding ACE inhibitors and angiotensin II receptor agonists [ AIIAs ] ) in patients with type 2 diabetes and nephropathy . The primary composite end point was doubling of serum creatinine , ESRD , or death . Data on the duration of ESRD were used to estimate the economic benefits of slowing the progression of nephropathy . The cost associated with ESRD was estimated by combining the days each patient experienced ESRD with the cost of ESRD over time . The cost of ESRD for individuals with diabetes was estimated using data from the U.S. Renal Data System . Total cost was estimated as the sum of the cost associated with ESRD and the cost of study therapy . RESULTS -We estimated that losartan and CT compared with placebo and CT reduced the number of days with ESRD by 33.6 per patient over 3.5 years ( P = 0.004 , 95 % CI 10.9 - 56.3 ) . This reduction in ESRD days result ed in a decrease in cost associated with ESRD of 5144 US dollars per patient ( P = 0.003 , 95 % CI 1701 to 8587 US dollars ) . After accounting for the cost of losartan , the reduction in ESRD days result ed in a net savings of 3522 US dollars per patient over 3.5 years ( P = 0.041 , 143 to 6900 US dollars ) . CONCLUSIONS Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the incidence of ESRD , but also result ed in substantial cost savings Objective To investigate in a r and om comparison the capacity of an angiotensin converting enzyme inhibitor ( fosinopril ) , and that of a long-acting dihydropiridine ( nifedipine GITS ) to modify the decay in renal function in patients with primary renal disease , exhibiting a progressive increase in serum creatinine during the previous 2 years . Methods A r and omized , open-label , multicenter study with a minimum follow-up of 3 years . A total of 241 patients were included in the study . All of them were hypertensive and had a 25 % or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study . Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively , and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal ( < 140/90 mmHg ) . Furosemide , atenolol , and doxazosin were added as second , third , and fourth drugs if necessary , for blood pressure control . The primary end-point of the study was the appearance of double the serum creatinine values and /or the need to enter a dialysis programme . Secondary end-points were cardiovascular events , death , changes in 24 h proteinuria , and the evolution of serum creatinine . Data reflect the analysis performed by intention to treat . Results Mean age of the group was 54 ± 14 , and 59 % were males . Primary glomerulonephritis ( 31 % ) , nephrosclerosis ( 26 % ) and polycystic kidney disease ( 19 % ) were the three most frequent diagnostic findings . After 3 years of follow-up , 21 % ( 27/127 ) of patients treated with fosinopril , and 36 % ( 40/112 ) of those receiving nifedipine GITS presented a primary end-point , ( OR 0.47 , 95 % confidence intervals 0.26–0.84 , P = 0.01 ) . Renal survival was significantly better when fosinopril constituted the first step therapy ( P = 0.002 ) . These results did not seem to be influenced by the type of primary renal disease . Proteinuria decreased at the end of the study by a mean of 57 % in the fosinopril group and increased by 7 % in the group receiving dihydropiridine . Blood pressure control did not differ among groups for diastolic values . During follow-up , however , the patients receiving ACEi showed systolic blood pressure values 4–6 mmHg lower . Conclusion In patients with chronic renal failure and hypertension due to primary renal disease , fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function . The drugs also differed by their capacity to lower blood pressure . The better control , in particular of systolic blood pressure , in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed Our study compared the effects of an angiotensin-converting enzyme inhibitor ( captopril ) versus a calcium antagonist ( nifedipine ) on proteinuria and renal function in patients with diabetic nephropathy . A r and omized follow-up study was design ed . Type 2 diabetic patients , with established diabetic nephropathy ( proteinuria greater than 0.5 g/24 h ) , were treated with nifedipine ( 10 patients , group A ) or captopril ( 10 patients , group B ) for 6 months . Arterial blood pressure , metabolic parameters , proteinuria and renal function were measured and compared . Mean percentage differences for glomerular filtration rate , renal plasma flow and filtration fraction between the two groups were calculated . No significant differences were observed in serum glucose , glycosylated hemoglobin ( hemoglobin A1c ) , Na+ , K+ or albumin in either group or between groups . Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months ( Mann-Whitney U-test , P = 0.03 ) . Proteinuria was similar in both groups at r and omization , but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril ( P less than 0.01 ) . A significant decrease in filtration fraction was observed in group B with an increase in group A ( Mann-Whitney U-test , P = 0.03 ) . Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria . It is concluded that antihypertensive treatment with captopril , but not with nifedipine , reduced proteinuria in patients with diabetic nephropathy , although a better mean blood pressure was obtained with nifedipine . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES The goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease ( ASCVD ) outcomes in the Atherosclerosis Risk in Communities ( ARIC ) study , a prospect i ve cohort study of subjects aged 45 to 64 years . BACKGROUND The level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD , but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community . METHODS Cox proportional-hazards regression was used to evaluate the association of glomerular filtration rate ( GFR ) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects . We search ed for nonlinear relationships between GFR and ASCVD . RESULTS During a mean follow-up time of 6.2 years , 965 ( 6.3 % ) of subjects had ASCVD events . Subjects with GFR of 15 to 59 ml/min/1.73 m(2 ) ( n = 444 , hazard ratio 1.38 [ 1.02 , 1.87 ] ) and 60 to 89 ml/min/1.73 m(2 ) ( n = 7,665 , hazard ratio 1.16 [ 1.00 , 1.34 ] ) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m(2 ) . Each 10 ml/min/1.73 m(2 ) lower GFR was associated with an adjusted hazard ratio of 1.05 ( 1.02 , 1.09 ) , 1.07 ( 1.01 , 1.12 ) , and 1.06 ( 0.99 , 1.13 ) for ASCVD , de novo ASCVD , and recurrent ASCVD , respectively . A nonlinear model did not fit the data better than a linear model . CONCLUSIONS The level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study Angiotensin converting enzyme inhibitors and calcium antagonists are effective agents for controlling high blood pressure in diabetic patients . We selected 30 type II diabetic patients with proteinuria and evaluated the effect of these drugs on renal function and proteinuria . In a double-blind trial , patients received either 40 mg/day enalapril or 40 mg/day nifedipine during 12 months . They also received a hypoproteic diet with 0.8 g/kg wt/day of protein . In the enalapril group ( 10 men and eight women ) , mean arterial blood pressure was 112.0 + /- 12 mm Hg , creatinine clearance was 58.6 + /- 12.4 ml/min , and 24-hour proteinuria was 4.36 + /- 3.23 g/24 hr before treatment . After treatment , mean arterial blood pressure was 82.0 + /- 8.30 mm Hg ( p less than 0.001 ) , creatinine clearance was 66.6 + /- 13.8 ml/min ( NS ) , and 24-hour proteinuria was 0.56 + /- 0.78 g/24 hr ( p less than 0.001 ) . In the nifedipine group ( six men and six women ) , mean arterial blood pressure was 114.0 + /- 8.0 mm Hg , creatinine clearance was 67.8 + /- 19.6 ml/min , and 24-hour proteinuria was 2.84 + /- 1.31 g/24 hr before treatment . After treatment , mean arterial blood pressure was 86.0 + /- 7.0 mm Hg ( p less than 0.001 ) , creatinine clearance was 51.4 + /- 7.9 ml/min ( p less than 0.001 ) , and 24-hour proteinuria was 2.66 + /- 0.89 g/24 hr ( NS ) . These results show a similar hypotensive action and different renal effects between these two drugs after 12 months of treatment The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria . In a r and omized , double-blind trial , 15 type 1 diabetic patients were treated with either nifedipine ( n=8 ; dosage 30 mg/day ) or placebo ( n=7 ) for 12 months . At baseline and after 6 and 12 months of therapy , the albumin excretion rate ( UAER , radioimmunoassay ) , glomerular filtration rate ( GFR , chromium 51 ethylenediamine tetra-acetic acid clearance ) and renal plasma flow ( RPF , iodine 125 hippuran clearance ) were determined . Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months ( median , Q1/Q3 in mg/24 h ) : baseline 84 ( 65/163 ) ; 6 months 35 (23/90),P<0.02 ; 12 months 39 (15/79),P<0.05 . GFR was significantly decreased by nifedipine treatment ( baseline 157±15 , 6 months 122±8 , 12 months 111±47 ml/min;P<0.05 , mean ± SEM ) , whereas RPF remained constant . Nifedipine treatment did not influence systolic ( baseline 121±7 , 12 months 124±2 mmHg , mean ± SEM ) or diastolic ( baseline 72±2 , 12 months 74±3 mmHg ) arterial blood pressure . With placebo treatment no significant alterations of UAER , GFR , RPF and arterial blood pressure were observed . Metabolic control was constant throughout the whole study period . Thus , 1 year 's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure . The data , however , do not present a recommendation for the general use of nifedipine in these patients as the exact intrarenal mechanism of calcium channel blockers in humans remains to be established OBJECTIVES We investigated the effect of achieved continuous tight blood pressure control and intensified insulin therapy on the rate of progression of renal failure in patients with overt diabetic nephropathy and already impaired renal function . DESIGN AND SETTING Prospect i ve , r and omized , multicentre , follow-up study . PATIENTS AND INTERVENTIONS From a screened group of the 66 hypertensive type 1 diabetic patients ( IDDM ) with overt diabetic nephropathy and reduced glomerular filtration rate who participated in two intensified treatment programmes , 39 patients fulfilled the study inclusion criteria and were enrolled into the 2-year follow-up period . The choice of antihypertensive drugs was based on a r and omized allocation to open antihypertensive treatments starting with felodipine , metoprolol , or ramipril . OUTCOME MEASURES Progression of renal failure was assessed by measurement of glomerular filtration rate ( GFR ) on insulin clearance every 6 months . MAIN RESULTS During the study period mean HbA1c was 8.1 + /- 1.6 % and the office blood pressure 143 + /- 14/88 + /- 8 mmHg . The change in GFRinulin ( mean and 95 % CI ) was + 1.9 ( -2.2 ; + 6.1 ) ml/min/year . GFR improved in 51 % , deteriorated in 39 % , and remained stable in 10 % of the patients . CONCLUSION This study shows that stabilization of glomerular filtration rate , as assessed by inulin clearance , is possible in patients with overt diabetic nephropathy who reach the goals of intensified antihypertensive treatment even if kidney function is already impaired BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or placebo . The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes BACKGROUND The renoprotective effect of ACE inhibition in chronic renal disease is well established but the studies on effects of calcium antagonists on progression of renal disease and on proteinuria have given varying results . METHODS We conducted an open long-term r and omized prospect i ve multi-centre study comparing the combination of ramipril and felodipine ER ( F ) with either drug alone in non-diabetic renal disease . Included were patients with uncontrolled hypertension ( diastolic blood pressure ( DBP ) ) > or = 95 mmHg on treatment with a diuretic and a beta-blocker . Fifty-one patients received the combination of R and F , 54 patients R , and 53 patients F. The treatment goal was a DBP < 90 mmHg and a similar BP reduction in the three groups . Mean doses at the last visit were 5 + 5 , 10 and 9 mg , respectively , after a mean treatment time of nearly 2 years . The progression of renal impairment was studied by serial measurements of serum creatinine , iohexol clearance , and albuminuria . RESULTS The reduction in supine systolic ( S ) BP and DBP expressed as median values were -19.0/-14.5,-14.3/-15.0 and -13.5/-13.3 mmHg in the R+F , R , and F groups , respectively . There was no significant difference between the groups . When correction for the acute drug effect was performed the R+F group had a slower progression rate of the renal disease ( loss of glomerular filtration rate ( GFR ) ml/min/year ) compared with the F group ( P<0.05 ) but not to the R group ( P>0.20 ) . There was a rise in albuminuria after 2 years in the F group ( P<0.05 ) , but no significant change was found in the other groups . CONCLUSIONS In patients with non-diabetic renal disease the combination of an ACE inhibitor and a calcium antagonist in reduced doses used in addition to baseline therapy with beta-blockers and diuretics , tended to cause a better BP reduction as each drug per se . The R+F treatment also caused a slower progression of the renal disease compared with F alone . The combination treatment seems to afford better BP control and appears to be a favourable therapeutic option in patients with renal disease and hypertension BACKGROUND Given the same level of arterial pressure control , studies in diabetic animal models have demonstrated certain classes of antihypertensive medication to confer better overall preservation of renal histologic features and function as well as reduced albuminuria when compared with other agents . The present study was design ed to assess whether any differences exist among antihypertensive agents with regard to progression of diabetic renal disease and albuminuria in human subjects . METHODS The study was a r and omized , prospect i ve , parallel group design that evaluated the effects of a converting enzyme inhibitor ( lisinopril ; group 1 ) , a calcium antagonist ( diltiazem hydrochloride ; group 2 ) , and a combination of a loop diuretic and a beta-blocker ( furosemide and atenolol ; group 3 ) in 30 subjects . All subjects received a low-salt , low-protein diet . Metabolic ( blood glucose , cholesterol profiles , and urine urea nitrogen and sodium levels ) as well as renal hemodynamic ( renal blood flow and glomerular filtration rate ) profiles and arterial pressure measurements were performed at various intervals during an 18-month period . RESULTS Both groups 1 and 2 had significantly slower rates of decline in glomerular filtration rate compared with group 3 . No significant differences were observed in renal hemodynamics between groups 1 and 2 at 18 months . Group 3 had the worst metabolic , lipid , and side-effect profile of any group . Reductions in albuminuria were not different between groups 1 and 2 , but both were significantly reduced compared with group 3 . CONCLUSIONS Given a similar level of arterial pressure control , both lisinopril and diltiazem slow progression of diabetic renal disease and reduce albuminuria to a greater extent than does the combination of a loop diuretic and beta-adrenoreceptor antagonist . These drugs were also better tolerated and produced no adverse metabolic effects Calcium antagonists exert several characteristic effects on the kidney that potentiate their antihypertensive effect . The objective of the present study was to investigate the effectiveness of nitrendipine in the presence of different degrees of renal impairment . Two groups of hypertensive patients were included in the study . Group 1:10 patients with arterial hypertension secondary to chronic renal parenchymatous disease and adequately controlled with a diuretic and /or a beta-blocker who were switched to nitrendipine . These patients were then followed monthly for 1 year . Group 2:24 patients diagnosed as having essential hypertension who presented values of urinary albumin excretion above 30 mg/day after a minimum of 3 years of adequate blood pressure control with a diuretic and /or a beta-blocker . Patients were r and omly assigned to continue with the same therapy or to switch to nitrendipine for 1 year . In both groups nitrendipine was as efficacious as st and ard therapy for controlling blood pressure and did not induce changes in renal hemodynamics . Nitrendipine did not modify the level of proteinuria in group 1 , nor the urinary excretion of albumin in group 2 . These results seem to indicate that nitrendipine can be safely used in patients with arterial hypertension and different degrees of renal function impairment OBJECTIVE The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve r and omized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications . The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy , retinopathy , and neuropathy . RESEARCH DESIGN AND METHODS The 470 hypertensive subjects , defined as having a baseline diastolic blood pressure of > or = 90 mmHg , were r and omized to intensive blood pressure control ( diastolic blood pressure goal of 75 mmHg ) versus moderate blood pressure control ( diastolic blood pressure goal of 80 - 89 mmHg ) . RESULTS The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group . During the 5-year follow-up period , no difference was observed between intensive versus moderate blood pressure control and those r and omized to nisoldipine versus enalapril with regard to the change in creatinine clearance . After the first year of antihypertensive treatment , creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria . In contrast , patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5 - 6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy . There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria ( 25 % intensive therapy vs. 18 % moderate therapy , P = 0.20 ) or microalbuminuria to overt albuminuria ( 16 % intensive therapy vs. 23 % moderate therapy , P = 0.28 ) . Intensive therapy demonstrated a lower overall incidence of deaths , 5.5 vs. 10.7 % , P = 0.037 . Over a 5-year follow-up period , there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy . In addition , the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy . CONCLUSIONS Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period . The more intensive blood pressure control decreased all-cause mortality Unlike angiotensin converting enzyme inhibitors ( ACEI ) , few long-term studies have shown calcium antagonists to retard the progression of renal dysfunction . Our aim was to prospect ively compare the effects of amlodipine and ACEI ( enalapril ) on renal function in hypertensive patients with renal impairment due to chronic glomerulonephritis and essential hypertension . A total of 72 hypertensive patients with serum creatinine ( Cr ) > 1.5 mg/dL were r and omly allocated to treatment with either drug . During a 1-year period , 33 % of the patients treated with ACEI dropped out due to adverse events , whereas 9 % of patients with amlodipine dropped out . Data of 28 patients were available for analysis of more than 1-year follow-up . Reductions in blood pressure were comparable between the amlodipine ( from 165/101 to 138/81 mm Hg ) and ACEI groups . Serum Cr increased from 2.1+/-0.8 ( SD ) to 2.6+/-1.0 mg/dL with amlodipine ( n = 16 ) , but the difference was equivalent to that with ACEI ( n = 12 ) . Creatinine clearance ( Ccr ) in the moderate dysfunction group ( basal Cr , 1.5 to 2.0 mg/dL ) changed from 36+/-10 to 33+/-11 mL/min ( not significant ) with amlodipine , and the change was similar to that noted with ACEI . Annual declines in Ccr with amlodipine ( -3.7 mL/min/year ) and ACEI ( -2.6 mL/min/year ) were comparable , and both tended to be smaller than the annual decline in glomerular filtration rate reported in the Modification of Diet in Renal Disease study ( -6 mL/min/year ) . Serum potassium was increased significantly ( P < .01 ) , from 4.5+/-0.4 to 5.3+/-0.8 mEq/L , only in the ACEI group . This 1-year prospect i ve study demonstrated the effect of amlodipine on renal function to be likely the same as that of ACEI . Furthermore , amlodipine was better tolerated than ACEI for hypertensive patients with renal dysfunction OBJECTIVE To examine the relations among proteinuria , prescribed and achieved blood pressure , and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study . DESIGN 2 r and omized trials in patients with chronic renal diseases of diverse cause . SETTING 15 outpatient nephrology practice s at university hospitals . PATIENTS 840 patients , of whom 585 were in study A ( glomerular filtration rate , 25 to 55 mliters/min.1.73 m2 ) and 255 were in study B ( glomerular filtration rate , 13 to 24 mliters/min.1.73 m2 ) . Diabetic patients who required insulin were excluded . INTERVENTIONS Patients were r and omly assigned to a usual blood pressure goal ( target mean arterial pressure , < or = 107 mm Hg for patients < or = 60 years of age and < or = 113 mm Hg for patients > or = 61 years of age ) or a low blood pressure goal ( target mean arterial pressure , < or = 92 mm Hg for patients < or = 60 years of age and < or = 98 mm Hg for patients > or = 61 years of age ) . MAIN OUTCOME MEASURES Rate of decline in glomerular filtration rate and change in proteinuria during follow-up . RESULTS The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A ( P = 0.02 ) and study B ( P = 0.01 ) . Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A ( r = -0.20 ; P < 0.001 ) and study B ( r = -0.34 ; P < 0.001 ) , and these correlations were stronger in persons with higher baseline proteinuria ( P < 0.001 in study A ; P < 0.01 in study B ) . In study A , the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear ( P = 0.011 ) and was stronger at higher mean arterial pressure . In both studies , the low blood pressure goal significantly reduced proteinuria during the first 4 months after r and omization . This , in turn , correlated with a slower subsequent decline in glomerular filtration rate . CONCLUSIONS Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease . For patients with proteinuria of more than 1 g/d , we suggest a target blood pressure of less than 92 mm Hg ( 125/75 mm Hg ) . For patients with proteinuria of 0.25 to 1.0 g/d , a target mean arterial pressure of less than 98 mm Hg ( about 130/80 mm Hg ) may be advisable . The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of this therapy in slowing the progression of renal disease BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors reduce urine protein excretion and slow the progression of renal disease . The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment . We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients . METHODS Data were analyzed from 1860 patients enrolled in 11 r and omized controlled trials comparing the effect of antihypertensive regimens , including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease . Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up . The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease . RESULTS Mean ( median ) baseline urine protein excretion was 1.8 ( 0.94 ) g/day . Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures ( interaction P < 0.001 for all ) . A higher level of urine protein excretion during follow-up ( baseline minus change ) was associated with a greater risk of progression [ relative risk 5.56 ( 3.87 to 7.98 ) for each 1.0 g/day higher protein excretion ] . After controlling for the current level of urine protein excretion , the beneficial effect of ACE inhibitors remained significant [ relative risk for ACE inhibitors vs. control was 0.66 ( 0.52 to 0.83 ) ] , but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion . CONCLUSIONS The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion . The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients . The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease . ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P<0.001 ) . Treatment with ramipril reduced the rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P<0.001 ) , myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P<0.001 ) , stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P<0.001 ) , death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P<0.001 ) , cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P<0.001 ) , and complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure AIMS Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function . Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment , but it is not known how an ACE inhibitor compares to treatment with a calcium channel blocker or to treatment with a combination of these drugs . The aim of the study was to evaluate the rate of decline in GFR in patients with chronic renal failure and hypertension treated with isradipine and spirapril as monotherapy and in combination . METHODS Sixty patients with chronic renal failure and hypertension were enrolled in the study . After enrollment , patients were followed prospect ively for 6 months in the outpatient clinic on their usual antihypertensive medication , and then r and omized to a double-blinded comparison of either spirapril 6 mg daily , isradipine 5 mg daily or spirapril 3 mg and isradipine 2.5 mg daily . After r and omization , patients were followed for 21 months or until the need for dialysis . Every 3 months before and 3.5 months after r and omization the glomerular filtration rate was measured by 51Cr-EDTA clearance and the effective renal plasma flow evaluated using the renal clearance of paraaminohippuric acid . RESULTS Blood pressure and the decline in glomerular filtration rate did not differ between the groups before r and omization . After r and omization , the mean decline in the glomerular filtration rate was -0.32 ml/(min x month x 1.73 m2 ) in the spirapril group , -0.58 ml/(min x month x 1.73 m2 ) in the isradipine group and -0.14 ml/(min x month x 1.73 m2 ) in the combination group ( p = 0.38 ) . Twelve patients , 4 in each group , reached end-stage renal failure . No significant difference was found with respect to diastolic ( p = 0.10 ) or systolic blood pressure ( p = 0.08 ) during the treatment period , but a trend towards a better blood pressure control in the combination group was present . During treatment , the rate of decline in renal plasma flow did not differ significantly between the groups ( p = 0.09 ) , neither did the changes in filtration fraction ( FF ) ( p = 0.58 ) nor the mean FF ( p = 0.22 ) during the treatment . CONCLUSIONS Our study indicated differences between the 3 treatment modalities in favor of combined therapy with respect to both the rate of decline in GFR and blood pressure control , but the differences where insignificant . Thus , the treatments might differ , but we were unable to confirm this because of large variation in GFR and small sample size The relation between proteinuria and mortality was investigated in 1188 patients with Type 1 diabetes and 3234 patients with Type 2 diabetes , aged 35 - 55 at baseline and followed up for a mean of 9.4 + /- 3.1 years in the WHO Multinational Study of Vascular Disease in Diabetes . Baseline prevalence of light or heavy proteinuria was the same ( 25 % ) in both types of diabetes after adjustment for differences in diabetes duration . Compared with patients with no proteinuria , all cause mortality ratios were 1.5 ( 95 % confidence interval 1.1 - 2.0 ) and 2.9 ( 2.2 - 3.8 ) for Type 1 patients with light and heavy proteinuria , respectively , and 1.5 ( 1.2 - 1.8 ) and 2.8 ( 2.3 - 3.4 ) for Type 2 patients , after adjustment for age , duration of diabetes , blood pressure , cholesterol , and smoking . Proteinuria was associated with significantly increased mortality from renal failure , cardiovascular disease , and all other causes of death . In both types of diabetes , the association was strongest for renal deaths , and of similar magnitude for cardiovascular and all other causes of death . In conclusion , proteinuria is a common , important , and rather non-specific risk factor for increased morbidity and mortality in diabetes . The relation of proteinuria to mortality is similar for both types of diabetes . The benefits and risks of proteinuria reduction should be examined in large r and omized trials with clinical endpoints We previously reported the renal hemodynamic effects of different antihypertensive regimens in uninephrectomized , alloxan-induced , diabetic ( DM ) beagle dogs following one year of treatment . Dogs were prospect ively r and omized to one of five groups ( N = 26 ) : nondiabetic controls , Group I ; dogs with DM on no antihypertensive drugs , Group II ; dogs on a converting enzyme inhibitor , lisinopril ( L ) , Group III ; dogs on a calcium antagonist , TA3090 ( diltiazem-like ) , Group IV ; and dogs on a combination of each drug , in reduced doses , Group V. The current paper extends our previous studies by describing the morphologic changes that occurred within each group of dogs studied . More than 100 glomeruli from the renal cortex of each dog were evaluated for increases in mesangial volume fraction ( Vv ) , glomerulosclerosis ( GS ) and ateriolar hyalinosis . The interstitium was also evaluated for associated changes . Increases in Vv were attenuated in all treated groups ( 0.28 + /- 0.04 , DM alone versus 0.16 + /- 0.05 L ; 0.21 + /- 0.07 , TA-3090 ; 0.19 + /- 0.06 micron 2/micron 2 , L+TA 3090 ; P < 0.05 ) compared to untreated DM . An attenuated increase in Vv also correlated with a blunted rise in proteinuria in Groups III ( r = 0.79 ) and V ( r = 0.81 ) but not Group IV ( r = 0.29 ) . Development of focal GS was blunted in all treated groups ; however , global GS was fourfold greater in Group IV compared to untreated DM . The degree of interstitial fibrosis also correlated with the degree of global GS . These data support the concept that both a converting enzyme inhibitor and heart rate lowering calcium antagonist attenuate morphologic progression of diabetic renal disease . ( ABSTRACT TRUNCATED AT 250 WORDS This study was undertaken to test the hypothesis that , given equal arterial pressure reductions , the combination of an angiotensin converting enzyme ( ACE ) inhibitor and calcium antagonist slows declines in renal function and yields greater reductions in albuminuria over either agent alone . This hypothesis was evaluated in four groups of hypertensive , non-insulin dependent , diabetic subjects with renal insufficiency ( N = 30 ) . Renal hemodynamics , albuminuria and metabolic parameters were evaluated for a period of one year . Subjects were all placed on a 90 mEq sodium , 0.8 g/kg protein , 1500 calorie American Diabetes Association diet for the entire length of the study . Subjects were followed for two weeks off antihypertensive medications and were subsequently r and omized to either lisinopril , alone ( group I ) , sustained release verapamil , alone ( group II ) , reduced doses of both lisinopril and sustained release verapamil ( group III ) , and hydrochlorothiazide with guanfacine ( group IV ) . At the end of one year group III had the greatest reduction in albuminuria ( 78 + /- 7 % , group III vs. 59 % + /- 4 , group I : P less than 0.05 ) . In addition , the decline in glomerular filtration rate ( GFR ) was the lowest in this group ( 0.28 + /- 0.07 , group III vs. 0.69 + /- 0.12 , group I ; P less than 0.05 ) although there was no significant difference between groups II and IV . The highest side effect profiles were noted in group IV , the least in group III . The greatest reductions in renal hemodynamics occurred in all groups within the first month ; however , striking differences between groups were noted ( 7.4 + /- 2 % , group I vs. 1.4 + /- 2 % , group III ; P less than 0.05 ) . We conclude that the combination of reduced doses of an ACE inhibitor and calcium antagonist attenuate both albuminuria and the rate of decline in glomerular filtration rate . Furthermore , the combination of these classes of agents appear to yield the lowest side effect profile over either agent alone . Lastly , high doses of ACE inhibition alone may be detrimental to renal function in late stage diabetics with renal insufficiency BACKGROUND Microalbuminuria and hypertension are risk factors for diabetic nephropathy . Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes , but similar data are lacking for hypertensive patients with type 2 diabetes . We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria . METHODS A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational , r and omized , double-blind , placebo-controlled study of irbesartan , at a dose of either 150 mg daily or 300 mg daily , and were followed for two years . The primary outcome was the time to the onset of diabetic nephropathy , defined by persistent albuminuria in overnight specimens , with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level . RESULTS The base-line characteristics in the three groups were similar . Ten of the 194 patients in the 300-mg group ( 5.2 percent ) and 19 of the 195 patients in the 150-mg group ( 9.7 percent ) reached the primary end point , as compared with 30 of the 201 patients in the placebo group ( 14.9 percent ) ( hazard ratios , 0.30 [ 95 percent confidence interval , 0.14 to 0.61 ; P < 0.001 ] and 0.61 [ 95 percent confidence interval , 0.34 to 1.08 ; P=0.081 for the two irbesartan groups , respectively ) . The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group , 143/83 mm Hg in the 150-mg group , and 141/83 mm Hg in the 300-mg group ( P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups ) . Serious adverse events were less frequent among the patients treated with irbesartan ( P=0.02 ) . CONCLUSIONS Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria BACKGROUND AND PURPOSE Increased urinary albumin and protein excretion is associated with cardiovascular disease mortality independent of other cardiovascular risk factors in subjects with non-insulin-dependent diabetes mellitus ( NIDDM ) . We assessed the relationship between the different degrees of proteinuria at baseline and the incidence of stroke , as well as other atherosclerotic vascular disease events , in a prospect i ve study of nondiabetic and NIDDM subjects . METHODS Our study was based on the 7-year follow-up of cohorts of nondiabetic ( n = 1375 ) and NIDDM ( n = 1056 ) subjects in Finl and . The urinary protein concentration at baseline was stratified into three categories : no proteinuria ( < 150 mg/L ) , borderline ( 150 to 300 mg/L ) , and clinical proteinuria ( > 300 mg/L ) . RESULTS The association between the different degrees of proteinuria and the atherosclerotic vascular events was similar in nondiabetic and NIDDM subjects . Cardiovascular disease mortality was higher both in nondiabetic and NIDDM subjects with clinical proteinuria than in those without proteinuria . The incidence of stroke was 1.6 % in nondiabetic subjects without proteinuria , 3.2 % in subjects with borderline proteinuria , and 8.5 % in subjects with clinical proteinuria ( P < .001 for trend ) . In NIDDM patients , the corresponding rates were 7.2 % , 11.1 % , and 23.0 % , respectively ( P < .001 for trend ) . The association between clinical proteinuria and the incidence of stroke remained significant both in nondiabetic and in NIDDM subjects after adjustment for other cardiovascular risk factors . Clinical proteinuria was also associated with the incidence of coronary heart disease events and that of lower-extremity amputation . NIDDM independently increased the risk of atherosclerotic vascular disease events regardless of the proteinuria status . CONCLUSIONS Clinical proteinuria significantly predicted stroke and other atherosclerotic vascular disease events independent of other cardiovascular risk factors . This finding is compatible with the view that increased urinary protein excretion rate may be associated with widespread vascular damage Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria . Calcium channel blockers ( CCBs ) have variable effects on proteinuria ; their long-term effects on progression of diabetic nephropathy are not known . The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus ( NIDDM ) by a degree comparable to ACE inhibitors , given similar levels of blood pressure control . To test this hypothesis we r and omized 52 patients with NIDDM associated nephropathy and hypertension , mean age of 63 + /- 8 years , to either the ACE inhibitor , lisinopril ( N = 18 ) , nondihydropyridine CCBs ( NDCCBs ) , verapamil SR ( N = 8) or diltiazem SR ( N = 10 ) , or the beta blocker , atenolol ( N = 16 ) . Goal blood pressure was < or = 140/90 mm Hg . Patients were followed for a mean period of 63 + /- 7 months . The primary end point was change in creatinine clearance ( CCr ) slope in each group . There was no significant difference in mean arterial pressure reduction among the groups over the study period ( P = 0.14 ) . The mean rate of decline in CCr was greatest in the atenolol group ( -3.48 ml/min/year/1.73 m2 ; P < 0.0001 ) . There was no difference in the CCr slopes between lisinopril and NDCCBs groups ( P = 0.36 ) . Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups ( P > 0.99 ) . Therefore , in persons with renal insufficiency secondary to NIDDM , similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol . Moreover , this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria , findings not observed in the atenolol group Background Angiotensin converting enzyme inhibitors have uniformly been shown to prevent the development both of proteinuria and of glomerulosclerosis in rats with a remnant kidney . Conversely , dihydropyridine calcium antagonists ( DCA ) have failed to demonstrate such a benefit in spite of causing an equivalent reduction in blood pressure . Objective To test the hypothesis that concomitant administration of an angiotensin converting enzyme inhibitor and a DCA would lead to a smaller increase both in proteinuria and in glomerulosclerosis relative to that caused by administration of a DCA alone at similar levels of blood pressure . Methods Experiments were carried out using Sprague – Dawley rats that had been subjected to five-sixths renal ablation . Animals were allocated r and omly to one of four groups : control ( no treatment ) , amlodipine ( A rats ) , benazepril ( B rats ) , or a combination of benazepril and amlodipine ( B + A rats ) . We implanted intraperitoneal sensors for telemetric monitoring of the animal 's blood pressure . Other parameters measured at baseline included proteinuria and inulin clearance . After approximately 7 weeks all of the parameters were remeasured and animals killed for morphologic assessment of the kidney . Results The B + A rats had lower levels of proteinuria than did the rats in group A ( 21 ± 12 mg/day for B + A rats versus 59 ± 24 mg/day for A rats , P < 0.05 ) . The degree of glomerulosclerosis in the B + A rats was also reduced markedly compared with that in A rats ( 12 ± 4 % for B + A rats versus 43 ± 12 % for A rats , P < 0.05 ) . Moreover , the results on proteinuria and glomerulosclerosis of B + A rats were similar to those for B rats . These differences could not be explained totally in terms of differences in blood pressure control ( 144 ± 12 mmHg in A rats versus 132 ± 13 mmHg in B + A rats , NS ) . Conclusion The results were consistent with the observation that a combination of benzepril and amlodipine provides additional protection against renal injury compared with that provided by amlodipine alone . The mechanism for this benefit is not known BACKGROUND The degree of proteinuria in patients with diabetes correlates strongly with both an increase in progression of nephropathy as well as cardiovascular events . Moreover , post hoc analyses of recent clinical trials support the concept that reductions of blood pressure and proteinuria correlate with a slowed progression of nephropathy . Both angiotensin converting enzyme ( ACE ) inhibitors and the nondihydropyridine calcium antagonists , ( non-DHPCAs ) reduce both arterial pressure and proteinuria in those with diabetic nephropathy . METHODS The present r and omized , open label , parallel group design ed study tests the hypothesis that , at similar levels of blood pressure , the combination of an ACE inhibitor , tr and olapril ( T ) with the non-DHPCA , verapamil ( V ) produces a greater reduction in proteinuria over either agent alone at one year . Thirty-seven participants , mean age 59.6 + /- 5.8 years , with nephropathy ( baseline creatinine 1.4 + /- 0.3 mg/dl and proteinuria of 1342 + /- 284 mg/dl ) secondary to type 2 diabetes completed the study . Doses of drug were titrated in each group over eight weeks to achieve a goal blood pressure of < 140/90 mm Hg . All participants were counseled to ingest a sodium diet of < 120 mEq/day . RESULTS Proteinuria reduction from baseline was significantly greater in the T+V group compared to either T alone ( -33 + /- 8 % , T vs. -62 + /- 10 % , T+V ; P < 0.001 ) or V alone ( -27 + /- 8 % , V vs. -62 + /- 10 % , T+V ; P < 0.001 ) . No significant differences in either glomerular filtration rate , arterial pressure , fasting blood glucose or urinary sodium excretion were noted at one year . The mean daily dose of the individual components of T+V ( 2.9 + /- 0.8 mg , T/219 + /- 21.1 mg V ) was significantly lower than the dose of either T alone 5.5 + /- 1.1 mg/day ( P < 0.01 ) or V alone 314.8 + /- 46.3 mg , given in two divided doses ( P < 0.01 ) . CONCLUSION These data support the concept that the combination of an ACE inhibitor with a non-DHPCA reduce proteinuria to a greater extent than either agent alone . This added antiproteinuric effect occurs at lower doses of each drug and is independent of further reductions in arterial pressure . These findings could have ramifications for slowing renal disease progression in patients with nephropathy from type 2 diabetes The present study was design ated to assess the effects of two different dyhydropyridine calcium antagonists ( DHPCAs ) on proteinuria in patients with noninsulin-dependent diabetes mellitus ( NIDDM ) . The hypothesis that similar levels of blood pressure reduction with two different DHPCAs produce similar degrees of proteinuria reduction was tested . In a prospect i ve r and omized study , 14 patients with NIDDM , hypertension , proteinuria , and renal insufficiency were given either isradipine ( n = 7 ) or nifedipine XL ( n = 7 ) for 6 months . After a 2-week washout period , patients were crossed over to the other drug and observed for an additional 6 months . Drugs were titrated to lower arterial pressure to < 140/90 mmHg . Patients also instructed to follow a low-sodium diet at the initial visit . Blood pressure and 24-hour urine values for creatinine clearance , albuminuria , proteinuria , and sodium were assessed monthly . At the end of the initial and crossover treatment periods , there were no significant reductions in the level of albuminuria from baseline with either drug . Sodium excretion was < 110 mEq/L with each drug tested . The results of this study support the concept that DHPCAs do not reduce proteinuria in patients with type II diabetes . This failure to reduce albuminuria and proteinuria occurred despite adequate blood pressure reduction and an effort at dietary sodium restriction Objective Guidelines recommend lower threshold and goal blood pressure ( BP ) for patients with proteinuria . BP reduction could be accompanied by a different fall in proteinuria depending of the antihypertensive drug . The objective was to compare proteinuria reduction when BP is lowered to the same level with different drugs . Design Prospect i ve , r and omized , double-blind , controlled trial . Setting 12 Spanish centres . Patients A total of 119 patients with primary renal disease , blood pressure > 130/85 mmHg , proteinuria > 1 g/day , and creatinine clearance ⩾ 50 ml/min . Intervention After a 4-week run-in placebo period , patients were r and omized to : atenolol 50 mg/day ; tr and olapril 2 mg/day ; verapamil 240 mg/day or verapamil 180 + tr and olapril 2 mg/day combination ; forced double-dose titration was carried out at the 4th week . Treatment duration was 6 months . Outcome measures Changes in BP , 24 h proteinuria , serum albumin and calcium . Results BP was significantly reduced with the four treatments [ SBP/DBP ( mmHg ] : atenolol 12.2/9.9 ; tr and olapril 12.9/9.3 ; verapamil 8.2/7.9 and verapamil + tr and olapril 13.6/11.3 ) without differences between them . A significant fall in proteinuria was seen in the tr and olapril , 40.2 % [ 95 % confidence interval ( CI ) 24.3–56.2 % ] , and verapamil + tr and olapril groups , 48.5 % ( 95 % CI , 31.7–64.3 % ) accompanied with increases in serum albumin ( tr and olapril : from 3.86 ± 0.64 to 4.03 ± 0.67 g/dl ; verapamil + tr and olapril : from 4.15 ± 0.58 to 4.40 ± 0.51 g/dl ) . Conclusions In patients with proteinuric primary renal disease , adequate dose titration of antihypertensive drugs may provide a substantial BP reduction . Only angiotensin-converting enzyme inhibitor ( tr and olapril ) treatment , alone or better combined with verapamil , reduces proteinuria and increases serum albumin Contrasting information has been reported concerning the course of renal function in NIDDM with hypertension alone or in association with renal damage . The aim of the present study was to eluci date the course of the glomerular filtration rate ( GFR ) in hypertensive NIDDM patients during antihypertensive therapy . Furthermore , we compared the effects of ACE inhibitors ( cilazapril , Inibace , Roche , Milan , Italy ) and Ca2 + -channel blockers ( amlodipine , Norvasc , Pfizer , Rome , Italy ) . Of the hypertensive NIDDM patients attending the outpatient 's clinic of the internal medicine departments of the University of Padova and Sassari , 44 participated in the present study . Of these patients , 26 were normoalbuminuric and 18 microalbuminuric . They were r and omly treated with either cilazapril or amlodipine . The target of antihypertensive treatment was a value < 140 mmHg for systolic and 85 mmHg for diastolic blood pressure ( BP ) . Microalbuminuria was defined as an albumin excretion rate ( AER ) between 20 and 200 μg/min . GFR was measured by plasma clearance of 51Cr-labeled EDTA at baseline and every 6–12 months during a 3-year follow-up interval . A significant decrease was observed in the values of GFR , AER , and systolic and diastolic BP in normoalbuminuric and microalbuminuric patients during antihypertensive therapy . The GFR fall in the overall population of NIDDM patients was significantly and inversely related to the decrease of mean BP ( diastolic + 1/3 pulse pressure ) ( r = −0.80 , P < 0.0001 ) but not to that of HbA1c , triglycerides , and BMI . The GFR decline ( mean ± SE ) per year in the normoalbuminuric patient was 2.03 ± 0.66 ml · min−1 · 1.73 m−2 ( 95 % CI 0.92–3.17 ) during cilazapril and 2.01 ± 0.71 ml · min−1 · 1.73 m−2 ( 95 % CI 0.82–3.11 ) during amlodipine therapy . The GFR decline per year in the microalbuminuric patient was 2.15 ± 0.69 ml · min−1 · 1.73 m−2 ( 95 % CI 0.86–3.89 ) during cilazapril and 2.33 ± 0.83 ml · min−1 · 1.73 m−2 per year ( 95 % CI 1.03–3.67 ) during amlodipine therapy . Cilazapril and amlodipine lowered AER to a similar extent in normoalbuminuric and microalbuminuric patients . No significant changes were observed concerning other clinical and biochemical features between the two antihypertensive therapies and particularly HbA1c , BMI , triglycerides , and cholesterol plasma values . These results support the tenet that arterial hypertension plays a pivotal role in contributing to renal damage in NIDDM , even when AER is normal . However , the degree of BP control , with both cilazapril and amlodipine , can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy Microalbuminuria in patients with essential hypertension is associated with increased incidence of cardiovascular morbidity and mortality . Reduction of urinary albumin excretion ( UAE ) with therapy could reduce cardiovascular events . The long-term effect of commonly used antihypertensive agents on UAE has not been properly investigated . In the present study , we have prospect ively studied the effects of therapy for 24 months with a converting enzyme inhibitor , enalapril , or a calcium channel blocker , nicardipine , on UAE in 40 patients with essential hypertension and microalbuminuria . Enalapril and nicardipine were equally effective in reducing arterial pressure . However , enalapril decreased UAE from 77.1 + /- 10.4 to 30.4 + /- 7.9 mg/24 h after 1 year , and to 24.7 + /- 4.8 ( P < .01 ) after 2 years of therapy . UAE however , did not change in patients treated with nicardipine ( from 65.2 + /- 12 to 73 + /- 14 after 1 year , and to 52.7 + /- 21 mg/24 h after 2 years of therapy ) . The impact of reducing UAE on overall cardiovascular morbidity and mortality and on future progression of renal failure in patients with essential hypertension remains to be established BACKGROUND Calcium channel blockers ( CCBs ) are known to have differential effects on both changes in proteinuria as well as progression of diabetic nephropathy . No clinical study , however , has evaluated whether the differential antiproteinuric effects of CCBs may be explained by their effect on glomerular membrane permeability . We , therefore , tested the hypothesis that certain subclasses of CCBs reduce proteinuria by changing size selectivity of the glomerular membrane , hence changing its permeability . METHODS Twenty-one patients with type 2 diabetes and the presence of nephropathy with hypertension were r and omized to receive either diltiazem CD or nifedipine GITS after baseline data for mean systolic and diastolic pressure , urinary protein excretion , glomerular filtration rate , renal plasma flow , neutral dextran and IgG clearances were obtained . Glomerular filtration rate , renal plasma flow , neutral dextran and IgG clearance were measured every three months , arterial pressure and heart rate every month . Patients were followed for 21 months . RESULTS At 21 months , both patient groups had similar levels of blood pressure control , however , only the diltiazem group had a change in proteinuria ( 4+/-10%delta , nifedipine vs. -57+/-18%delta , diltiazem ; P < 0.001 ) with improvement in glomerular size selectivity and change in IgG clearance . CONCLUSIONS These data support the hypothesis that CCBs that provide sustained reductions in proteinuria do so , in part , by improving glomerular size permselectivity The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined . We screened 1635 men with a history of hypertension and r and omized 1292 with untreated diastolic blood pressure ( DBP ) 95 - 109 mmHg to single-drug treatment with either hydrochlorothiazide , atenolol , captopril , clonidine , diltiazem-SR , prazosin , or placebo in a double-blind prospect i ve trial . Twenty-seven of 1635 patients ( 1.7 % ) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study . Follow-up data were obtained on 19 of these 27 patients . One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease . Three other patients developed severe ( serum creatinine > 3.5 mg/dl ) chronic renal failure ( one with diabetic nephropathy ) , one progressed from serum creatinine 1.4 to 2.2 mg/dl , but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6 - 9 years . Data were available for 1076 of 1155 ( 93 % ) treated study patients at end titration , 522/600 ( 87 % ) at one year and 322/444 ( 73 % ) at two years . There were significant associations for proteinuria with obesity and higher systolic blood pressure . There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black ( 127 mg ) and white ( 139 mg ) patients ( p = 0.07 ) . There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups ( including placebo ) . Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours : hydrochlorothiazide 4 , placebo 3 , diltiazem 3 , prazosin 3 , atenolol 2 , clonidine 2 , and captopril 1 . We conclude : ( 1 ) the prevalence of severe ( > 1 g/24 hours ) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis ; ( 2 ) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs ; and ( 3 ) there was no drug-specific increase in proteinuria detected in this study BACKGROUND Restricting protein intake and controlling hypertension delay the progression of renal disease in animals . We tested these interventions in 840 patients with various chronic renal diseases . METHODS In study 1 , 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were r and omly assigned to a usual-protein diet or a low-protein diet ( 1.3 or 0.58 g of protein per kilogram of body weight per day ) and to a usual- or a low-blood-pressure group ( mean arterial pressure , 107 or 92 mm Hg ) . In study 2 , 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were r and omly assigned to the low-protein diet ( 0.58 g per kilogram per day ) or a very-low-protein diet ( 0.28 g per kilogram per day ) with a keto acid-amino acid supplement , and a usual- or a low-blood-pressure group ( same values as those in study 1 ) . An 18-to-45-month follow-up was planned , with monthly evaluations of the patients . RESULTS The mean follow-up was 2.2 years . In study 1 , the projected mean decline in the glomerular filtration rate at three years did not differ significantly between the diet groups or between the blood-pressure groups . As compared with the usual-protein group and the usual-blood-pressure group , the low-protein group and the low-blood-pressure group had a more rapid decline in the glomerular filtration rate during the first four months after r and omization and a slower decline thereafter . In study 2 , the very-low-protein group had a marginally slower decline in the glomerular filtration rate than did the low-protein group ( P = 0.07 ) . There was no delay in the time to the occurrence of end-stage renal disease or death . In both studies , patients in the low-blood-pressure group who had more pronounced proteinuria at base line had a significantly slower rate of decline in the glomerular filtration rate . CONCLUSIONS Among patients with moderate renal insufficiency , the slower decline in renal function that started four months after the introduction of a low-protein diet suggests a small benefit of this dietary intervention . Among patients with more severe renal insufficiency , a very-low-protein diet , as compared with a low-protein diet , did not significantly slow the progression of renal disease BACKGROUND Clinical trials of nephropathy in people with type 2 diabetes mellitus have not examined the effects of systolic blood pressure ( SBP ) or pulse pressure ( PP ) on the time to end-stage renal disease ( ESRD ) or death . OBJECTIVES To evaluate the impact of baseline and treated SBP , diastolic blood pressure ( DBP ) , and PP on composite and individual outcomes including doubling of serum creatinine , ESRD , or death in participants of the Reduction of Endpoints in NIDDM ( non-insulin-dependent diabetes mellitus ) With the Angiotensin II Antagonist Losartan ( RENAAL ) Study ; to assess the specific effect of the angiotensin receptor blocker losartan potassium on composite and renal outcomes ; and to explore the implication s of dihydropyridine calcium channel blockers as concurrent therapy on composite and renal outcomes . DESIGN A Cox proportional hazards regression model was used to assess the hazard risk profile of baseline SBP ( categories : < 130 , 130 - 139 , 140 - 159 , 160 - 179 , and > or = 180 mm Hg ) , DBP ( categories : < 70 , 70 - 79 , 80 - 89 , 90 - 99 , and > or = 100 mm Hg ) , and PP ( categories : < 60 , 60 - 69 , 70 - 79 , 80 - 89 , and > or = 90 mm Hg ) on renal outcomes . PARTICIPANTS The study comprised 1513 participants with established nephropathy and hypertension associated with type 2 diabetes . INTERVENTIONS The RENAAL study was a r and omized , placebo-controlled study of losartan vs placebo , with other agents added to achieve the goal of a trough BP ( ie , BP immediately prior to the next dosing ) below 140/90 mm Hg , and had a mean follow-up of 3.4 years . MAIN OUTCOME MEASURES The primary analysis was time to composite end point of doubling of serum creatinine , ESRD , or death . RESULTS A baseline SBP range of 140 to 159 mm Hg increased risk for ESRD or death by 38 % ( P = .05 ) compared with those below 130 mm Hg . In a multivariate model , every 10-mm Hg rise in baseline SBP increased the risk for ESRD or death by 6.7 % ( P = .007 ) ; the same rise in DBP decreased the risk by 10.9 % ( P = .01 ) when adjusting for urinary albumin-creatinine ratio , serum creatinine , serum albumin , hemoglobin , and hemoglobin A1c . Those r and omized to the losartan group with a baseline PP above 90 mm Hg had a 53.5 % risk reduction for ESRD alone ( P = .003 ) and a 35.5 % risk reduction for ESRD or death ( P = .02 ) compared with the placebo group . CONCLUSIONS Baseline SBP is a stronger predictor than DBP of renal outcomes in those with nephropathy result ing from type 2 diabetes . Those with the highest baseline PP have the highest risk for nephropathy progression but also garner the greatest risk reduction with SBP lowered to less than 140 mm Hg The purpose of this study was to compare the effects of ramipril and nitrendipine on urinary albumin excretion ( UAE ) in hypertensive patients with non-insulin-dependent diabetes mellitus ( NIDDM ) and impaired renal function . Forty patients with mild hypertension with NIDDM and persistent albuminuria ( > 300 mg/24h ) were studied . After a 3-week run-in period on placebo , patients were r and omly treated with ramipril 5 mg once daily or nitrendipine 20 mg once daily for 6 months , according to a double-blind design . Blood pressure ( BP ) , UAE , creatinine clearance and glycosilated haemoglobin were evaluated at the end of the placebo period and after 1,3 and 6 months of active treatment . Both ramipril and nitrendipine significantly lowered BP values without affecting glucose homeostasis and renal function . Despite equivalent BP control , only ramipril afforded a significant reduction in UAE , thus suggesting that the antiproteinuric effect of ramipril is at least partially independent of its anti-hypertensive effect The long-term effects of converting enzyme inhibitors and calcium channel blockers on proteinuria and the progression of renal disease in patients with hypertension and chronic renal insufficiency are not well established . We have studied the long-term effects of treating hypertension with an angiotensin-converting enzyme inhibitor , enalapril , and a calcium channel blocker , nicardipine , on urinary albumin excretion ( UAE ) and on renal function in 16 patients with hypertension and chronic renal insufficiency ( creatinine clearance ranging between 17 and 62 ml/min ) . After 1 year of treatment , these agents caused a similar decrease in blood pressure . Only enalapril , however , caused a significant decrease in UAE ( from 641 + /- 98 to 292 + /- 47 mg/24 h , p less than 0.01 ) , whereas UAE did not change in the group treated with nicardipine ( 675 + /- 78 vs. 601 + /- 75 mg/24 h ) . Creatinine clearance at the beginning of the study was similar in the group treated with enalapril and in the group treated with nicardipine ( 35 + /- 3.6 vs. 40 + /- 4.1 ml/min ) . After 1 year of follow-up , creatinine clearance remained unchanged in both groups of patients . These studies demonstrate that both enalapril and nicardipine can effectively reduce blood pressure in patients with hypertension and chronic renal insufficiency . Enalapril but not nicardipine , however , appears to reduce urinary albumin excretion in these patients . Whether the reduction in UAE has any significant impact on the progression of renal disease remains to be established |
2,107 | 29,605,330 | There was no multivariable model developed to assess variables associated with calving to pregnancy interval but , univariably , increased metabolizable energy balance was associated with a shorter calving to pregnancy interval whereas increased milk production was associated with longer time to pregnancy .
Increased intake of some AA , particularly threonine and lysine , were associated with a longer calving to pregnancy interval .
It is clear nutritional management around calving can influence reproductive success .
The importance of dietary fats and increased energy and protein balances in early lactation for improved fertility outcomes is supported and suggests that starch and sugars may have different effects on the proportion of cows that are pregnant to AI . | This meta- analysis of 39 experiments containing 118 treatments explored the effects of diet interventions in early lactation on the proportion of dairy cows pregnant to artificial insemination ( AI ; pregnancy to AI ) and on calving to pregnancy interval .
It also identified factors that may explain variation in these responses .
The objectives were to identify effects of diet on reproduction , rather than differences between specific dietary interventions . | One hundred and twenty early lactating Holstein dairy cows were assigned to investigate the effect of dietary chromium ( Cr ) supplementation ( 0 or 6 mg Cr/head/day from organic preparation ) on the productive and reproductive performance as well as on some blood serum parameters under heat stress ( 35 - 40 degrees C ) . Cows received treatment from 3 weeks pre-partum through 12 weeks post-partum . Chromium supplemented diet had lower body weight loss and improved dry matter intake with consequent reduction in the energy balance deficits during the first period after calving when compared with the control group . Chromium supplementation increased ( p < 0.05 ) milk yield by 6.7 % , 12.3 % and 16.5 % at 4 , 8 and 12 weeks post-partum , respectively , whereas milk composition and milk to feed ratio were unaffected ( p > 0.05 ) when compared with the control . Moreover , dietary Cr supplementation had no effect ( p > 0.05 ) on blood serum glucose , calcium and phosphorus concentrations . A reduction ( p < 0.05 ) of non-esterified fatty acids at 1 week pre-partum , 2 and 4 weeks post-partum was also observed . Serum insulin concentration increased whereas cortisol concentration decreased , when compared with the control group , throughout the whole experimental period . Also Cr supplementation showed a trend towards improving reproductive performance as indicated by increased percentage of pregnant cows in the first 28 days of breeding . It could be concluded that dietary Cr supplementation at level of 6 mg/head/day may offer a potential protective management practice to lessen the effect of heat stress in dairy cattle OBJECTIVE To evaluate the effects of length of exposure to prepartum transition diets on milk yield , fat and protein production . DESIGN Prospect i ve cohort study . The number of days that the cows were fed the prepartum transition diets was the exposure of interest . PROCEDURES Holstein and Holstein x Jersey cows ( n = 1008 ) were enrolled . Diets given in the far-off dry period ( from end of lactation until approximately 3 weeks before expected parturition ) consisted of ad libitum access to perennial ryegrass pastures . Prepartum transition diets included perennial ryegrass pasture , ryegrass silage , cereal hay , grain , grain by-product , protein meals , BioChlor , sodium monensin , virginiamycin or tylosin , MgSO(4 ) , trace elements and vitamins . On a dry matter basis , these contained 16.0 % crude protein , 4.2 % rumen undegradable protein , and 9.9 mJ metabolisable energy/kg . Diets provided an estimated metabolisable protein balance of 286 g/day and dietary cation anion difference of -150 meq/kg dry matter . Statistical models controlled for effects of herd , calving day , breed , age and gestation period . RESULTS Increasing length of exposure to the prepartum transition diets significantly increased the 4.0 % fat- and 3.2 % protein-corrected milk yield and milk-protein yield as a linear and quadratic effect . The optimal duration of exposure to the prepartum transition diets was 25 days for fat- and protein-corrected milk production and 22 days for milk protein production . Milk-fat percentage decreased significantly and linearly with increasing exposure to the prepartum transition diets ; however , milk-fat yield or milk-protein percentage did not vary significantly with duration of exposure to the diets . CONCLUSIONS Increasing exposure to prepartum transition diets increased milk and milk-protein yields and decreased the milk fat-percentage , but not the milk-protein percentage or milk-fat yield Milk protein concentration in dairy cows has been positively associated with a range of measures of reproductive performance . It was possible that these associations were due to confounding by milk volume . A retrospective single cohort study was conducted using data collected from 74 dairy herds with seasonal or split calving patterns . Associations between milk protein concentration and reproductive performance in Holstein dairy cows were assessed using r and om effects logistic regression . The key finding from this study was that the associations between milk protein concentration in early lactation and reproductive performance were not due to confounding by milk yield . Associations between milk protein concentration and reproductive performance were weaker at higher early lactation milk yields , but positive associations were evident at all milk volumes assessed . The second major finding was that increases in milk yield were associated with improved proportions of cows pregnant by wk 6 and 21 at low to moderate milk protein concentrations but with decreases in these reproductive measures at high milk protein concentrations . Thus , no simple relationship is present between milk yield and reproductive performance ; effects of milk yield depend on milk protein concentration . These results indicate that mechanisms causing the associations between milk protein concentration and reproductive performance may be linked to milk yield but these mechanisms operate over a wide range of milk yields ( < 2,000 to ≥5,000 kg in the first 120d of lactation ) . Further research is required to identify the causes of these associations Twenty preparturient dairy cows were in a 2-yr switchover design to test effects of dietary ions on incidence of milk fever . In yr 1 , cows were blocked and assigned r and omly 45 days prepartum to one of two diets ; one diet contained an excess of anions , and the second diet contained an excess of cations . In yr 2 , cows were changed to the opposite diet . Both diets were equivalent for crude protein ( 11 % ) , calcium ( .65 % ) , phosphorus ( .25 % ) , and energy on a dry basis but differed for quantities of chlorine , sulfur , and sodium . Both diets were chopped alfalfa hay , corn silage , high moisture corn , and vitamin-mineral mix . Diets were available ad libitum as complete rations . There were no differences in dry matter intake of the diets . Cows consuming the anionic diet had no milk fever , but cows consuming the canionic diet had 47.4 % incidence . Sample s of blood plasma showed that cows consuming the anionic diet maintained calcium and phosphorus through parturition , whereas cows consuming the cationic diet decreased in these minerals around calving . Hydroxyproline was higher for cows consuming the anionic diet during the peripartal period compared to cows consuming the cationic diet . Milk produced in the lactation subsequent to prepartum treatment was 6.8 % less for cows offered the cationic diet . When milk production of paretic and nonparetic cows offered the cationic diet was compared , milk was reduced 14 % with milk fever Forty-six multiparous Holstein cows were assigned at 5 d postpartum to a completely r and omized design employing a 2 x 3 factorial arrangement of treatments . Factors were 0 and 5 % added prilled long-chain fatty acids ( DM basis ) and three forage to concentrate ratios ( 45:55 , 64:36 , 84:16 ) . Diets consisted of immature alfalfa silage and a concentrate of shelled corn and soybean meal with or without fat replacing a portion of the corn . Mean plasma concentration of cholesterol was higher for cows fed 5 % vs. 0 % fat and increased over the first 100 d in milk for all animals regardless of treatment . There were no differences in reproductive performance due to either of the main effects . Mean plasma progesterone was higher due to fat treatment in the mid to late luteal phase of the second postpartum cycle as well as the metestrous to early luteal phase and mid to late luteal phase of the third cycle . Even though progesterone concentrations were higher in cows fed 5 % fat during the luteal phase after breeding , the conception rates at this service were not different from those fed 0 % fat . The biological significance of increased plasma progesterone concentration was not identified with any postpartum reproductive trait measured in this trial Conjugated linoleic acid ( CLA ) reduces mammary milk fat synthesis in a dose-dependent manner . Our objective was to determine the effects of lipid-encapsulated CLA ( LE-CLA ) supplementation on milk production , reproductive performance and metabolic responses in lactating dairy cows fed a grass silage-based diet . Seventy-two Holstein-Friesian cows ( 32 primiparous and 40 multiparous ) were used in a completely r and omized block design . Cows received either 80 g of LE-CLA daily or 60 g of calcium salts of palm fatty acids daily ( control ) from parturition until 60 days in milk . LE-CLA contained a 50:50 mix of cis-9,trans-11 CLA and trans-10,cis-12 CLA , result ing in a daily intake of 6 g of each isomer . Milk production and dry matter intake were recorded daily , and blood sample s were collected 3-times a week . Blood sample s were analysed for circulating concentrations of glucose , non-esterified fatty acids ( NEFA ) , β-hydroxybutyrate ( BHBA ) , insulin and insulin-like growth factor-I ( IGF-I ) . Progesterone was measured in blood sample s collected after the first post-partum insemination . Ovarian ultrasound examinations commenced at 8 - 10 d post partum and were carried out 3-times a week until first ovulation . LE-CLA treatment result ed in decreased milk fat concentration , with consequent improvements in energy balance and body condition score ( BCS ) . The peak concentration of NEFA in blood was reduced by LE-CLA , but circulating concentrations of insulin , glucose , IGF-I , BHBA and progesterone were not affected . There was no effect of LE-CLA supplementation on the post-partum interval to first ovulation . Services per conception tended to be reduced . The reduction in milk energy output and improvement in energy status and BCS in LE-CLA-supplemented cows provides a strong rationale for further studies with greater cow numbers to test effects on reproductive performance Clinical mastitis and reproductive records from two southern California dairy herds were used in a cross-sectional study to determine the risk of an altered interestrus interval following clinical mastitis . An altered interestrus interval was defined as cycles occurring at either less than 18 day or more than 24-day intervals . The data were stratified by herd to assess herd differences and by lactation number to assess confounding by cow parity . The predominant pathogen isolated from mastitis cases in Herd 1 was Staphylococcus aureus , whereas the predominant pathogens in Herd 2 were gram-negative isolates . Cows in Herd 1 which had coliforms cultured from mastitic milk were excluded in the analysis for comparison with Herd 2 . In Herd 1 , cows with clinical mastitis were less likely to have an altered interestrus interval ( Relative Risk [RR]=0.9 ; 95 % Confidence Interval [CI]=0.6,1.6 ) than herdmates without clinical mastitis . However , cows in Herd 2 were almost two times more likely to have an altered interestrus interval following an episode of clinical mastitis compared to herdmates without clinical mastitis ( RR=1.6 ; 95 % CI=1.3,2.0 ) . Because herd management practice s differ and could cause differences in mastitis and reproductive outcomes at the dairies , this preliminary field evidence should be followed by prospect i ve studies of luteal function after clinical coliform mastitis The effects of grain , fructose , and histidine on ruminal pH and fermentation products were studied in dairy cattle during an induced subacute acidosis protocol . Thirty Holstein heifers were r and omly allocated to 5 treatment groups : ( 1 ) control ( no grain ) ; ( 2 ) grain [ fed at a crushed triticale dry matter intake ( DMI ) of 1.2 % of body weight ( BW ) ] ; ( 3 ) grain ( 0.8 % of BW DMI)+fructose ( 0.4 % of BW DMI ) ; ( 4 ) grain ( 1.2 % of BW DMI)+histidine ( 6 g/head ) ; and ( 5 ) grain ( 0.8 % of BW DMI)+fructose ( 0.4 % of BW DMI)+histidine ( 6 g/head ) in a partial factorial arrangement . Heifers were fed 1 kg of grain daily with ad libitum access to ryegrass silage and alfalfa hay for 10 d. Feed was withheld for 14 h before challenge day , on which heifers were fed 200 g of alfalfa hay and then the treatment diets immediately thereafter . Rumen sample s were collected 5 min after diet ingestion , 60 min later , and at 3 subsequent 50-min intervals . Grain decreased ruminal pH and increased ammonia , total volatile fatty acid ( VFA ) , acetate , butyrate , propionate , and valerate concentrations compared with controls . The addition of grain had no effect on ruminal D- and L-lactate concentrations . Fructose markedly decreased ruminal pH and markedly increased D- and L-lactate concentrations . Fructose increased total VFA and butyrate and decreased valerate concentrations . Although histidine did not have a marked effect on ruminal fermentation , increased concentrations of histamine were observed following feeding . This study demonstrates that the substitution of some grain for fructose can lower ruminal pH and increase VFA and lactate concentrations , warranting further investigation into the role of sugars on the risk of acidosis in dairy cattle The aim of this study was to investigate the relationship between measures of body condition score collected from calving until wk 26 of lactation and reproductive measures ( calving interval , days to first heat , days to first service , and conception at first service ) . Since 1973 sires of cows at the Langhill Dairy Cattle Research Centre have been selected for either high ( selection line ) or average ( control line ) genetic merit for fat plus protein . The data included 1211 records from 534 cows calving from 1988 to 1999 . At first calving , cows were r and omly assigned to one of two ad libitum diets : one that was relatively high in concentrates ( approximately 3000 kg/yr ) and one that was relatively low in concentrates ( approximately 1500 kg/yr ) . Selection line cows were on average thinner and lost more condition in early lactation than control line cows . Cows that lost condition , those that were thinner than average at wk 10 of lactation and those that were thinner on average over the first 10 wk , had poorer reproductive performance . This effect was greatest in the selection line . Line x diet interaction effects were not statistically significant . Genetic correlations between body condition score and reproductive measures were unfavorable and ranged from -0.04 to -0.54 . The relationship between body condition score and production was strong , but , even after adjusting for yield , an unfavorable relationship still exists between body condition score and fertility . Body condition score could be used as a management and selection tool to improve reproductive performance The objective of this study was to determine the effects of feed restriction and source of dietary fatty acids during the close-up dry period on postcalving reproductive performance of dairy cattle . Thirty-four days before expected calving , pregnant Holstein cows ( n = 72 ; parity 1 to 5 ) were r and omly assigned to 1 of 6 treatments . Treatments were ad libitum ( AL ) or 24 % feed restriction ( FR ) in combination with 1 of 3 oilseed supplements at 8 % of diet dry matter : canola , linola , or flax to enrich the rations with oleic , linoleic , or linolenic fatty acids , respectively . After calving , cows were fed a common lactation diet that contained no oilseeds . Measurements of uterus , corpus luteum , and follicles were obtained by ultrasonography twice weekly from 7 + /- 1 d after calving until the first ovulation . Cows ( n = 66 ) were subjected to timed artificial insemination ( TAI ) , and pregnancy was determined 32 d later . Feed-restricted cows had lower dry matter intake and lost more body weight prepartum . Energy balance ( Mcal/d ) was negative in FR cows prepartum but they had a less severe negative energy balance postpartum . The dietary source of fatty acid did not affect energy balance . Cows fed AL had a higher incidence of uterine infections ( 10/37 vs. 2/35 ) but tended to have fewer ovarian cysts ( 2/37 vs. 7/35 ) than FR cows . Mean ( + /-SE ) interval from calving to uterine involution did not differ among dietary treatments ( 26.8 + /- 1.8 d ) . Interval from calving to first ovulation was longer in cows fed canola than in those fed either linola or flax ( 34.7 + /- 3.1 vs. 23.7 + /- 3.2 and 21.0 + /- 3.1 d , respectively ) . A greater percentage of cows fed AL conceived to the first TAI ( 47.1 vs. 18.8 ) and tended to have fewer mean days open ( 157 + /- 10.8 vs. 191 + /- 10.1 ) than cows fed FR . In summary , FR cows had a lower incidence of uterine infections , but they were less fertile as reflected by a lower percent pregnancy to first TAI and increased days open . Cows fed diets enriched in linoleic or linolenic fatty acids had a lesser incidence of ovarian cysts and ovulated sooner with no effect on energy balance or fertility Primiparous ( n = 22 ) and multiparous ( n = 41 ) cows were r and omly assigned by calving date and parity to one of four dietary sequences of supplemental fat from 14 d prepartum to 151 d postpartum . Partially hydrogenated tallow was added to diets at 0 % prepartum and postpartum ( control ) ; 1 % prepartum and 2 % postpartum ; 0 % prepartum and 2 % postpartum ; and 0 % prepartum , 0 % from 1 to 34 d postpartum , and 2 % from 35 to 151 d postpartum . Inclusion of partially hydrogenated tallow did not influence yields of milk or 3.5 % FCM , milk composition , or DMI during the first 151 d postpartum . During the first 35 d postpartum , cows receiving partially hydrogenated tallow starting at parturition yielded milk with a higher fat content than those receiving fat prepartum and postpartum . Addition of partially hydrogenated tallow to diets starting 35 d postpartum result ed in cows being more persistent in yields of milk and 3.5 % FCM from 60 to 151 d postpartum . Reproduction parameters measured were unaffected by time of fat addition to diets . Our data suggest that delaying the addition of partially hydrogenated tallow to diets until 35 d postpartum may improve the persistency of lactation Twenty primigravid Holsteins were paired by expected calving date and estimated producing ability and assigned r and omly to one of two diets to determine the effect of prepartum supplemented undegradable protein on subsequent productive performance . Diets were isocaloric , isonitrogenous for degradable protein and differed in undegradable protein content . Prepartum diets were fed for ad libitum intake for 3 wk prior to calving . Following parturition , a single diet was offered for ad libitum intake . Cows did not differ in initial BW or body condition score . Body condition score , BW , and milk composition were measured weekly , starting at calving through the first 6 wk of lactation , Milk production was measured daily . Prepartum diet did not influence calf birth weight or mean prepartum DMI . Prepartum diet containing increased undegradable protein improved body condition score at calving through wk 6 postcalving and increased milk protein percentage . Mean daily protein production was consistently greater for the prepartum diet with additional undegradable protein . Milk , FCM , and milk fat were not influenced by prepartum diet . Supplemental undegradable protein prepartum may improve postpartum performance by minimizing mobilization of maternal labile protein pools to meet fetal and maternal growth requirements in late gestation Adding 0 , 5 , 15 , and 20 % of substrate as prilled or unprilled fatty acids [ palmitic ( 47 to 48 % ) , stearic ( 36 to 37 % ) , and oleic ( 14 % ) acids ] to an in vitro rumen fermenter had no effect on total VFA production . Acetate : propionate ratio was reduced by fatty acid concentrations of 15 and 20 % ( prilled and unprilled ) . In a 4 x 4 Latin square , increasing dietary prilled fatty acids ( 0 , 3 , 6 , or 9 % of DM ) decreased DM intake , increased percentage of milk fat , and had no effect on percentage of milk protein . Milk volume and FCM increased with 3 % but decreased with 6 and 9 % dietary fatty acids . Rumen fluid acetate : propionate decreased with increasing dietary fatty acids . Holstein cows in three herds in Pennsylvania and Friesian cows in an Israeli herd were assigned r and omly to receive , from 0 to 110 to 150 d postcalving , diets containing 0 or 2 % of DM prilled fat . In Israel , dietary fat increased milk yield , FCM , and fat percentage during the first 90 d postcalving . In Pennsylvania , prilled fat had variable effects on milk composition and little effect on milk yield and FCM . Conception rate was improved in cows consuming rations containing prilled fat : first service , 59.1 versus 42.6 % ; all services , 59.3 versus 40.7 % . The inclusion of prilled fat at 2 % of DM in dairy cattle rations had slight effects on rumen fermentation , variable effects on milk yield and composition , and beneficial effects on conception rate The influence of high protein diets ( 21 % CP , DM basis ) , containing varied percentages of RUP , on lactation performance and fertility was evaluated . Sixty-two Holstein cows ( 65 % multiparous ) were blocked by age and r and omly assigned to a 2 x 2 x 2 factorial design from d 12 to 125 postpartum . Factor 1 was 0 or 3.5 % fish meal diet , factor 2 was location ( Calan door versus free stall ) , and factor 3 was parity ( first versus second or later ) . The soybean meal diet consisted of alfalfa hay , corn silage , barley , and soybean meal . The fish meal diet contained 3.5 % fish meal ( ruminant grade menhaden ) that replaced a portion of the soybean meal . Cows fed the fish meal diet ( 40 % RUP ) had DMI , BW , and body condition similar to those of cows offered the soybean meal diet ( 34 % RUP ) . Cows receiving the fish meal supplement tended to have higher milk protein production throughout the trial , higher milk production during the first 6 wk , and significantly lower ruminal ammonia concentrations than cows receiving the soybean meal diet . Differences in reproductive performance were not significant except for a diet by housing location interaction for conception rates from first AI The objectives of this study were to observe endocrine and reproductive responses of cows and heifers fed two diets ( 16 and 19 % CP ) , which met undegradable protein requirements but differed in rumen degradable protein . Cows ( n = 33 ) and heifers ( n = 32 ) were r and omly assigned within parity to diets at calving and remained on diets for 20 d after first breeding . Energy balance was determined twice weekly through the first luteal phase . Blood and milk sample s were taken three times per week . Diet did not affect average daily energy balance , days to negative energy balance nadir , days to first ovulation , days to first service , or plasma glucose concentrations . First service conception rate was lower ( 31 % vs. 48 % ) and plasma urea higher in animals fed the high protein diet . Days to energy balance nadir was correlated with days ( r = .75 ) to first ovulation . Luteinizing hormone pulse frequency increased and pulse amplitude decreased in frequent sample s ( 12-min intervals for 8 h ) collected at 14 d postpartum versus sampling after the energy balance nadir . These data suggest that energy balance status plays an important role in determining the postpartum return of cyclic ovarian activity . Feeding excess CP as rumen degradable protein elevated plasma urea concentrations and decreased first service conception rate Reproductive performance in the high-yielding dairy cow has severely decreased in the last 40 yr . The aim of this study was to compare the effectiveness of 4 nutritional strategies in improving the reproductive performance of high-yielding dairy cows . It was hypothesized that offering cows a high-starch ration in early lactation would enhance the onset of luteal activity , and that decreasing the severity of negative energy balance in the early postcalving period would improve reproductive parameters . Nutritional regimens aim ed at improving fertility were applied to 96 Holstein-Friesian dairy animals . Upon calving , animals were allocated in a balanced manner to one of 4 dietary treatments . Primiparous animals were balanced according to live weight , body condition score and calving date . Multiparous animals were balanced according to parity , previous lactation milk yield , liveweight , body condition score and calving date . Treatment 1 was based on an industry best practice diet ( control ) to contain 170 g of crude protein/kg of dry matter . Treatment 2 was an individual cow feeding strategy , whereby the energy balance ( EB ) of individual animals was managed so as to achieve a predetermined target daily EB profile ( ±10 MJ/d ) . Treatment 3 was a high-starch/high-fat combination treatment , whereby an insulinogenic ( high-starch ) diet was offered in early lactation to encourage cyclicity and followed by a lipogenic ( low-starch , high-fat ) diet to promote embryo development . Treatment 4 was a low-protein diet , containing 140 g of crude protein/kg of dry matter , supplemented with protected methionine at an inclusion level of 40 g per animal per day . The nutritional strategies implemented in this study had no statistically significant effects on cow fertility measures , which included the onset of luteal activity , conception rate , in-calf rate , and the incidence of atypical cycles . The individual cow feeding strategy improved EB in early lactation but had no benefit on conception rate to first insemination . However , conception rate to second insemination , 100-d pregnancy rate ( from the commencement of breeding ) , and overall pregnancy rate tended to be higher in this group . The high-starch/high-fat treatment tended to decrease the proportion of delayed ovulations and increase the proportion of animals cycling by d 50 postcalving . Animals that failed to conceive to first insemination had a significantly longer luteal phase in the first cycle postpartum and a longer inter-ovulatory interval in the second cycle postpartum . With regards to estrous behavior , results indicate that as the size of the sexually active group increased , the intensity of estrus and the expression of mounting or attempting to mount another cow also increased . Furthermore , cows that became pregnant displayed more intense estrous behavior than cows that failed to become pregnant The objective of this study was to determine the effect of different duration s of n-3 supplementation during the peripartal period on production and reproduction performance of Holstein dairy cows . Thirty-two Holstein dry cows ( 16 multiparous and 16 primiparous ) were blocked within parity for similar expected calving date s 8 wk before calving . Cows within blocks were assigned r and omly to 1 of 4 treatments : ( 1 ) control without n-3 fatty acid ( FA ) supplementation during the dry period ; ( 2 ) n-3 FA supplementation during the whole dry period ( 8 wk ) ; and ( 3 ) n-3 FA supplementation during the early dry period ( first 5 wk ; far-off ) , or ( 4 ) n-3 FA supplementation during the late dry period ( last 3 wk ; close-up ) . All cows received the same diet without n-3 FA after calving for the first 6 wk of lactation . Ovaries of each cow were examined 10 , 17 , 24 , and 34 d from calving ( calving = d 0 ) by transrectal ultrasonography to determine follicular development . Blood sample s were collected at 14-d intervals starting on the first day of the dry period ( 8 wk before expected calving ) to determine plasma concentrations of glucose , β-hydroxybutyrate , nonesterified fatty acids , urea N , aspartate aminotransferase , and insulin . Blood sample s were also collected on d 1 , 10 , 17 , 24 , 31 , and 38 postpartum for determination of progesterone concentration . Milk yield was recorded daily throughout the experiment and sample s were taken twice weekly ( Monday and Thursday mornings ) for analysis of fat , protein , and lactose . Yields of milk and 4 % fat-corrected milk and milk composition were similar among treatments except for fat proportion , which tended to be lower in cows that were fed n-3 FA throughout the dry period . We observed no differences among treatments for plasma concentrations of metabolites and hormones . The cows that were fed in the 3 n-3 FA treatments had larger ovulatory follicles compared with those fed the controlled diet . Treatments did not differ significantly in terms of the number of days open , day to first service , or number of services per pregnancy . In conclusion , n-3 FA supplementation throughout the dry period or in the early or late prepartal period had no carryover reproductive postpartum benefits and no effect on the production of Holstein dairy cows |
2,108 | 22,749,606 | The most frequent PSDs found in people with epilepsy were depressive symptoms , memory functions , quality of life , anxiety , stigma , locus of control , cognitive functions in general , and emotional functions in general .
It can be stated that patients ' life areas are affected by cognitive , emotional , and psychological problems . | The aims of this paper are to identify factors that influence the psychosocial difficulties ( PSDs ) that persons with epilepsy experience in their everyday life , to describe their onset and the way they evolve over time , and to analyze the determinants of changes over time and other related variables . | Objective : To determine changes in depression and anxiety after resective surgery . Methods : Data from subjects enrolled in a prospect i ve multicenter study of resective epilepsy surgery were review ed with the Beck Psychiatric Symptoms Scales ( Beck Depression Inventory [ BDI ] and Beck Anxiety Inventory [ BAI ] ) and Composite International Diagnostic Interview ( CIDI ) up to a 24-month period . χ2 analyses were used to correlate proportions . Results : A total of 358 presurgical BDI and 360 BAI results were review ed . Moderate and severe levels of depression were reported in 22.1 % of patients , and similar levels of anxiety were reported by 24.7 % . Postoperative rates of depression and anxiety declined at the 3- , 12- , and 24-month follow-up periods . At the 24-month follow-up , moderate to severe levels of depression symptoms were reported in 17.6 and 14.7 % of the patients who continued to have postoperative seizures . Moderate to severe depression and anxiety were found in 8.2 % of those who were seizure-free . There was no relationship , prior to surgery , between the presence or absence of depression and anxiety and the laterality or location of the seizure onset . There were no significant relationships between depression or anxiety at 24-month follow-up and the laterality or location of the surgery . Conclusions : Depression and anxiety in patients with refractory epilepsy significantly improve after epilepsy surgery , especially in those who are seizure-free . Neither the lateralization nor the localization of the seizure focus or surgery was associated with the risk of affective symptoms at baseline or after surgery PURPOSE Psychological interventions in the treatment of epilepsy have been developed and evaluated for many years but the amount of research has hardly made an impact on how epilepsy is treated . The purpose of this study was to develop and evaluate a psychological treatment program consisting of acceptance and commitment therapy ( ACT ) together with some behavioral seizure control technology shown to be successful in earlier research . METHODS The method consisted of a r and omized controlled trial group design with repeated measures ( n=27 ) . All participants had an EEG verified epilepsy diagnosis with drug refractory seizures . Participants were r and omized into one of two conditions , ACT or supportive therapy ( ST ) . Therapeutic effects were measured by examining changes in quality of life ( SWLS and WHOQOL ) and seizure index ( frequency x duration ) . Both treatment conditions consisted of only nine hours of professional therapy distributed in two individual and two group sessions during a four-week period . RESULTS The results showed significant effects over all of the dependent variables for the ACT group as compared to the ST group at six- and twelve-month follow-ups . CONCLUSIONS The results from this study suggest that a short-term psychotherapy program combined with anticonvulsant drugs may help to prevent the long-term disability that occurs from drug refractory seizures OBJECTIVES The goals of this study were to observe behavioral changes in patients receiving levetiracetam ( LEV ) , a newer antiepileptic drug ( AED ) , and to answer the question of whether LEV exerts a specific effect on impulse control and aggression . METHODS We asked 288 consecutive patients with epilepsy on LEV ( 90 % polytherapy , mean dose=2689 mg ) and 135 relatives whether LEV caused a positive or negative behavioral change . Forty-three patients on other AEDs served as a control group . Ratings were related to patient characteristics , efficacy , dose , drug load , bidirectional ratings of change in behavioral domains , and question naires on personality ( Fragebogens zur Persönlichkeit bei zerebralen Erkrankungen ) and impulsivity ( Barratt Impulsiveness Scale-11 ) . RESULTS LEV was rated as very effective by 40 % of the patients . In contrast to only 9 % of the controls , a considerable number of patients reported a behavioral change while taking LEV ( 12 % very negative , 25 % negative , 16 % positive , 6 % very positive ) . Negative ratings were due to loss of self-control , restlessness , sleep problems , and , most importantly , aggression . Positive ratings were due to increased energy , vigilance , and activation . Increases in psychomotor speed , concentration , and remote memory indicated subjectively experienced positive effects on cognition . The proxy reports indicated reliable self-reports . Reported change was not related to type of epilepsy , co-therapy , dose , drug load , or psychiatric history . Negative effects were , however , associated with poorer seizure control , mental retardation , indicators of an organic psychosyndrome , and nonplanning impulsiveness . CONCLUSION The results indicate that LEV exerts a dose-independent stimulating effect that can be positive or negative . Aggression is a prominent feature . Lack of efficacy , mental retardation , and presumably also pre-intake disposition ( organic psychosyndrome , impulsivity ) may be helpful in predicting whether additional activation under LEV will be positive or negative A few previous studies have revealed impairments in remote memory in patients with temporal lobe epilepsy , but many questions about the importance of lesion side , type of material , seizure history and deficits in other aspects of cognitive functions remain unanswered . In this study , patients who had undergone unilateral ( 15 right and 15 left ) temporal lobectomy ( TL ) for the relief of epilepsy and 15 control subjects completed a range of public and autobiographical memory tests . Deficits in recall and recognition of details related to past famous world events were observed for both left and right TL groups . In addition , the left TL group showed impaired retrieval of famous names and TL patients as a group generated significantly fewer names of people from their own past . Current seizure- and medication-status influenced performance on a few measures , but duration of epilepsy and age of onset had no significant impact . Underlying cognitive deficits ( especially naming ability ) contributed to , but could not completely explain difficulties remembering the past . In particular , deficits in the ability to retrieve highly specific information learned in the past , such as names of famous people or details about famous events , remained evident in analyses that controlled for the impact of related cognitive skills Considerable interest has been focused on the psychiatric complications of medically refractory temporal lobe epilepsy ( TLE ) before and after epilepsy surgery . The aim of the present study was to evaluate the psychiatric status , quality of life , and level of disability in medically refractory mesial temporal lobe epilepsy ( MTLE ) patients , a homogenous subgroup of patients with TLE , before and after anterior temporal lobectomy ( ATL ) . The study population consisted of 22 patients with medically refractory MTLE who were c and i date s for ATL . Patients were examined before surgery as well as in the third and sixth months of the postoperative period . Psychiatric diagnosis was determined by using SCID-I. To rate the severity of psychiatric disorders , BPRS , HDRS , and HARS were employed on each visit . WHO-DAS-II and WHOQOL-BREF were used to determine the level of disability and quality of life . Preoperatively , six patients had a psychiatric diagnosis . Three months after surgery , six of the patients had psychiatric diagnoses . Five of these six patients had not been previously diagnosed . There was no significant difference between preoperative and postoperative follow-up evaluations in terms of HDRS , HARS , and BPRS ratings . With respect to the total scores and domains of WHO-DAS-II , the change in pre- and postoperative evaluations was statistically significant only for the social life attendance domain . There was no significant difference in the mean scores on the WHOQOL-BREF domains or on the first question about general evaluation of quality of life . For the second question on the level of satisfaction with health , the difference between the three ratings was statistically significant . Preoperative and postoperative rates of psychiatric disorders in our sample were low . While social phobia was frequently seen preoperatively , the postoperative period was spearheaded by major depressive disorder . The decrease in disability in attendance to social life and improvement in the quality of health were in concordance with the literature , indicating the positive results of surgical treatment of epilepsy on quality of life . This study suggests that surgical intervention might be one of the causes of postoperative psychiatric disorders in patients with MTLE Objective – To explore effectiveness , tolerability and changes in quality of life in patients with epilepsy converting to topiramate ( TPM ) from carbamazepine ( CBZ ) or oxcarbazepine ( OXC ) due to insufficient effectiveness and /or tolerability Quality of life is impaired in patients with epilepsy and can be improved by effective therapy . R and omised clinical trials have shown that lamotrigine treatment is associated with improved quality of life . However , little information is available on quality of life or treatment effects in patients with epilepsy in the general population . The objective of this study was to estimate the impact of lamotrigine on quality of life in a naturalistic treatment setting . The study included adult patients with epilepsy in whom lamotrigine therapy was initiated . Each subject completed the Quality of Life in Epilepsy Inventory (QOLIE)-31 quality of life question naire at inclusion and at a follow-up visit in the next 4 months . Demographic information and medical history were provided by the investigator . These were evaluated as potential determinants of change in quality of life using logistic regression . Three hundred and forty-one patients were evaluated , 192 starting lamotrigine in combination with another drug , 90 as a first-line monotherapy , 45 as a switch from another drug and 14 as a reduction to monotherapy from a previous combination . Baseline scores on the QOLIE-31 ranged from 53.8 in the combination group to 69.5 in the first-line group . 34.6 % of patients were considered to be responders , with no significant differences between treatment regimen . Most improvement was seen for the energy-fatigue and medication effects subscales and , for the first-line group , seizure worry . Seizure type was the only determinant of improvement of quality of life identified . In conclusion , lamotrigine treatment is associated with improved quality of life , regardless of treatment regimen The aim of this prospect i ve , multicenter , open-label study was to investigate the efficacy of levetiracetam ( LEV ) and determine its effects on cognitive and neuropsychological function . Sixty-nine patients were evaluated for effects of LEV on seizure control , cognitive ( Mini-Mental State Examination [ MMSE ] ) and neuropsychological ( Symptom Checklist-90 Revised [ SCL-90-R ] ) functions , and quality of life ( Quality of Life in Epilepsy--10 [ QOLIE-10 ] ) assessment s at 3 and 12 months of follow-up . Thirty-nine percent of patients achieved seizure freedom , and 68 % had a > or = 50 % seizure frequency reduction after 1 year of LEV ( 1235.5+/-392.7 mg/day ) . There were also significant improvements in mean MMSE score and in the recall and language items of MMSE . There were modest improvements in interpersonal sensitivity and paranoid ideation scales of the SCL-90-R , and improvements in cognition and medication effect items of the QOLIE-10 . The results demonstrate that LEV not only effectively reduces seizure frequency , but also possibly contributes to improvements in neuropsychological functions such as recall , language , interpersonal sensitivity , and paranoid ideation PURPOSE To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures . METHODS This r and omized , double-blind , parallel-group study in adults with partial seizures included an 8-week escalation phase , during which adjunctive lamotrigine ( n = 132 ) or adjunctive levetiracetam ( n = 136 ) was titrated to a target dose , and a 12-week , double-blind maintenance phase , during which dosages of study medication and concomitant antiepileptic drugs were maintained . The primary endpoint was change from baseline to the end of the maintenance phase ( week 20 ) in the Anger-Hostility subscale score of the Profile of Mood States ( POMS ) . RESULTS Improvement with lamotrigine relative to levetiracetam was observed for mean + /- SD ( st and ard deviation ) change from baseline to the end of the maintenance phase ( week 20 ) on the Anger-Hostility subscale ( lamotrigine -2.0 + /- 8.2 , levetiracetam -0.3 + /- 8.4 ; p = 0.024 ) ( the primary endpoint ) ; the Anger-Hostility subscale on weeks 5 , 6 , 7 , 8 , 9 , 11 , 12 , 14 , 16 , 18 , and 19 ; and the Total Mood Disturbance score on weeks 6 , 7 , 8 , 9 , 11 , 12 , 17 , 19 , and 20 . Improvement ( p < 0.05 ) with lamotrigine relative to levetiracetam was also observed on the POMS subscales Depression-Dejection , Vigor-Activity , Fatigue-Inertia , and Confusion-Bewilderment . No difference in seizure frequency was observed between groups . The most common adverse events with both medications were headache and dizziness . DISCUSSION Adjunctive lamotrigine significantly improved Anger-Hostility subscale scores relative to adjunctive levetiracetam in patients with partial seizures at the end of 20 weeks . This difference was consistently observed throughout the treatment period . Similar improvement with lamotrigine versus levetiracetam was observed for other mood symptoms AIM The purpose of this prospect i ve clinical study was to examine the short- and long-term psychosocial outcomes of a consecutive series of patients who underwent extratemporal lobe resection due to medically-refractory epilepsy . MATERIAL S AND METHODS The sample consisted of 23 consecutive patients and all patients completed a question naire assessing especially psychosocial outcome 6 months and 2 years after surgery . Results obtained at short- and long-term follow-ups were compared to baseline . Furthermore , the impact of seizure freedom on the psychosocial outcome was sought . RESULTS The results suggested that , psychosocial outcome was improved after surgery compared to preoperative status regardless of seizure status . At long-term follow-up , significant improvements were found in social and psychological variables ( p < 0.05 ) . Levels of side effects from medication were high at long-term compared to baseline ( p = 0.003 ) . Seizure free patients showed better psychosocial outcome than those who had seizure during the postoperative period , however ; only the " impact of epilepsy " scale showed significant improvement at 6 months after surgery ( p = 0.02 ) . CONCLUSION These results provide evidence that surgery caused appreciable improvements in psychosocial well-being , however ; seizure freedom is not key to improving the psychosocial life of patients who have undergone extratemporal lobe epilepsy surgery Health‐related quality of life ( HRQOL ) improves after resective epilepsy surgery , but data are limited to short follow‐up in mostly retrospective reports , with minimal consideration of other potential factors that might influence HRQOL Background : Surgery for intractable temporal lobe epilepsy usually controls seizures and improves health-related quality of life ( HRQOL ) , but some patients experience continued seizures , memory decline , or both . The relative impact of these unfavorable outcomes on HRQOL has not been described . Methods : We studied seizure control , memory change , and HRQOL among 138 patients in the Multicenter Study of Epilepsy Surgery ( MSES ) , an ongoing , prospect i ve study of epilepsy surgery outcomes . Seizure remission at 2 years and 5 years was prospect ively determined based upon regularly scheduled follow-up calls to study patients throughout the follow-up period . HRQOL was assessed annually using the Quality of Life in Epilepsy Inventory ( QOLIE-89 ) . Memory decline was determined by change in verbal delayed recall from baseline to the 2- or 5-year follow-up . Results : HRQOL improved in patients who were in remission at the 2-year or 5-year follow-up , regardless of memory outcome . Among those not in remission at both 2 and 5 years ( 25/138 , 18 % ) , HRQOL remained stable when memory did not decline ( 14/138 , 10 % ) , but HRQOL declined when memory did decline ( 11/138 , 8 % ) . These 11 patients had baseline characteristics predictive of poor seizure or memory outcome . Declines were most apparent on HRQOL subscales assessing memory , role limitations , and limitations in work , driving , and social activities . Conclusions : After temporal resection , health-related quality of life ( HRQOL ) improves or remains stable in seizure-free patients despite memory decline , but HRQOL declines when persistent seizures are accompanied by memory decline . These results may be useful in presurgical counseling and identifying patients at risk for poor psychosocial outcome following surgery OBJECTIVE This prospect i ve , case control study evaluates quality of life ( QOL ) , depressive affect , and memory outcomes of epilepsy patients implanted with a vagus nerve stimulator ( VNS ) . METHODS Three groups of patients with epilepsy underwent assessment on two occasions : 1 ) patients with a VNS were tested before and 12 months after implantation ( n = 16 ) ; 2 ) patients who underwent cerebral resective surgery were tested pre- and post-operatively ( n = 10 ) ; and 3 ) patients under medical management ( n = 9 ) . Group means were compared on the QOLIE-89 , Geriatric Depression Scale , Wechsler Memory Scale - III , and the Memory Observation Question naire . Secondary analyses calculated the reliable change index , providing information on change beyond measurement error and chance . RESULTS Mean ratings of QOL , depression , and memory complaints and objective memory scores remained stable or improved in all the groups . The QOL improved more after cerebral resective surgery than VNS or medication controls , but the VNS and medication control groups did not differ . In the VNS group , QOL was not related to seizure reduction . The percentage of cases showing real change in memory was equivalent across groups , except in one of eight indices ( i.e. , verbal recognition memory ) . CONCLUSIONS This first case controlled design found that vagus nerve stimulation as an adjunctive therapy for seizure control did not change QOL , depressive affect , or objective memory scores over one-year more so than medical management alone . We point out the need for larger case control , non-industry funded investigations OBJECTIVE Quality of life ( QOL ) was assessed in patients who switched to oxcarbazepine monotherapy because of the lack of efficacy or poor tolerability of their current antiepileptic drug ( AED ) . METHOD This open-label , single-arm study consisted of patients aged 12 > or= years with partial onset seizures . Oxcarbazepine ( 8 - 10mg/kg/day for children , 600 mg/day for adults ) was titrated up over 4 weeks while the existing AED was tapered off . QOL was evaluated at baseline and end of study ( Week 16 ) using the vali date d-in-epilepsy QOLIE-31 question naire . RESULTS For all patients who completed the QOLIE-31 at baseline and completion , a statistically significant improvement was noted for both the composite and multi-item subscale QOL scores ( P<0.05 vs baseline ) . Statistically significant mean percentage improvements of > or=10 % from baseline ( range=10.8 - 50.1 % ) were also noted . Significant improvements were seen in health-related QOL for patients who experienced seizure freedom or > or=50 % reductions in seizure frequency with oxcarbazepine monotherapy . CONCLUSIONS Patients with partial seizures who switched to oxcarbazepine monotherapy showed statistically significant , clinical ly relevant improvements in QOL OBJECTIVE The goal of the work described here was to develop and pilot a theoretically based self-management intervention in adults with epilepsy . METHODS A r and omized , controlled trial examined intervention effectiveness of a 6-week psychosocial intervention design ed to improve self-efficacy and quality of life for 61 adults with diagnosed epilepsy . Measures included the Quality of Life in Epilepsy-89 inventory ( QOLIE-89 ) , the Washington Psychosocial Seizure Inventory ( WPSI ) , a locus of control scale ( LOC ) , and the Epilepsy Self-Efficacy Scale-2000 ( ESES ) . Group differences were examined between groups using analysis of covariance . RESULTS There was a significant improvement in the QOLIE-89 Role Limitations -Emotional score in the treatment group at follow-up , but no significant differences in overall quality of life . Strong and significant correlations were observed between outcome measures . CONCLUSION Although the intervention had little effect on improving overall quality of life , we observed promising trends in postintervention group comparisons linking self-efficacy and other psychosocial factors with quality of life . Intervention material can be modified for stage-based behavior change and retested in another study BACKGROUND Interictal depression is common in patients with epilepsy and it significantly impacts quality of life . Some studies indicate that levetiracetam ( LEV ) may have mood stabilizing properties . METHODS Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV . Patients were evaluated for depression and anxiety with several psychometric measures , including : Montgomery and Asberg Depression Rating Scale ( MADRS ) , Hamilton Depression Rating Scale ( HDRS ) , Zung Self-rating Scale for Depression ( Z-SDS ) , Hamilton Anxiety Rating Scale ( HARS ) , Zung Self-rating Scale for Anxiety ( Z-SAS ) . RESULTS Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety . CONCLUSIONS This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures . However , the sample of patients is limited and the possibility of a placebo effect can not be excluded . These findings must be considered preliminary and should be replicated under placebo-controlled conditions PURPOSE We have developed a new approach to characterizing psychosocial outcome after seizure surgery that allows us to identify diverse individual trajectories as well as subgroups of patients with similar outcomes . METHODS Eighty-nine anterior temporal lobectomy ( ATL ) patients were recruited through our Seizure Surgery Follow-up and Rehabilitation Program . The Austin CEP Interview was used to measure psychosocial adjustment presurgery , at discharge , and 1 , 3 , 6 , 12 , and 24 months postsurgery . Patient outcome trajectories were characterized across this time frame using a profile-focused form of dual clustering that leads to a lattice representation . RESULTS Two major , distinct outcome subgroups were identified . Fifty-eight percent ( 58 % ) of patients reported good outcomes , characterized by improved family dynamics , enhanced vocational and social functioning , and driving by 24 months postsurgery . A range of trajectories led to these outcomes , including the experience of early postoperative adjustment difficulties . In contrast , 31 % of patients perceived their outcomes as poor , reporting affective disturbance at 12 months and difficulties discarding sick role behaviors . Early anxiety served as a marker of poor outcomes , while resolution of early anxiety and vocational change at 12 months were indicators of good outcomes at 24 months . The remaining 11 % of patients reported minimal adjustment features . CONCLUSIONS For the majority of patients , seizure surgery gives rise to an evolving process of postoperative adjustment that leads to distinct outcome trajectories . Our approach questions the clinical sensitivity of health-related quality of life measures that average across patients to provide a unitary measure of outcome . Although preliminary , the findings have implication s for postoperative treatment , including the identification of markers of longer-term outcomes Objective : To compare the impact of policies of immediate vs deferred treatment in patients with few or infrequent seizures on quality of life ( QoL ) outcomes . Methods : We conducted a multicenter , r and omized , unblinded study of immediate and deferred treatment . QoL data were collected by mail , using vali date d measures , for participants living in the UK and without major learning disability . Baseline question naires were returned by 441 adult patients ; 333 returned 2-year follow-up question naires . This analysis is based on 331 patients ( 162 r and omized to immediate , 169 to deferred treatment ) returning both baseline and 2-year question naires . Results : There were no significant differences at 2 years in QoL outcomes by treatment group . Patients r and omized to deferred treatment were no more likely to report impairments in general health , cognitive function , psychological well-being , or social function . The one area of functioning affected was driving , where those r and omized to deferred treatment were disadvantaged . There were clear QoL impacts both of taking antiepileptic drugs and , to an even greater extent , of continuing seizures . Conclusions : In treatment uncertain patients , there is a clear trade-off between adverse effects of seizures and adverse effects of taking antiepileptic drugs , i.e. , neither policy examined in our study was associated with overall quality of life gains or losses longer term Objectives – To explore effectiveness , tolerability and quality of life in elderly patients with epilepsy treated with topiramate This study prospect ively examined whether continued add-on treatment with oxcarbazepine ( OXC ) is associated with quantitative improvement in mood and anxiety symptoms in adult patients with partial epilepsy . Depressive symptoms and anxiety were assessed by clinical interview using the Hamilton Depression Rating Scale ( HDRS ) , the Cornell Dysthymia Rating Scale ( CDRS ) , the Beck Depression Inventory ( BDI ) , and the Hamilton Anxiety Rating Scale ( HARS ) . Forty controls ( patients with epilepsy treated with antiepileptic drugs other than OXC ) and 40 OXC-treated patients were enrolled and completed the study . In our study , a significant improvement in affect , as measured by the CDRS , was demonstrated during the course of OXC treatment for 3 months . HDRS and BDI scores also declined in the OXC-treated group , but these decreases did not reach statistical significance . In addition , 28 of 40 OXC-treated subjects who were dysthymic by CDRS criteria on study entry ( score > or = 20 ) demonstrated affective improvement consistent with a treatment-related antidepressant effect ( score < 20 ) . Although our results do not provide conclusive evidence supporting the specific use of OXC as an antidepressant , the significant decline in dysthymic symptoms in OXC-treated subjects compared with controls lends support to the hypothesis that OXC improves mood Treating seizures among patients with mental retardation/developmental disabilities ( MR/DD ) is difficult owing in large part to the presence of additional comorbidities and the result ing need for polytherapy . Therefore , a nonpharmacological treatment option is needed for this population . This prospect i ve , open-label study documented the long-term outcome of 40 low-IQ ( < 70 ) patients living in long-term care facilities who received vagus nerve stimulation ( VNS ) therapy for pharmacoresistant epilepsy . Subjects were seen every 1 to 3 months by their neurologist ( R.H. ) . Seizure frequency , antiepileptic medication , and quality -of-life information were documented preimplantation and quarterly thereafter through 2 years . The surgery and therapy were well tolerated . Seizures were reduced by at least 50 % for 11 subjects . Antiepileptic medications were reduced from 3.3 per subject at baseline to an average of 2.3 per subject after 2 years . According to caregiver reports , overall quality of life improved for the majority of subjects ; also , using the Client Development Evaluation Report ( CDER ) , statistically significant improvements were reported at both 1 and 2 years in attention span , word usage , clarity of speech , st and ing balance , washing dishes , and household chores . VNS is a viable treatment option for low-IQ patients with pharmacoresistant epilepsy who are living in long-term care facilities |
2,109 | 23,835,732 | When drinkers and moderate drinkers were compared , a significantly higher incidence of surgical site infection and anastomotic leakage was found in unadjusted studies .
In the meta- analysis of studies adjusting for smoking and age , alcohol drinking did not significantly affect surgical site infection and anastomotic leakage .
The RCTs did not show any effect of perioperative alcohol abstinence or pharmacological withdrawal treatment on outcome .
Conclusions Alcohol drinking is not an independent risk factor for surgical site infection and anastomotic leakage .
Interventions which aim to make patients quit alcohol or treat withdrawal symptoms do not seem to affect the surgical outcomes of interest | Background Alcohol abuse appears to increase postoperative complications , but clinical trials have reported conflicting results .
The objective of this systematic review and meta- analysis is to clarify how alcohol drinking affects postoperative surgical site infection and anastomotic leakage and to determine the impact of perioperative alcohol intervention . | OBJECTIVE To show clinical benefit in the main outcome measures by the use of a st and ardized protocol for identification , characterization , and treatment of alcohol withdrawal syndrome ( AWS ) in postoperative patients with head and neck cancer . DESIGN Prospect i ve cohort study with a retrospective cohort control . SETTING Tertiary care university . PATIENTS A total of 26 consecutive postoperative patients with AWS were selected from among 652 patients with head and neck cancer to be enrolled in the protocol from March 2003 through March 2005 . Controls consisted of 14 of 981 consecutive patients with AWS from March 2000 through December 2002 . INTERVENTION Application of a st and ardized care protocol . MAIN OUTCOME MEASURES Sensitivity and specificity of preoperative screening for AWS risk , predictability of outcomes , length of stay , transfers to the intensive care unit ( ICU ) , AWS symptoms , postoperative morbidity and mortality , doses of pharmacotherapy required , and charges . RESULTS Protocol patients demonstrated significantly fewer AWS-related ICU transfers and less delirium and violence than pre protocol patients . Mortality , wound complications , hospital charges , and doses of benzodiazepines , clonidine , and haloperidol were not significantly different between these 2 groups . Preoperative medical history correlated poorly with AWS outcomes . Screening was 87.5 % sensitive and 99.7 % specific . Late enrollees to the protocol ( false-negative screening results ) showed many significantly worse outcomes than immediate enrollees . CONCLUSION Use of the st and ardized AWS symptom-triggered protocol decreased delirium , violence , and AWS-related ICU transfers without significantly increasing hospital charges Abstract Objective : To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day . Design : R and omised controlled trial . Setting : Copenhagen , Denmark . Subjects : 42 alcoholic patients without liver disease admitted for elective colorectal surgery . Interventions : Withdrawal from alcohol consumption for 1month before operation ( disulfiram controlled ) compared with continuous drinking . Main outcome measures : Postoperative complications requiring treatment within the first month after surgery . Perioperative immunosuppression measured by delayed type hypersensitivity ; myocardial ischaemia and arrhythmias measured by Holter tape recording ; episodes of hypoxaemia measured by pulse oximetry . Response to stress during the operation were assessed by heart rate , blood pressure , serum concentration of cortisol , and plasma concentrations of glucose , interleukin 6 , and catecholamines . Results : The intervention group developed significantly fewer postoperative complications than the continuous drinkers ( 31 % v 74 % , P=0.02 ) . Delayed type hypersensitivity responses were better in the intervention group before ( 37 mm2 v 12 mm2 , P=0.04 ) , but not after surgery ( 3 mm2 v 3 mm2 ) . Development of postoperative myocardial ischaemia ( 23 % v 85 % ) and arrhythmias ( 33 % v 86 % ) on the second postoperative day as well as nightly hypoxaemic episodes ( 4 v 18 on the second postoperative night ) occurred significantly less often in the intervention group . Surgical stress responses were lower in the intervention group ( P≤0.05 ) . Conclusions : One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers . The mechanism is probably reduced pre clinical organ dysfunction and reduction of the exaggerated response to surgical stress In a prospect i ve study of 7735 middle-aged 7 British men , 504 of whom died in a follow-up period of 7.5 years , there was a U-shaped relationship between alcohol intake and total mortality and an inverse relationship with cardiovascular mortality , even after adjustment for age , cigarette smoking , and social class . These mortality patterns were seen in all smoking categories ( with ex-smoking non-drinkers having the highest mortality ) and were observed in manual but not in non-manual workers . The alcohol-mortality relationships ( total and cardiovascular ) were present only in men with cardiovascular or cardiovascular-related doctor-diagnosed illnesses at initial examination . The data suggest that the observed alcohol-mortality relationships are produced by pre-existing disease and by the movement of men with such disease into non-drinking or occasional-drinking categories . The concept of a " protective " effect of drinking on mortality , ignoring the dynamic relationship between ill-health and drinking behaviour , is likely to be ill founded AIM To assess the effectiveness of a tailored pre-operative intervention for excessive alcohol consumption in reducing post-operative complications and alcohol consumption thereafter . METHODS Patients scheduled for elective surgery requiring at least overnight hospitalisation were screened for alcohol misuse . Consenting , eligible participants with > or = 7 days to surgery at the time of screening were offered an intervention and those with < 7 days to surgery were provided usual care . RESULTS Over a period of 2 years and 10 months , 3139 patients were screened to recruit 136 participants . Baseline analysis revealed a mean age of 53 ( + /-15.8 ) years and a mean consumption of 71 g/day ( + /-48.1 ) . The intervention group ( n = 45 ) did not differ significantly from controls ( n = 91 ) in age , consumption , and number of current smokers , but there were significantly more women in the control group . There was no difference between the groups in major or minor complications experienced , or length of stay after controlling for age , gender , and baseline consumption . At 6-month follow-up there was a significant reduction in drinking for the entire study population . CONCLUSION The study did not demonstrate any beneficial effect of the pre-operative intervention on post-operative complications . The relatively short time to surgery , intervention by a non-member of the surgical team , challenges to recruitment and reduced consumption in the control group may have limited the ability of the study to detect a significant effect of the intervention Postoperative morbidity after hysterectomy was prospect ively studied in 229 consecutive patients in our departments . The incidence of alcohol abuse ( greater than 60 gm of alcohol daily ) and social drinking ( between 25 and 60 gm of alcohol daily ) was 6.5 % for each . When compared with the social drinkers and the control group , the alcohol abuse group had significantly more complications ( 80 % vs 27 % and 80 % vs 13 % , respectively ) PURPOSE Morbidity after radical cystectomy is common and associated with increased health care re source use . Accurate characterization of complications after cystectomy , associated patient specific risk factors , and perioperative processes of care are essential to directing changes in perioperative management that will reduce morbidity and improve the quality of patient care . MATERIAL S AND METHODS The National Surgical Quality Improvement Program ( NSQIP ) is a prospect i ve quality management initiative of 123 Veterans Affairs Medical Centers nationwide . The NSQIP collects clinical information , intraoperative data and outcomes on a wide variety of surgical procedures from multiple surgical disciplines . Since 1991 , 2,538 radical cystectomy procedures have been captured by the NSQIP . Modeling using logistic regression was performed to identify patient specific risk factors and perioperative process measures associated with postoperative morbidity . RESULTS Of the 2,538 subjects at least 1 postoperative complication developed in 774 ( 30.5 % ) . The most frequent complication was ileus ( 10 % ) . Several factors were associated with the development of a complication , including age , dependent functional status , preoperative dyspnea , preoperative acute renal failure , chronic steroid use , preoperative alcohol consumption , American Society of Anesthesiology score , use of general anesthetic , operative time , intraoperative blood requirement and surgeon level of training . CONCLUSIONS Morbidity remains high after cystectomy with 30.5 % of subjects experiencing at least 1 complication . Measurable patient specific risk factors and perioperative processes associated with postoperative morbidity following cystectomy are now delineated which allows for improved risk stratification , patient counseling , and the development of novel processes that may incrementally reduce risk and improve outcomes There are many papers comparing two antibiotic protocol s for the profilaxis of head and neck infections after laryngeal surgery . We present one prospect i ve and r and omised study in 60 patients comparing the efficacy of two protocol s. The comparison was between ceftriaxone versus the association of clindamicyn and gentamicyn . In our data base we included the risk factors for infection , the surgical approach , the duration of surgery and the patient characteristics . We observed an incidence of 28 % of infection , with a 23.3 % in the clindamicyn + gentamicyn group and a 33.3 % in the ceftriaxone group . The differences between the two groups were not statistically significant . In this study we observed a small difference between the amount of alcohol comsuption , the effectiveness of the surgical drainage , the surgical approach and the presence of wound infection . The difference was not statistical significant due to the small group of patients . The profilaxis was adequate for the total laryngectomy and cordectomy group , with a higher incidence of wound infection in patients treated with a supraglottic laryngectomy Study Design . This is a multivariate analysis of a prospect ively collected data base . Objective . To determine preoperative , intraoperative , and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing spinal surgery . Summary of Background Data . Current literature sites a postoperative infection rate of approximately 4 % ; however , few have completed multivariate analysis to determine factors which contribute to risk of infection . Methods . Our study identified patients who underwent a spinal decompression and fusion between 1997 and 2006 from the Veterans Affairs ’ National Surgical Quality Improvement Program data base . Multivariate logistic regression analysis was used to determine the effect of various preoperative variables on postoperative infection . Results . Data on 24,774 patients were analyzed . Wound infection was present in 752 ( 3.04 % ) patients , 287 ( 1.16 % ) deep , and 468 ( 1.89 % ) superficial . Postoperative infection was associated with longer hospital stay ( 7.12 vs. 4.20 days ) , higher 30-day mortality ( 1.06 % vs. 0.5 % ) , higher complication rates ( 1.24 % vs. 0.05 % ) , and higher return to the operating room rates ( 37 % vs. 2.45 % ) . Multivariate logistic regression identified insulin dependent diabetes ( odds ratios [ OR ] = 1.50 ) , current smoking ( OR = 1.19 ) ASA class of 3 ( OR = 1.45 ) or 4 to 5 ( OR = 1.66 ) , weight loss ( OR = 2.14 ) , dependent functional status ( 1.36 ) preoperative HCT < 36 ( 1.37 ) , disseminated cancer ( 1.83 ) , fusion ( OR = 1.24 ) and an operative duration of 3 to 6 hours ( OR = 1.33 ) or > 6 hours ( OR = 1.40 ) as statistically significant predictors of postoperative infection . Conclusion . Using multivariate analysis of a large prospect ively collected data from the National Surgical Quality Improvement Program data base , we identified the most important risk factors for increased postoperative spinal wound infection . We have demonstrated the high mortality , morbidity , and hospitalization costs associated with postoperative spinal wound infections . The information provided should help alert clinicians to presence of these risks factors and the likelihood of higher postoperative infections and morbidity in spinal surgery patients RATIONALE Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit ( ICU ) stay . Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal ( HPA ) axis and immunity . OBJECTIVES The aim of this study was to evaluate HPA intervention with low-dose ethanol , morphine , or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients . METHODS In this r and omized , double-blind controlled study , 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included . Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence . Nonalcoholic patients were included but only as a descriptive control . Perioperative intervention with low-dose ethanol ( 0.5 g/kg body weight per day ) , morphine ( 15 mug/kg body weight per hour ) , ketoconazole ( 200 mg four times daily ) , and placebo was started on the morning before surgery and continued for 3 d after surgery . Blood sample s to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1 , 3 , and 7 after surgery . MEASUREMENTS AND MAIN RESULTS In long-term alcoholic patients , all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio . All interventions decreased the pneumonia rate from 39 % to a median of 5.7 % and shortened intensive care unit stay by 9 d ( median ) compared with the placebo-treated long-term alcoholic patients . CONCLUSIONS Intervention at the level of the HPA axis altered the immune response to surgical stress . This result ed in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients BACKGROUND The purpose of this article is to describe the background , design , and patient population s of the Patient Safety in Surgery Study , as a preliminary to the articles in this journal that will report the results of the Study . STUDY DESIGN The Patient Safety in Surgery Study was a prospect i ve cohort study . Trained nurses collected preoperative risk factors , operative variables , and 30-day postoperative mortality and morbidity outcomes in patients undergoing major general and vascular operations at 128 Veterans Affairs ( VA ) medical centers and 14 selected university medical centers between October 1 , 2001 and September 30 , 2004 . An Internet-based data collection system was used to input data from the different private medical centers . Semiannual feedback of observed to expected mortality and morbidity ratios was provided to the participating medical centers . RESULTS During the 3-year study , total accrual in general surgery was 145,618 patients , including 68.5 % from the VA and 31.5 % from the private sector . Accrual in vascular surgery totaled 39,225 patients , including 77.8 % from the VA and 22.2 % from the private sector . VA patients were older and included a larger proportion of male patients and African Americans and Hispanics . The VA population included more inguinal , umbilical , and ventral hernia repairs , although the private-sector population included more thyroid and parathyroid , appendectomy , and operations for breast cancer . Preoperative comorbidities were similar in the two population s , but the rates of comorbidities were higher in the VA . American Society of Anesthesiologists classification tended to be higher in the VA . CONCLUSIONS The National Surgical Quality Improvement Program methodology was successfully implemented in the 14 university medical centers . The data from the study provided the basis for the articles in this issue of the Journal of the American College of Surgeons Despite improved surgical techniques there is still a risk of mortality in elective general surgery . In a prospect i ve study preoperative data from 3250 patients were collected and compared with postoperative systemic complications , using univariate χ2 analysis . Highly significant ( P < 0.00001 ) variables were subjected to stepwise logistic regression analysis . The severity of operative procedure , higher American Society of Anesthesiologists ( ASA ) grade , symptoms of respiratory disease and malignancy were found to be significant risk factors predicting postoperative morbidity ( P<0.05 ) . Using these four variables , a simple preoperative risk scoring system has been defined . Class A ( up to 5 points ) was defined as a low‐risk group ( systemic complication rate 5.0 per cent ) , class B ( 5–7 points ) was intermediate risk ( systemic complication rate 17.9 per cent ) and class C ( 8–10 points ) was high risk ( systemic complication rate 33.3 per cent ) . Patients at high risk for perioperative and postoperative complications are more likely to be identified by this analysis than by using the ASA classification alone A 10-year prospect i ve study undertaken at Foothills Hospital in Canada used the infection of wounds to measure the rate of infection on the surgical services . The authors consider the effects of the following factors on the rate of infection : length of preoperative stay , preparation of the patient for surgery , identification of patients at risk , surgical technique and choice of procedure , and acquainting staff with statistics of wound infection rates BACKGROUND We aim ed to determine predictors of morbidity in patients undergoing microvascular free flap reconstruction of the head and neck . METHODS We prospect ively evaluated 796 cases between 1999 and 2007 using univariate and multivariate analysis to determine predictors of morbidity and prolonged hospital stay . RESULTS Two hundred thirty-nine patients ( 30 % ) developed major complications . Age , body mass index ( BMI ) , American Society of Anesthesiology ( ASA ) score , Kaplan Feinstein comorbidity index ( KFI ) score , preoperative hemoglobin , and tracheostomy were independent predictors of major complication . Predictors of prolonged hospital stay included age , recent weight loss , alcohol excess , ASA , KFI , preoperative hemoglobin , mucosal surgery , anesthesia duration , and crystalloid replacement volume . CONCLUSION Several variables are associated with an increased risk of development of major complications following free flap reconstruction of the head and neck . Although many of these variables are irreversible , they aid risk stratification of patients undergoing free flap reconstruction , and assist clinicians in making treatment decisions , consenting , and providing patients with realistic expectations regarding their perioperative course |
2,110 | 24,560,482 | CONCLUSIONS Well- design ed clinical trials , of adequate sample size , are urgently needed to establish the safety , efficacy and acceptability of task sharing tubal sterilization to midlevel providers | BACKGROUND Task sharing is an important strategy for increasing access to modern , effective contraception for women and reducing unmet need for family planning .
OBJECTIVE The objective was to identify evidence for the safety , efficacy or acceptability of task sharing tubal sterilization to midlevel providers . | Background Clinical officers perform much of major emergency surgery in Malawi , in the absence of medical officers . The aim of this study was to vali date the advantages and disadvantages of delegation of major obstetric surgery to non-doctors . Methods During a three month period , data from 2131 consecutive obstetric surgeries in 38 district hospitals in Malawi were collected prospect ively . The interventions included caesarean sections alone and those that were combined with other interventions such as subtotal and total hysterectomy repair of uterine rupture and tubal ligation . All these surgeries were conducted either by clinical officers or by medical officers . Results During the study period , clinical officers performed 90 % of all straight caesarean sections , 70 % of those combined with subtotal hysterectomy , 60 % of those combined with total hysterectomy and 89 % of those combined with repair of uterine rupture . A comparable profile of patients was operated on by clinical officers and medical officers , respectively . Postoperative outcomes were almost identical in the two groups in terms of maternal general condition – both immediately and 24 hours postoperatively – and regarding occurrence of pyrexia , wound infection , wound dehiscence , need for re-operation , neonatal outcome or maternal death . Conclusion Clinical officers perform the bulk of emergency obstetric operations at district hospitals in Malawi . The postoperative outcomes of their procedures are comparable to those of medical officers . Clinical officers constitute a crucial component of the health care team in Malawi for saving maternal and neonatal lives given the scarcity of physicians To assess whether trained nursing personnel could provide IUD services as safely and effectively as physicians in Brazil , an experimental study was conducted at the main clinic of the Center for Research on Integrated Maternal and Child Care in Rio de Janeiro . From November 1984 through April 1986 , a total of 1,711 women who requested IUD insertion at the clinic were r and omly assigned to have a Copper-T 200 IUD inserted by one of the clinic 's 11 physicians or 13 nurses . All of the physicians and nursing staff members who provided these services had taken the Center 's st and ard clinical family planning training course . Of 860 insertions attempted by the physicians and nurses , 1.3 % and 3.3 % , respectively , were unsuccessful . Statistically , this difference was very significant ( P < 0.01 ) . Also , mainly because the cervix was small and undilated , nulliparous women had a relatively high insertion failure rate of 8.0 % , as compared to 1.5 % for primiparas and 1.0 % for multiparas . The overall rate of complications at insertion was 1.8 % , these complications including diaphoresis , vomiting , syncope , cervical laceration , and one case of perforation of the uterus ; no significant difference was found between the complication rates for insertions performed by physicians as compared to nurses . However , 9.0 % of the study subjects reported severe pain during IUD insertion , with significantly higher percentages reporting pain if the IUD was inserted by a physician , or if the subject was nulliparous , had preinsertion symptoms , or had a history of pelvic inflammatory disease ( PID ) or sexually transmitted disease ( STD ) . It was also found that the nurses had a dramatically high insertion failure rate ( 11.6 % ) with nulliparous subjects , while the physicians ' failure rate with such subjects was a significantly lower 3.4 % . No significant difference was found in the groups served by nurses and physicians with regard to postinsertion complaints or termination of use within 12 months of insertion . These findings suggest that future training , besides preparing nursing personnel in IUD insertion , should emphasize preparation in taking the client 's medical history and diagnosing existing medical symptoms that could be associated with IUD insertion complications . In addition , if a nulliparous woman requests an insertion , it should be performed by a physician or more experienced nursing staff member with close medical supervision . Because of high rates of reported pain at insertion , such women , as well as those with medical symptoms associated IUD insertion complications and those with a history of PID or STD , should be considered c and i date s for extra care and counseling . ( ABSTRACT TRUNCATED AT 400 WORDS A shortage of doctors limits the provision of post-partum sterilisation services in rural areas of Thail and . To overcome this problem nurse-midwives with theatre experience were trained to perform post-partum tubal ligation by a mini-laparotomy incision under local anaesthesia . The performance of the nurse-midwives was compared with that of doctors in a controlled , r and omised clinical trial . Some operative difficulty was encountered by the nurses in 4.9 % of cases and by the doctors in 2.0 % of cases . This difference is not statistically significant and arose largely because the nurse-midwife cases were more obese . Nurse-midwives required a significantly longer operating-time ( 18.5 min ) than doctors ( 11.9 min ) . However , postoperative morbidity was similar in the two groups ( 7.0 % and 6.0 % , respectively ) . These results suggest that trained nurse-midwives with theatre experience can safely provide post-partum sterilisation services . A further field trial is underway BACKGROUND Tubal sterilization is an increasingly common method of contraception in the United States . Although pregnancy after sterilization is uncommon , it can occur and may be ectopic . We used data from the U.S. Collaborative Review of Sterilization to estimate the risk of ectopic pregnancy in women who had undergone the common types of tubal sterilization . METHODS A total of 10,685 women undergoing tubal sterilization were followed in a multicenter , prospect i ve cohort study . We intended to follow all the women for 5 years by means of annual telephone interviews ; for women enrolled early in the study , we attempted an additional follow-up telephone interview 8 to 14 years after sterilization . To assess the risk of ectopic pregnancy in these women , we used cumulative life-table probabilities and proportional-hazards analysis . RESULTS There were 47 ectopic pregnancies in the 10,685 women ; the 10-year cumulative probability of ectopic pregnancy for all methods of tubal sterilization combined was 7.3 per 1000 procedures . The cumulative probability varied substantially according to the method of sterilization and the woman 's age at the time of sterilization . Women sterilized by bipolar tubal coagulation before the age of 30 years had a probability of ectopic pregnancy that was 27 times as high as that among women of similar age who underwent postpartum partial salpingectomy ( 31.9 vs. 1.2 ectopic pregnancies per 1000 procedures ) . The annual rate of ectopic pregnancy for all methods combined in the 4th through 10th years after sterilization was no lower than that in the first 3 years . CONCLUSIONS A history of tubal sterilization does not rule out the possibility of ectopic pregnancy , even many years after the procedure Several studies have shown that nurses , nurse midwives , and paramedical personnel can provide satisfactory IUD services , but restrictions are still placed upon their provision of these services . A r and omized trial of auxiliary nurse midwife and physician IUD services was conducted among 495 interval acceptors in Turkey and 510 postpartum acceptors in the Philippines between 1976 and 1979 to further evaluate this question . Discontinuations due to expulsion , removal , and pregnancy were comparable for physician and nurse midwife clients . Among Filipino women who experienced an early expulsion , nurse midwives reinserted a device in significantly more cases ( 54.5 % ) than physicians ( 31.3 % ) . The diagnosis of contraindications or complications were similar in the 2 groups . Turkish women frequently refused to have pelvic examinations by male physicians , and in the Philippines , nurse midwives provided better follow up than physicians . It is concluded that auxiliary nurse midwives can provide clinical services comparable to those provided by doctors , and may give better continuity of care because they are more accessible and acceptable to clients OBJECTIVE To compare the safety and quality of contraceptive injections by community-based health workers with those of clinic-based nurses in a rural African setting . METHODS A nonr and omized community trial tested provision of injectable Depo Provera ( DMPA ) by community reproductive health workers and compared it with routine DPMA provision at health units in Nakasongola District , Ug and a. The primary outcome measures were safety , acceptability and continuation rates . FINDINGS A total of 945 new DMPA users were recruited by community workers , clinic-based nurses and midwives . Research ers successfully followed 777 ( 82 % follow-up ) : 449 community worker clients and 328 clinic-based clients . Ninety-five percent of community-worker clients were " satisfied " or " highly satisfied " with services , and 85 % reported receiving information on side-effects . There were no serious injection site problems in either group . Similarly , there was no significant difference between continuation to second injection ( 88 % among clients of community-based workers , 85 % among clinic-going clients ) , nor were there significant differences in other measures of safety , acceptability and quality . CONCLUSION Community-based distribution ( CBD ) of injectable contraceptives is now routine in some countries in Asia and Latin America , but is practically unknown in Africa , where arguably the need for this practice is greatest . This research reinforces experience from other regions suggesting that well-trained community health workers can safely provide contraceptive injections Insertion of IUDs by trained non-physicians is increasing . This secondary analysis of TCu380A IUD acceptors collected at clinics in Nigeria , Turkey and Mexico involved 367 women ; 193 insertions were performed by physicians and 174 by non-physicians . Women having their IUD inserted by a non-physician were more likely to experience a pain-free insertion , but also likelier to have the IUD removed for bleeding and pain or to experience an expulsion than women who had their IUD inserted by a physician . Early discontinuation rates were similar between the two groups . Overall continuation rates were statistically higher for IUDs inserted by physicians only at the Mexico site . Trained non-physicians can probably safely insert the TCu380A IUD . Appropriate competency-based training is required to limit the number of expulsions and removals for bleeding and pain by non-physicians OBJECTIVE To assess safety associated with tubal ligation performed by trained clinical officers ( COs ) in rural Ug and a. METHODS Between March and June 2012 , 518 women in 4 regions of Ug and a were recruited into a prospect i ve cohort study and followed at days 3 , 7 , and 45 after undergoing tubal ligation performed by a trained CO . Intraoperative and postoperative adverse events ( minor , moderate , or major ) , and acceptability were assessed . RESULTS Mean age was 36 years ( range , 20 - 49 years ) and mean number of living children was 6.7 ( range , 0 - 15 ) . The overall rate of major adverse events was 1.5 % : 0.4 % intraoperatively ; 1.9 % at day 3 ; and 0.2 % at day 7 . The majority of women who underwent tubal ligation reported a good/very good experience at the facility ( range , 94%-99 % ) and would recommend the health services to a friend ( range , 93%-98 % ) . CONCLUSION In the present study , task sharing of tubal ligation to trained COs in private facilities was safe . Women reported high levels of satisfaction with the procedure . Training COs could be an effective strategy for exp and ing family-planning services to rural Ug and |
2,111 | 11,687,050 | No statistically significant effect was observed for fasting glucose , HbA1c , total or HDL cholesterol .
The triglyceride lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited people with hypertriglyceridemia and used higher doses of fish oil .
REVIEW ER 'S CONCLUSIONS Fish oil supplementation in type 2 diabetes lowers triglycerides , may raise LDL cholesterol ( especially in hypertriglyceridemic patients on higher doses of fish oil ) and has no statistically significant effect on glycemic control . | BACKGROUND People with type 2 diabetes mellitus are at increased risk from cardiovascular disease .
Dietary fish oils are known to reduce triglyceride levels , but their impact on cholesterol levels , glycemic control and vascular outcomes are not well known .
OBJECTIVES To determine the effects of fish oil supplementation on cardiovascular outcomes , cholesterol levels and glycemic control in people with type 2 diabetes mellitus . | In a double-blind , placebo-controlled study we investigated the effects of dietary fish oil supplementation on arterial wall characteristics in 20 patients with non-insulin-dependent diabetes mellitus . Estimates reflecting compliance values in the large arteries and more peripheral vasculature , as measured by pulse-contour analysis , improved significantly after 6 weeks of fish oil therapy compared with values recorded at baseline and after 6 weeks ' administration of olive oil . The large-artery compliance estimate increased from 1.50 ( confidence interval [ CI ] , 1.31 to 1.69 ) mL/mm Hg at baseline to 1.68 ( CI , 1.52 to 1.84 ) mL/mm Hg after fish oil administration ( P < .01 ) . The oscillatory compliance value increased from 0.015 ( CI , 0.011 to 0.019 ) mL/mm Hg at baseline to 0.022 ( CI , 0.016 to 0.028 ) mL/mm Hg after fish oil ingestion ( P < .05 ) . No changes occurred in arterial blood pressure , cardiac output , stroke volume , or systemic vascular resistance with either intervention . The improved compliance estimates with fish oil ingestion occurred without altering fasting blood glucose and cholesterol concentrations . These results support the hypothesis that fish oils alter vascular reactivity and favorably influence arterial wall characteristics in patients with non-insulin-dependent diabetes mellitus . These direct vascular effects , expressed at the level of the vessel wall , may contribute to the cardioprotective actions of fish oil in humans Summary This study was conducted to examine the effect of ω3 fatty acid supplementation on plasma lipid , cholesterol and lipoprotein fatty acid content of non-insulin-dependent diabetic individuals consuming a higher ( 0.65 , n = 10 ) or lower ( 0.44 , n = 18 ) ratio of dietary polyunsaturated to saturated fatty acid ( P/S ) . The participants were initially given an olive oil supplement ( placebo ) equivalent to 35 mg of 18:1 · kg body weight–1 · day–1 for 3 months . This was followed by two ω3 supplement periods in a r and omized crossover . In these 3-month periods , participants were given a linseed oil supplement equivalent to 35 mg of 18:3ω3 · kg body weight–1 · day–1 or a fish oil supplement equivalent to 35 mg of 20:5ω3 + 22:6ω3 · kg body weight–1 · day–1 . At the end of each supplement period , a blood sample was drawn from each participant for lipid , lipoprotein , insulin , glucagon and C-peptide analyses . At the end of each 3-month period a 7-day dietary record was completed to calculate dietary fat intake and P/S ratio . Results indicate that fish oil significantly reduced plasma triacylglycerol level ( p < 0.05 ) and increased 20:5ω3 and 22:6ω3 content of all lipoprotein lipid classes . Linolenic acid supplementation had no effect on plasma triacylglycerol level , but it increased 18:3ω3 content of lipoprotein cholesterol ester fractions ( p < 0.05 ) . A slight increase in 20:5ω3 , but not 22:6ω3 , content was noted in lipoprotein lipid classes as a result of 18:3ω3 supplementation . LDL and HDL cholesterol , insulin , glucagon and C-peptide levels were not affected by either ω3 supplement . It is concluded that a modest intake of ω3 fatty acids , such as could be obtained from consuming fish regularly , will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels . [ Diabetologia ( 1997 ) 40 : 45–52 BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration The short-term effect of high fiber intake on fish-oil treatment in 15 free-living , non-insulin-dependent diabetic patients was evaluated by using a controlled , sequential study design . During an 8-wk fish-oil-treatment period when patients received 20 g fish oil/d , the usual daily fiber intake was increased with a 15-g pectin supplement at midpoint . Fish oil alone lowered triacylglycerol and very-low-density-lipoprotein-cholesterol concentrations by 41 % and 36 % , respectively ( both P < 0.01 by the end of the treatment period ) with unchanged mean total , low-density- , and high-density-lipoprotein-cholesterol concentrations . When the fiber intake was increased , however , total and low-density-lipoprotein-cholesterol concentrations decreased significantly ( P < 0.001 and < 0.05 , respectively ) with fish-oil treatment . The cholesterol ester fraction of plasma lipids was reduced by 34 % when compared with fish oil alone ( P < 0.05 ) . The plasma triacylglycerol fraction decreased further by 44 % ( P < 0.001 ) . Other beneficial effects observed included a 30 % decline in the fatty acid fraction ( P < 0.002 ) by end of the treatment period . Diabetic control was maintained during the 12-wk study . In conclusion , a high fiber intake may be beneficial in fish oil-treated diabetic patients Fish-oil supplementation decreases serum triacylglycerols but may worsen hyperglycemia in patients with non-insulin-dependent diabetes mellitus . The reason for the possible deterioration of glycemia is unclear . We examined whether inhibition of triacylglycerol synthesis by n-3 fatty acids changes lipolysis , glycerol gluconeogenesis , or fatty acid oxidation . Nine obese patients with non-insulin-dependent diabetes mellitus participated in a r and omized double-blind crossover study in which 6 wk of n-3 fatty acid supplementation ( 12 g fish oil ) was compared with 6 wk of corn plus olive oil . Serum triacylglycerols decreased by 30 % during n-3 fatty acid supplementation . Glycerol gluconeogenesis ( [U-14C]glycerol ) increased by 32 % . However , overall glucose production ( [3 - 3H]glucose ) , glycemic control , and fatty acid oxidation remained unchanged . Thus , 6 wk of n-3 fatty acid supplementation lowers triacylglycerols in patients with non-insulin-dependent diabetes mellitus without worsening glycemic control . However , n-3 fatty acid supplementation increases glycerol gluconeogenesis , which could contribute to deterioration of glycemic control during long-term treatment with high doses of fish-oil supplements A multicenter , r and omized , double-blind , place-bo-controlled study evaluated the possible worsening of glycemic control after a moderate daily intake of n-3 fatty acid ethyl esters in patients with hypertriglyceridemia with and without glucose intolerance or diabetes . A total of 935 patients of both sexes in 63 Italian clinical centers were selected ; 55 % had either impaired glucose tolerance or non-insulin-dependent diabetes mellitus ( NIDDM ) . They received for 2 mo either 1 g n-3 ethyl esters three times a day or a corresponding placebo , followed by 4 mo of either 1 g n-3 ethyl esters twice a day or placebo . In addition to the complete lipid and lipoprotein evaluation , patients with impaired glucose tolerance also underwent an oral-glucose-tolerance test ; in patients with NIDDM , serum insulin and glycated hemoglobin ( Hb A1c ) concentrations were determined . Plasma triacylglycerol concentrations decreased significantly , up to 21.53 % at 6 mo compared with baseline ( decreased 15 % compared with placebo ) , with a tendency toward a progressive reduction with time . There was no evidence for a different response in patients with either NIDDM or impaired glucose tolerance . Among NIDDM patients , the triacylglycerol reduction was greater in those with high-density-lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major glycemic indexes : fasting glucose , Hb A1c , insulinemia , and oral glucose tolerance in patients with impaired glucose tolerance or NIDDM after treatment with n-3 ethyl esters . Treatment with a moderate daily dose of n-3 ethyl esters over a prolonged period of time significantly reduced triacylglycerol concentrations without any worsening of glucose tolerance in patients with hypertriglyceridemia with and without impaired glycemic regulation Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat , high complex carbohydrate diet . Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation ; plasma total and HDL cholesterol concentrations did not change . The LDL cholesterol level was significantly increased with fish oil supplementation , suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and /or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease . The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein ( LDL ) oxidation was examined in 20 treated hypertensive subjects . The r and omized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil . Fish oil significantly ( -24 % , P < 0.01 ) reduced plasma triglyceride , and increased LDL-cholesterol ( + 6 % , P < 0.01 compared to corn oil ) . LDL particles were larger ( P < 0.01 ) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride ( P < 0.001 ) both before and after fish oil supplementation , and positively correlated with high density lipoprotein cholesterol ( P < 0.01 ) . Fish oil reduced lag time before onset of copper-induced LDL oxidation ( -25 % , P < 0.001 ) and significantly increased production of thiobarbituric acid-reactive substances ( TBARS ) during oxidation , compared with corn oil . Corn oil had no significant effect on lag time and oxidation rate . Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL . Corn oil was without effect . Additionally , macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly ( P < 0.001 ) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids . We conclude that from the st and point of atherosclerosis , fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable OBJECTIVE To determine whether serum lipid intervention , in addition to conventional diabetes treatment , could alter cardiovascular outcomes in type 2 diabetes . RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects ( 117 men , 47 women ) without a history of clinical cardiovascular disease r and omized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospect ively for a minimum of 3 years . Serial biochemical and noninvasive vascular assessment s , carotid and femoral artery B-mode ultrasound measurements , and those pertaining to coronary heart disease (CHD)— clinical history , the World Health Organization ( WHO ) cardiovascular question naire , and resting and exercise electrocardiogram (ECG)—were recorded . RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride ( −32 vs. 4 % , P = 0.001 ) , total cholesterol ( −7 vs. −0.3 % , P = 0.004 ) , and total−to-HDL cholesterol ratio ( −12 vs. −0.0 % , P = 0.001 ) , and an increase in HDL cholesterol ( 6 vs. −2 % , P = 0.02 ) as compared with placebo . There was a trend toward a greater reduction of fibrinogen ( −18 vs. −6 % , P = 0.08 ) at 3 years . No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease . In those treated with bezafibrate , there was a significant reduction ( P = 0.01 , log-rank test ) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infa rct ion . CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease , although the lower rate of “ definite CHD events ” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease The metabolic effect of 3-week dietary supplementation with a fish oil concentrate was examined in not markedly obese , not hypertriglyceridemic men with non-insulin-dependent diabetes mellitus ( NIDDM ) treated with hypoglycemic agents . Ten patients were given 15 ml/d of fish oil ( Martens Oil , Norway ) equivalent to 3.1 g of n-3 fatty acid ( FA ) per day , and compared to 10 diabetics treated with placebo ( 15 ml/d saline ) . While fish oil leads to expected increase in the ratio of n-3 to n-6 FA intake , it does not alter fasting and mixed meal stimulated blood glucose , plasma insulin and C-peptide concentrations . There were no changes in insulin action estimated by the metabolic clearance rates of glucose at plasma insulin levels of about 100 microU/ml and 1400 microU/ml during hyperinsulinemic isoglycemic clamp , and no changes were seen in insulin binding to erythrocytes . Even though our short-term study does not warrant authoritative conclusions , no adverse effects of low-dose fish oil on glucose homeostasis have been found in not markedly obese NIDDM patients treated with oral hypoglycemics OBJECTIVE Supplementation of type II diabetic diets with n-3 fatty acids ( FAs ) from fish oil ( FO ) has been associated with lowered triglyceride and VLDL levels , although reports of impaired glycemic control have limited their use . Effects of n-3FAs from nonmarine sources are less well documented . Therefore , an investigation comparing the effects of linseed oil ( LO ) with FO supplementation was undertaken in subjects with type II diabetes . RESEARCH DESIGN AND METHODS Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a r and omized double-blind crossover fashion after 3 months of olive oil placebo . Oils were given as 35 mg FA · kg body wt−1 · day−1 . After each 3-month period , fasting glucose and insulin levels , HbA1c , lipid profiles , insulin sensitivity ( SI ) , glucose effectiveness ( SG ) , and acute insulin response to glucose ( AIRG ) were evaluated . RESULTS HbA1c and lipid values were within the normal range at r and omization . Repeated measures analysis of variance testing found no significant differences in weight ; fasting glucose and insulin levels ; HbA1c ; total , LDL , and HDL cholesterol levels ; SI ; SG ; or AIRG with either active oil . FO was associated with significant reductions in triglycerides and a trend toward decreased SI . CONCLUSIONS In a population with well-controlled type II diabetes , 3 months of FO but not LO result ed in lowered triglyceride levels . Neither LO nor FO significantly affected glycemic control , cholesterol values , SG , or insulin secretion , while a nonsignificant trend toward decreased insulin sensitivity was found with FO Non-insulin-dependent diabetes mellitus ( NIDDM ) is associated with elevated very-low-density lipoprotein ( VLDL ) triglyceride concentrations and abnormalities of low-density lipoprotein ( LDL ) composition . Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects , we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM . Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design . Medications , including antidiabetic therapy , were continued through the study . Compared with safflower oil treatment , fish oil supplementation result ed in a significant reduction of total plasma triglycerides of 24 % at the 4-g dose and a larger reduction of 39 % at the 7.5-g dose . These decreases were due to similar reductions in VLDL triglycerides . LDL cholesterol levels were mildly elevated , but a larger 20 % increase in LDL apolipoprotein B ( apoB ) concentration was observed . During supplementation with the fish oil concentrate , the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values , but not when compared with safflower oil treatment . Highdensity lipoprotein ( HDL ) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment . At the 7.5-g dose , fasting glucose and glycohemoglobin levels increased by 20 and 12 % , respectively , but were unchanged at the lower level of supplementation . Thus , in NIDDM patients , dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels . However , the observed increase in LDL apoB levels , and the deterioration in glycemic control , indicate thatfurther study will be required to establish whether fish oil has a role in the treatment of NIDDM Dietary cod-liver oil containing eicosapentaenoic acid is effective on microvascular albumin leakage in diabetic patients with albuminuria . We determined the long-term effects of oral pure eicosapentaenoic acid ethyl ( EPA-E : 900 mg/day ) administration on diabetic nephropathy in non-insulin dependent diabetic ( NIDDM ) patients . The effects of EPA-E were determined by observing the changes of the index of urine albumin excretion level/urine creatinine ( Cr ) excretion level ( UAI ) , the ratio of beta 2-microglobulin excretion level/urine Cr excretion level ( beta 2-MG/Cr ) and the ratio of N-acetyl-D-glucosaminidase excretion level/urine Cr excretion level ( NAG/Cr ) at 3 , 6 and 12 months after the start of the treatment . Oral EPA-E administration immediately improved the increased UAI at 3 months after the start of treatment . A significant improvement of the UAI by EPA-E was sustained 12 months later . EPA E administration also tended to decrease the urine beta 2-MG/Cr ratio from 6 months , but the difference was statistically not significant . However , the urine NAG/Cr ratio was not changed by EPA-E administration . EPA-E administration did not affect blood pressure levels , glycemic control and lipid metabolism in these patients . The present data indicated that EPA-E administration improved increased albumin excretion in NIDDM patients with nephropathy and its effects on albuminuria sustained for at least 12 months after the start of treatment . However , tubular factors were not influenced by EPA-E administration OBJECTIVE The triglyceride-lowering effects of ω-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM . However , fish oil may impair glycemic control in NIDDM . The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat ( 30 % total energy ) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients . RESEARCH DESIGN AND METHODS In a controlled , 8-week intervention , 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and /or HDL cholesterol < 1.0 mmol/l were r and omly assigned to a low-fat diet ( 30 % daily energy intake ) with or without one fish meal daily ( 3.6 g ω-3/day ) and further r and omized to a moderate ( 55–65 % VO2max ) or light ( heart rate < 100 bpm ) exercise program . An oral glucose tolerance test ( 75 g ) , fasting serum glucose , insulin , lipids , and GHb were measured before and after intervention . Self-monitoring of blood glucose was performed throughout . RESULTS In the 49 subjects who completed the study , moderate exercise improved aerobic fitness ( VO2max ) by 12 % ( from 1.87 to 2.07 l/min , P = 0.0001 ) . Fish consumption reduced triglycerides ( 0.80 mmol/l , P = 0.03 ) and HDL3 cholesterol ( 0.05 mmol/l , P = 0.02 ) and increased HDL2 cholesterol ( 0.06 mmol/l , P = 0.01 ) . After adjustment for age , sex , and changes in body weight , fish diets were associated with increases in GHb ( 0.50 % , P = 0.05 ) and self-monitored glucose ( 0.57 mmol/l , P = 0.0002 ) , which were prevented by moderate exercise . CONCLUSIONS A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients . Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise Summary Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease . Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations , principally by improving the release of nitric oxide from injured endothelium . Using forearm venous occlusion plethysmography we studied vascular responses to 60 , 120 , 180 and 240 nmol/min of acetylcholine ( an endothelium-dependent vasodilator ) and 3 , 6 and 9 nmol/min of glyceryl trinitrate ( an endothelium-independent vasodilator ) infused into the brachial artery in 23 patients with Type 2 ( non-insulin-dependent ) diabetes mellitus . NG monomethyl-l-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium . On completion of the baseline studies patients r and omly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase . Studies , identical to the initial baseline studies , were performed at the end of the active treatment periods at 6 and 18 weeks . Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration ( p<0.01 ) . Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies . NG monomethyl-l-arginine significantly reduced forearm blood flow from maximal stimulated values to acetylcholine when compared to the uninhibited decline in flow to acetylcholine infusions at comparable time points ( p<0.01 ) . Treatment with fish oils improved endothelium-dependent responses to acetylcholine without altering endothelium-independent responses to glyceryl trinitrate . By increasing stimulated nitric oxide release from the endothelium fish oils may afford protection against vasospasm and thrombosis in patients with diabetes mellitus OBJECTIVE To study the effects of a low dose of ω-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellus ( NIDDM ) . RESEARCH DESIGN AND METHODS We performed a r and omized , prospect i ve , double-blind , controlled study of a low dose of ω-3 fatty acids ( 2.5 g/day ) in 20 ambulatory subjects with NIDDM . Subjects ingested five 1-g fish oil capsules each containing 0.5 g ω-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period . RESULTS Nine subjects completed the study in each group . Both groups exhibited moderate control of glucose levels ; modest elevations in baseline total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and triglyceride ( TG ) levels ; and normal blood pressure values . In the fish oil group , plasma ω-3 fatty acid levels increased significantly . Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil . No difference was observed in collageninduced production of thromboxane A2 ( TXA2 , measured as the stable derivative TXB2 ) , or in adenosine-5'-diphosphate- ( ADP ) induced platelet aggregation or TXA2 generation . Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil . Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure ( sBP ) by 8 mmHg compared with safflower oil . Fish oil caused a significant but small increase in HbA1c ( 0.56 % ) and total cholesterol ( 20 mg/dl ) but had no effect on fasting glucose , high-density lipoprotein cholesterol , or LDL-cholesterol levels . CONCLUSIONS Small doses of fish oil inhibit platelet aggregation and TXA2 production , reduce upright sBP and TG levels , and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM . Small quantities of ω-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n-3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double-blind cross-over study during two consecutive 8-week periods . After MaxEPA treatment , there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids , while the n-6 fatty acid content decreased . The very low density lipoprotein ( VLDL ) triglyceride concentrations decreased significantly ( by 22 % ) on MaxEPA treatment . However , these changes were not significantly different from those observed during the placebo period . The blood glucose concentration tended to increase during MaxEPA treatment , and to decrease during the placebo period , the changes under the two regimes being significantly different ( P less than 0.01 ) . In addition , the rate constant for glucose disappearance ( k value ) for the intravenous insulin-tolerance test , which reflected the peripheral insulin sensitivity , tended to decrease during MaxEPA treatment and increase during administration of the placebo , there being a significant difference ( P less than 0.03 ) between the changes during the two treatments . The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear The effects of fish oil on lipoprotein subfractions and low density lipoprotein ( LDL ) size in non-insulin-dependent diabetes mellitus ( NIDDM ) patients with hypertriglyceridemia are unknown . To eluci date this , 16 NIDDM hypertriglyceridemic patients ( plasma triglyceride 2.25- 5.65 mmol/l , plasma cholesterol < or = 7.75 mmol/l ) were r and omly assigned to a 6-month period with either moderate amounts of fish oil ( n = 8) or placebo ( n = 8) after 4 weeks of wash-out and 3 weeks of run-in . Diet and hypoglycemic treatment were unchanged throughout the experiment . LDL size were evaluated at baseline and after 6 months . Three VLDL and LDL subfractions were measured at the end of the two periods . The total lipid concentration of all very low density lipoprotein ( VLDL ) subfractions was lower at the end of fish oil treatment compared with placebo ( large VLDL 124.3 + /- 19.7 mg/dl vs 156.7 + /- 45.5 mg/dl ; intermediate VLDL 88.5 + /- 9.5 mg/dl vs 113.9 + /- 23.2 mg/dl ; small VLDL 105.9 + /- 9.7 mg/dl vs 128.9 + /- 40.7 mg/dl ) ( mean + /- SEM ) , although the difference was not statistically significant . Moreover , at the end of the two treatments , the percentage distribution of VLDL subfractions was very similar ( large 37.5 + /- 3.3 % vs 37.6 + /- 2.6 % , intermediate 27.6 + /- 0.9 % vs 31.0 + /- 2.4 % ; small 34.9 + /- 3.7 % vs 31.4 + /- 2.1 % ) . Concerning LDL , no significant change in LDL size was observed after the two treatments ( 255.4 + /- 2.2 A vs 254.2 + /- 1.7 A , fish oil ; 253.7 + /- 2.0 A vs 253.3 + /- 1.7 A , placebo ) . LDL subfraction distribution was also very similar ( large 17 + /- 3 % vs 17 + /- 2 % ; intermediate 62 + /- 3 % vs 65 + /- 3 % ; small 21 + /- 3 % vs 18 + /- 2 % ) , at the end of the two periods , confirming the lack of effects on LDL size . In conclusion , our study indicates that in NIDDM patients with hypertriglyceridemia , fish oil does not induce any improvement in LDL distribution and LDL size despite its positive effects on plasma triglycerides OBJECTIVE To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus ( NIDDM ) . RESEARCH DESIGN AND METHODS Forty subjects ( 18 men and 22 women ; aged 53.9 ± 7.0 years ) with NIDDM and hyperlipidemia were r and omly assigned to one of four treatment groups : 9 g of fish oil , 18 g of fish oil , 9 g of corn oil , or 18 g of corn oil daily supplementation for 12 weeks . RESULTS The level of oil supplements ( 9 g compared with 18 g ) did not have a significant effect within each oil group on glycemic control and lipids . Significant differences ( P < 0.05 ) in lipids were found when the 9-g and 18-g groups were combined . In subjects consuming fish oil , plasma very-low-density lipoprotein ( VLDL ) cholesterol ( P = 0.0001 ) , plasma triglyceride ( TG ) ( P = 0.0001 ) , and plasma VLDL TGs ( P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks ) were significantly lowered compared with subjects consuming corn oil . Plasma VLDL cholesterol increased across time in the corn oil group ( P = 0.04 ) . Plasma low-density lipoprotein ( LDL ) cholesterol was temporarily increased ( P = 0.008 ) in the fish oil group at 6 weeks , but the effect was no longer present at 12 weeks . No significant differences between fish oil – or corn oil-supplemented diets were found in total plasma cholesterol , high-density lipoprotein cholesterol , fasting plasma glucose , glycosylated HbA1c , weight , and blood pressure . CONCLUSIONS In this study , fish oil supplementation improved plasma VLDL cholesterol , VLDL TGs , and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM . Furthermore , fish oil supplementation had no significant deleterious effect on glycemic control OBJECTIVE To examine the association of seal oil and salmon consumption with impaired glucose tolerance ( IGT ) and non-insulin-dependent diabetes mellitus ( NIDDM ) among Alaska Natives . RESEARCH DESIGN AND METHODS Screening was performed on 666 Yup'ik Eskimos and Athabaskan Indians ≥40 years old in 15 villages . Self-administered question naires were used to obtain partial food frequency data . A case was defined as IGT or NIDDM , either newly discovered or known . Newly discovered cases ( 11 patients with NIDDM and 17 with IGT ) were determined by r and om blood glucose testing followed by a 2-h 75-g oral glucose tolerance test ( OGTT ) for those with values ≥ 6.72 mmol/l or for subjects with unconfirmed histories of glucose intolerance . Known cases included 26 patients with NIDDM and 1 with IGT . Control subjects had r and om blood glucoses < 6.72 or normal OGTT results . RESULTS Compared with less-than-daily consumption , both daily seal oil ( odds ratio [ OR ] 0.2 , 95 % confidence interval [ CI ] 0.1–0.8 ) and daily salmon consumption ( OR 0.5 , CI 0.2–1.1 ) were associated with a lower prevalence of glucose intolerance , controlling for age , ethnicity , body mass index , and sex . The effects were similar when limited to newly discovered cases : OR 0.3 , CI 0.1–1.3 for seal oil and OR 0.4 , CI 0.1–1.3 for salmon . Consumption of seal oil at least five times per week was required to reduce risk . CONCLUSIONS Consumption of seal oil and salmon , high in ω-3 fatty acids , appears to lower the risk of glucose intolerance and is a potentially modifiable risk factor for NIDDM in Alaska Natives n-3 Fatty acids in the form of ethyl esters ( EE ) allow lower daily doses and improved compliance . Administration of n-3 fatty acids to patients with glucose intolerance has led to controversial findings , some studies indicating worsening of the disorder , others no effect , or an improvement . A total of 935 patients with hypertriglyceridemia , associated with additional cardiovascular risk factors , i.e. glucose intolerance , NIDDM and /or arterial hypertension were entered a double blind ( DB ) protocol lasting 6 months with n-3 EE versus placebo , followed by a further 6 months of open study ( n = 868 ) on 2 g a day of n-3 EE . At the end of the DB period , triglyceridemia in the total group was reduced significantly more by n-3 EE , without alterations in glycemic parameters . In the 6 months open follow up , patients on n-3 EE with type IIB hyperlipoproteinemia showed a significant reduction of total cholesterol , both in cases with ( -4.15 % vs. the 6 month levels ) and without NIDDM ( -3.8 % ) . HDL-cholesterol had an overall mean rise of 7.4 % , maximal in type IV patients with ( + 9.1 % ) and without ( + 10.1 % ) NIDDM . No alterations in glycemic parameters were detected in treated patients . Administration of n-3 EE to patients with hypertriglyceridemia associated with NIDDM or impaired glucose tolerance appears safe and effective Lipid peroxidation may be important in the development of cardiovascular disease , a common cause of mortality and morbidity in non-insulin dependent diabetes mellitus ( NIDDM ) . We assessed the degree of lipid peroxidation by measuring plasma malondialdehyde , as thiobarbituric acid reacting substances ( TBARS ) , in 23 non-insulin diabetic patients . Plasma levels of st and ardised alpha-tocopherol ( vitamin E ) , lipid content of whole plasma and lipoprotein fractions , glycosylated haemoglobin , glycosylated low density lipoprotein ( LDL ) and fasting blood glucose were also measured . On completion of the baseline studies patients r and omly received either fish oil or matching olive oil capsules in a double blind crossover fashion for 6 weeks followed by a 6 week washout period and a final 6 week treatment phase . Studies , identical to the initial baseline studies , were performed at the end of the of the active treatment periods at 6 and 18 weeks . Treatment with olive oil did not change levels of TBARS , vitamin E or indices of glycaemic control compared with baseline . Total cholesterol and triglyceride ( TG ) content of plasma and lipoprotein fractions were not significantly altered . Treatment with fish oil result ed in elevation of TBARS ( P < 0.001 ) and reduction of vitamin E ( P < 0.01 ) compared with baseline and olive oil treatment . Plasma cholesterol was unchanged . A reduction in plasma TG compared with baseline occurred but failed to reach significance ( P = 0.07 ) . Changes in apo B containing lipoproteins induced by fish oil failed to reach significance . No significant changes were observed in concentration or composition of high density lipoprotein ( HDL ) . Fish oil treatment showed no change in glycaemic control as assessed by glycosylated haemoglobin and LDL although a rise in fasting blood glucose just failed to reach significance ( P = 0.06 ) . Lipid peroxidation in NIDDM can be exacerbated by dietary fish oil . This potentially adverse reaction may limit the therapeutic use of fish oils in such patients Abstract . The effects of dietary supplementation with n‐3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non‐insulin‐dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n‐3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double‐blind cross‐over study during two consecutive 8‐week periods . The serum triglyceride ( TG ) concentrations decreased by 27 % ( P < 0.01 ) after addition of MaxEPA with a reduction of VLDL TG by 36 % ( P < 0.05 ) while LDL cholesterol increased by 6 % ( P= 0.05 ) . The fasting blood sugar and HbA1c . concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period . The highest glucose concentrations at fasting and after an i.v . glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged . The peripheral insulin sensitivity , as measured by a euglycaemic , hyperinsulinaemic clamp technique , did not change during the study . The mean plasminogen inhibitor‐1 ( PAI‐1 ) activity of the patients was elevated compared with healthy controls . In spite of the reduction of the triglyceride concentrations and unchanged insulin levels , there was a significant increase of the activity of PAI‐1 ( + 21 % , P < 0.01 ) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity . In many situations there seems to be a reduction of PAI‐1 when the triglycerides are lowered . In the diabetic patients given n‐3 fatty acids this was not the case OBJECTIVES The effect of a fish oil preparation , K-85 , in which the omega-3 fatty acid content was concentrated to 92 % of total fat , on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia . DESIGN The study was a r and omized , double-blind , placebo-controlled study . SETTING Seven centres participated in the study , five secondary referral centres and two general practice s. SUBJECTS Men and women aged 18 - 70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied . Patients with diabetes mellitus , hypothyroidism , serious illness in the previous 3 months or severe concurrent illness were excluded from the study , as were drug or alcohol abusers and pregnant and lactating women . Ninety-five subjects entered the study , 79 completed the study . INTERVENTIONS Patients were r and omized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks . MAIN OUTCOME MEASUREMENTS The serum concentrations of triglycerides and cholesterol , very low-density lipoprotein ( VLDL ) , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) and lipoprotein ( a ) . Fasting blood glucose and blood pressure . RESULTS Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6 , 10 and 14 weeks ( all P < 0.01 ) and there was a decrease in the serum triglyceride concentration from 3.99 ( 2.94 - 9.47 ) to 2.87 ( 1.2 - 9.93 ) mmol/l ( P < 0.001 ) and in VLDL-cholesterol from 1.47 ( 0.77 - 3.63 ) to 1.12 ( 0.21 - 3.67 ) mmol/l ( P < 0.01 ) in patients receiving K-85 . Serum HDL-cholesterol increased from 0.98 ( 0.95 - 1.01 ) to 1.11 ( 1.07 - 1.15 ) mmol/l ( P < 0.01 ) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb . Serum LDL-cholesterol , lipoprotein ( a ) and fasting blood glucose were unaffected by K-85 . Diastolic blood pressure decreased from 86 + /- 11 to 80 + /- 12 mmHg ( P < 0.02 ) and was also lower than in the placebo group ( P < 0.05 ) . The corn oil placebo did not affect any of the parameters . CONCLUSION K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospect i ve cohort study of 21,185 US male physicians who are participants in the Physicians ' Health Study . In 4 years of follow-up , there were 281 incident cases of total ( fatal and nonfatal ) myocardial infa rct ion , 173 cases of stroke , and 121 cardiovascular deaths . There was no evidence for association between dietary intake of fish and any cardiovascular endpoint , including myocardial infa rct ion , stroke , and cardiovascular death . The relative risks of total myocardial infa rct ion , adjusted for age and r and omized treatment assignment , for categories of fish intake were : 1.0 for < 1 meal/week ( referent ) , 1.6 ( 95 % confidence interval ( Cl ) 1.1 - 2.3 ) for 1 fish meal/week ; 1.4 ( 95 % Cl 1.0 - 2.0 ) for 2 - 4 fish meals/week ; and 1.2 ( 95 % Cl 0.6 - 2.2 ) for > or = 5 fish meals/week ; chi 2 for trend = 0.9 , p = 0.34 . The relative risks were similar for omega 3 fatty acid intake and for specific types of fish , and did not change after adjustment for history of hypertension , hypercholesterolemia , diabetes mellitus , or angina pectoris , parental history of myocardial infa rct ion before age 60 years , obesity , exercise , smoking , alcohol use , saturated fat intake , and vitamin supplement use . These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease The use of lipid-lowering drugs is now established clinical practice . However , not all patient categories have been covered in the l and mark studies ( 4S , WOSCOPS and CARE ) , leaving the arena open for widely differing opinions . Dyslipidoemia in patients with diabetes mellitus and arteriosclerotic disease of the aorta , limb arteries or carotid arteries should be corrected . The benefit remains unproven for patients with coronary artery disease and normal lipid levels , and for the elderly . Omega-3 supplements are approved in Norway for hypertriglyceridoemia , but clinical benefit has not been established for this treatment , in contrast to treatment with gemfibrosil . Hormone replacement therapy for postmenopausal women effectively lowers LDL cholesterol levels and the results of r and omised studies with clinical endpoints are awaited . The rapid effect ( within six months ) of lowered cholesterol on coronary events suggests that starting treatment during middle age is adequate for many patients , except for those with familial hyperlipidemias OBJECTIVE To assess the effects of low-dose eicosapentaenoic acid-ethyl-ester on diabetes regulation , lipid metabolism , blood rheology , and platelet reactivity . RESEARCH DESIGN AND METHODS In a double-blind , r and omized , placebo-controlled study , 24 NIDDM subjects received 1800 mg of EPA-E , 900 mg of EPA-E , or a placebo ( 1656 mg olive oil ) daily for 8 wk . RESULTS The EPA : arachidonic acid plasma ratio increased over an 8-wk period , then declined after a 4-wk wash-out period in the fish-oil groups in a dosedependent way . Platelet-activating factor-induced platelet aggregation decreased from 75 ± 7 % at wk 0 to 35 ± 21 % at wk 8 in the 900-mg group ( P = 0.016 ) and from 72 ± 11 to 40 ± 30 % in the 1800-mg group ( P = 0.039 ) , but did not change in the placebo group . No effects on A DP- or collagen-induced aggregation could be attributed to EPA-E. In the 1800-mg group low-density-lipoprotein cholesterol increased significantly , without concomitant rise in apolipoprotein B. Triglycerides , glycemic control , lipoprotein ( a ) , blood and plasma viscosity , erythrocyte deformability , and platelet adhesion to and aggregate formation on extracellular endothelial cell matrix were not significantly influenced . CONCLUSIONS Purified EPA-E in doses of 900 and 1800 mg reduces Plateletactivating factor-induced platelet aggregation without negatively affecting glycemic control . Low-density-lipoprotein cholesterol was elevated in the 1800-mg group We investigated the efficacy of fish oils in Portuguese patients with hypertriglyceridaemia and mixed hyperlipidaemia , and the influence of fish consumption on the triglyceride lowering capacity of fish oils . Forty patients participated in this double-blind study , consisting of a 4-week dietary or wash-out baseline period after which patients were r and omly assigned to receive either 12 fish oil capsules ( 3.6 g/day of omega 3 ) or similar 12 soya oil capsules per day for a period of 2 months . There were no statistically significant changes of total , HDL or LDL-cholesterol , and triglycerides . Nevertheless , triglycerides increased 19.9 % with soya oil and decreased 27.8 % with fish oils . Also , there was an inverse relationship ( rho = -0.352 ) between fish consumption and fish oils effect on triglycerides , and the triglyceride lowering with fish oils increased ( from 27.8 % to 44.4 % ) , reaching borderline significance , if we excluded patients consuming one or more meals with fish per day . Glucose increased 11 % ( P = 0.0047 ) with fish oils . These findings suggest that the triglyceride lowering effect of fish oils is affected by fish consumption , and confirm that fish oils increase blood glucose levels in diabetics and non-diabetics OBJECTIVE To assess in diabetic patients with coronary heart disease ( CHD ) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events . RESEARCH DESIGN AND METHODS A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infa rct ion or angina pectoris , serum total cholesterol 5.5–8.0 mmol/l , and serum triglycerides ≤ 2.5 mmol/l who were participating in the Sc and inavian Simvastatin Survival Study ( 4S ) . Participants in the 4S were r and omly assigned to double-blind treatment with simvastatin , 20 mg daily , with blinded dosage titration up to 40 mg daily , according to cholesterol response during the first 6–18 weeks , or placebo . Endpoints were 1 ) total mortality , 2 ) major CHD events ( CHD death or nonfatal myocardial infa rct ion ) , 3 ) other acute atherosclerotic events , 4 ) myocardial revascularization procedures . RESULTS Over the 5.4-year median follow-up period , simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients . The relative risks ( RRs ) of main endpoints in simvastatin-treated diabetic patients were as follows : total mortality 0.57 ( 95 % CI , 0.30–1.08 ; P = 0.087 ) , major CHD events 0.45 ( 95 % CI , 0.27–0.74 ; P = 0.002 ) , and any atherosclerotic event 0.63 ( 95 % CI , 0.43–0.92 ; P = 0.018 ) . The corresponding RRs in nondiabetic patients were the following : 0.71 ( 95 % CI , 0.58–0.87 ; P = 0.001 ) , 0.68 ( 95 % CI , 0.60–0.77 ; P < 0.0001 ) , and 0.74 ( 95 % CI , 0.68–0.82 ; P < 0.0001 ) . CONCLUSIONS The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD . The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events To compare the impact of dietary fish oil supplementation ( FO , 22 ml daily , containing 4.6 g of n-3 ( omega-3 ) fatty acids , equalling 14.4 mmol ) on carbohydrate and lipid metabolism with that of conventional lipostatic therapy ( Gemfibrozil ( G ) , 900 mg daily , equalling 3.6 mmol ) on hyperlipidemic non-insulin dependent diabetes mellitus ( NIDDM ) , 10 patients were selected for a r and omized , short-time , cross-over study . Each patient was treated for a duration of 2 weeks , with an individual washout period of 8 weeks . Metabolic variables and intravenous glucose tolerances ( 1.2 mmol/kg body weight , t = 30 min ) were determined on days 1 and 15 of each treatment period . Plasma lipid concentrations were identical at baseline , but were reduced more markedly following G as against FO exposure ( % change vs. baseline : total cholesterol ( chol ) , - 13**/-6 * ( G vs FO : p = 0.05 ) ; total triglycerides ( TG ) , -39**/-18 * * ( p < 0.05 ) ; APO B , -17**/- 10 * ( N.S. ) ; LDL-chol , -15**/0 ( p < 0.02 ) ; VLDL-chol , -50***/- 34 * * * ( N.S. ) ; VLDL-TG , -44***/-27 * * ( N.S. ) ; ( p vs. baseline : * < 0.05 , * * < 0.01 , * * * < 0.001 ) . Total-HDL , HDL2 , HDL3 and APO A were not influenced by either FO or G. Neither FO nor G induced a change in intravenous glucose tolerances or associated basal and incremental concentrations of insulin and C-peptide . We concluded , based on short-time applications , that ( a ) neither treatment affected the carbohydrate metabolism in patients with NIDDM , and ( b ) a greater hypolipidemic efficacy had to be assigned to Gemfibrozil than to fish oil . It would therefore appear that Gemfibrozil acts as a useful lipostatic pharmacologic compound , whilst fish oil could serve as a potential ingredient of a prudent cardio-protective diet which favours the low plasma triglyceride concentrations found in NIDDM patients OBJECTIVE The aim of this study was to evaluate the long-term ( 6-month ) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia . RESEARCH DESIGN AND METHODS The study has been performed according to a r and omized double-blind placebo-controlled design with a parallel group sequence . After a washout period of 4 weeks and a run-in period of 3 weeks , 16 NIDDM patients with hypertriglyceridemia ( triglyceride [ TG ] , 2.25–5.65 mmol/l ) were r and omly assigned to either fish oil ( 2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months , then 1.7 g/day for 4 more months ) ( n = 8) or placebo ( n = 8) . Diet and hypoglycemic drugs remained unchanged throughout the whole experiment . At baseline and after 6 months , insulin sensitivity was measured by euglycemic hyperinsulinemic clamp ( insulin infused , 2.0 mIU · kg−1 body wt · min−1 ) . At the same time , blood glucose control , fasting and postpr and ial serum insulin and nonesterified fatty acid ( NEFA ) concentrations , and fasting plasma lipoprotein concentrations were evaluated . RESULTS In the group treated with ffish oil compared with the baseline , there was : 1 ) a significant reduction in both plasma TG ( 2.92 ± 0.23 vs. 3.85 ± 0.32 [ mean ± SE ] mmol/l , P < 0.001 ) and VLDL-TG ( 2.35 ± 0.24 vs. 4.25 ± 0.66 mmol/l , P < 0.01 ) , without significant changes in blood glucose control ; 2 ) a significant reduction in fasting NEFA concentrations ( 572 ± 100 vs. 825 ± 131 μmol/l , P < 0.01 ) ; and 3 ) a significant enrichment in long-chain ω-3 fatty acids of erythrocyte membrane phospholipids . In the placebo group , there were no changes in any of the variables analyzed . The insulin-mediated glucose uptake was unchanged in both groups ( fish oil , 4.04 ± 0.82 mg · kg−1 · min−1 at baseline and 3.96 ± 0.50 mg · kg−1 · min−1 at 6 months ; placebo , 3.51 ± 0.62 mg · kg−1 · min−1 at baseline and 4.09 ± 0.49 mg · kg−1 · min−1 at 6 months ) . CONCLUSIONS In NIDDM patients with hypertriglyceridemia , moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides , VLDL triglycerides , and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain ω-3 fatty acids , without deteriorating blood glucose control . However , this amount of ω-3 fatty acids was unable to improve insulin sensitivity in this group of patients The long-term influence of n-3 polyunsaturated fatty acids ( n-3 PUFAs ) on serum lipids and glucose homeostasis was studied in a group of non-diabetic , moderately hypertriglyceridaemic patients undergoing coronary artery bypass grafting . They were investigated according to the same procedure before and 6 months after the operation . Following r and omization postoperatively , 28 patients received 3.4 g eicosapentaenoic and docosahexaenoic acid per day , whereas 29 patients comprised the control group . The decline in serum triglycerides after 6 months was significantly greater in the n-3 PUFA group than in the control group ( median decline , -33.2 % vs. -11.1 % , p = 0.002 ) , while no group difference was noted in serum total , HDL , or LDL cholesterol levels . Fasting plasma glucose levels decreased less in the n-3 PUFA group compared with the control group ( median change , -0.2 mmol l-1 vs. -0.5 mmol l-1 , p = 0.054 ) . The corresponding changes in fasting insulin levels were -2 mIU ml-1 in the n-3 PUFA group and no change in the control group ( p = 0.039 ) . In both groups combined , the recorded changes in serum triglyceride and serum insulin levels were negatively correlated with the change in serum phospholipid n-3 fatty acids ( r = -0.35 , p = 0.008 and r = -0.32 , p = 0.016 , respectively ) . An oral glucose tolerance test revealed no significant group differences after 6 months , neither in the peak levels , nor in the areas under the curves between 0 and 3h after the glucose load for glucose , insulin , and C-peptide . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Recent studies in nondiabetic kidney diseases suggest that dietary supplementation with n-3 polyunsaturated fatty acids ( fish oil ) may have beneficial effects on albuminuria , kidney function , arterial blood pressure , and dyslipidemia . Therefore , we evaluated the long-term effect of fish oil in diabetic nephropathy . RESEARCH DESIGN AND METHODS A 1-year double-blind r and omized controlled study comparing fish oil ( 4.6 g n-3 fatty acids/day ) with placebo ( olive oil ) was performed in an outpatient clinic in a tertiary referral center . Thirty-six normotensive IDDM patients with diabetic nephropathy were included ; 18 were treated with fish oil . Seven patients dropped out ( four received fish oil ) , and results for the remaining 29 are presented . Albuminuria ( enzyme immunoassay ) , glomerular filtration rate ( 51Cr-labeled EDTA plasma clearance ) , 24-h ambulatory blood pressure , and lipid profile were determined every 6 months . RESULTS Albuminuria increased by 22 % ( 1–46 % ) ( mean [ 95 % CI ] ) in the fish oil group vs. 15 % ( −11–49 % ) in the placebo group ( NS ) . Glomerular filtration rate decreased from 116 ± 7 to 105 ± 7 ml · min−1 · 1.73 m−2 ( mean ± SE ) vs. from 108 ± 6 to 103 ± 7 , fish oil and placebo , respectively ( NS ) . No significant changes occurred in 24-h ambulatory blood pressure : from 141 ± 4/82 ± 2 mmHg to 142 ± 5/83 ± 2 vs. from 140 ± 4/78 ± 2 to 144 ± 4/80 ± 3 , fish oil and placebo , respectively ( NS ) . In the fish oil group , serum triglycerides ( median [ range ] ) decreased from 0.97 ( 0.5–4.0 ) mmol/l to 0.8 ( 0.4–3.0 ) vs. from 1.01 ( 0.4–2.0 ) to 1.09 ( 0.4–2.0 ) in the placebo group ( P < 0.05 ) and VLDL cholesterol decreased from 0.45 ( 0.23–1.88 ) to 0.37 ( 0.21–1.43 ) mmol/l vs. from 0.44 ( 0.21–0.94 ) to 0.41 ( 0.17–1.94 ) ( P < 0.05 ) , but total and LDL cholesterol rose in the fish oil compared with the placebo group . CONCLUSIONS Our study does not suggest that fish oil has beneficial effects on albuminuria , kidney function , blood pressure , and dyslipidemia in normotensive IDDM patients suffering from diabetic nephropathy The aim of this study was to evaluate the effects of a fish oil preparation ( MaxEPA ) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic ( NIDDM ) subjects . Eighty NIDDM out patients aged 55.9 yr ( mean SD 11.5 yr ) participated in a prospect i ve double-blind placebo-controlled study of MaxEPA capsules ( 10 g/day ) or olive oil ( control ) treatment over 6 wk . Patients received either MaxEPA or olive oil in addition to preexisting therapy . Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk . Platelet membrane eicosapentaenoic acid ( EPA ) content increased in the treatment group ( P < 0.001 ) . MaxEPA supplementation was associated with a significant fall in total triglycerides ( P < 0.001 ) but did not affect total cholesterol ( P = 0.7 ) compared with control treatment . Fasting plasma glucose increased after 3 wk ( P = 0.01 ) but not after 6 wk ( P = 0.17 ) treatment with MaxEPA . Spontaneous platelet aggregation in whole blood fell in the MaxEPA group ( P < 0.02 ) after 6 wk , but there were no changes in agonist-induced platelet aggregation , thromboxane generation in platelet-rich plasma , or plasma P-thromboglobulin and platelet factor IV levels . An increase in clotting factor VII ( P = 0.02 ) , without changes in fibrinogen or factor X levels , occurred in the MaxEPA group . Similar reductions in blood pressure were observed in both groups . Dietary supplementation with MaxEPA capsules ( 10 g/day ) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels . Most indices of platelet function are unaffected by this therapy |
2,112 | 29,897,635 | At present , we can not draw reliable conclusions based on r and omized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy .
Full publication of the results from the studies may clarify the benefits of iridotomy | BACKGROUND Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle .
Obstruction of the anterior chamber angle blocks drainage of fluids ( aqueous humor ) within the eye and may raise intraocular pressure ( IOP ) .
Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss .
Laser peripheral iridotomy ( often just called ' iridotomy ' ) is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber through use of a laser to create a hole in the iris .
It is commonly used to treat patients with primary angle-closure glaucoma , patients with primary angle closure ( narrow angles and no signs of glaucomatous optic neuropathy ) , and patients who are primary angle-closure suspects ( patients with reversible obstruction ) .
The effectiveness of iridotomy on slowing progression of visual field loss , however , is uncertain .
OBJECTIVES To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma , primary angle closure , and primary angle-closure suspects . | PURPOSE To assess the short-term effect of laser peripheral iridotomy ( LPI ) on anterior segment anatomy in angle-closure suspects using ultrasound biomicroscopy ( UBM ) . DESIGN Prospect i ve intervention study . PARTICIPANTS Persons identified as angle-closure suspects aged 50 - 79 years from a population -based survey in Guangzhou , China . INTERVENTION Laser peripheral iridotomy was performed on 1 r and omly selected eye . Ultrasound biomicroscopy examination was carried out before and 2 weeks after the intervention . MAIN OUTCOME MEASURES Proportion of eyes with iridotrabecular contact ( ITC ) , as well as changes in UBM parameters including angle opening distance ( AOD ) , iris thickness ( IT ) , iris curvature , iris ciliary process distance , trabecular-ciliary process distance ( TCPD ) , and scleral spur to iris insertion distance ( SS-IR ) . RESULTS A total of 72 of 101 eligible subjects participated in the study . The proportion of people with UBM-identified ITC in > or = 1 quadrant dropped from 95 % ( 68/72 ) before to 59 % ( 42/72 ) after LPI . After LPI , the mean AOD at 250 microns increased from 0.064 mm ( st and ard deviation [ SD ] , 0.052 ) to 0.085 ( 0.052 ) mm ( P<0.001 ) ; angle recess area increased from 0.040 ( 0.030 ) to 0.070 ( 0.036 ) mm2 ( P<0.0001 ) ; TCPD increased from 0.537 to 0.561 mm ( P = 0.001 ) ; IT at 750 microns increased from 0.440 to 0.459 mm ( P = 0.094 ) , and IT at 1000 microns increased from 0.471 to 0.488 mm ( P = 0.0001 ) . Eyes whose angles remained closed after LPI ( pigmented trabecular meshwork not visible in > or =3 quadrants ) tended to have shallower AOD both at 250 ( 0.071 vs. 0.049 mm ; P = 0.09 ) and 500 microns ( 0.108 vs. 0.052 mm ; P = 0.001 ) , a thicker iris ( IT at 750 microns , 0.447 vs. 0.415 mm ; P = 0.041 ) , a more anterior positioned ciliary body ( TCPD , 0.514 vs. 0.562 mm ; P = 0.03 ) , and a statistically nonsignificant more anterior iris insertion ( SS-IR : 0.085 vs. 0.125 mm ; P = 0.061 ) , before LPI . CONCLUSIONS Laser peripheral iridotomy results in a significant increase in the angle width in Chinese people with narrow angles . However , some iridotrabecular contact was found in 59 % of eyes with a patent iridotomy . This was associated with smaller anterior chamber angle dimensions and a thicker iris , both of which may play a causative role in maintaining angle closure after LPI AIM To compare visual acuity and intraocular pressure outcomes 3 years after treatment of acute angle closure glaucoma ( AACG ) by operative peripheral iridectomy ( PI ) or Nd : YAG laser iridotomy ( YAG PI ) . METHODS A prospect i ve study of consecutive patients presenting to one ophthalmology department with uniocular AACG during a 2 year period . Following informed consent patients were r and omised to bilateral PI or bilateral YAG PI . Three years after treatment the mean Snellen visual acuity converted to logMAR scores of the two groups was compared using the unpaired Student ’s ttest . The number of patients with normal intraocular pressure with no further treatment in each group was compared using the χ2test with Yates ’s correction . RESULTS 21 patients underwent bilateral PI and 27 bilateral YAG PI . Three years after treatment visual acuity was 0.30 ( SD 0.28 ) log MAR units for PI eyes and 0.57 ( 0.67 ) logMAR units for YAG PI eyes ( p=0.08 , NS ) . 15 ( 70.4 % ) PI eyes and 19 ( 71.8 % ) YAG PI eyes had an intraocular pressure less than 21 mm Hg with no further treatment ( NS ) . CONCLUSIONS There was no significant difference in visual acuity or intraocular pressure control 3 years after treatment of AACG with PI or YAG PI PURPOSE Novel anterior segment optical coherence tomography ( ASOCT ) parameters associated with angle closure include anterior chamber area ( ACA ) , anterior chamber volume ( ACV ) , anterior chamber width ( ACW ) , lens vault ( LV ) , iris thickness ( IT ) , iris area ( I-area ) , and iris curvature ( I-curv ) . We aim ed to investigate changes in these parameters after laser peripheral iridotomy ( LPI ) in a cohort of primary angle-closure suspects ( PACS ) . DESIGN Prospect i ve observational study . PARTICIPANTS AND CONTROLS A total of 176 PACS aged ≥ 50 years who underwent LPI in 1 eye . METHODS We analyzed ASOCT images ( Visante , Carl Zeiss Meditec , Dublin , CA ) from all subjects using customized software before and 1 week after LPI . Multivariate linear regression analysis was performed for predictors of percentage change in mean angle opening distance ( AOD750 ) . MAIN OUTCOME MEASURES Change in ASOCT parameters after LPI . RESULTS The mean age of participants was 63 ± 7.3 years . The majority of subjects were Chinese ( 95.5 % ) and women ( 76.7 % ) . Mean angle width ( modified Shaffer grade ) changed from 0.68 ± 0.54 at baseline to 1.76±0.69 after LPI ( P<0.001 ) with a corresponding increase in mean AOD500 ( 0.12 vs. 0.19 mm , P<0.001 ) , trabecular iris surface area ( TISA500 , 0.06 vs. 0.08 mm(2 ) , P<0.001 ) , and angle recess area ( ARA , 0.13 vs. 0.17 mm(2 ) , P<0.001 ) . Mean ACA ( 15.0 vs. 16.0 mm(2 ) , P<0.001 ) and ACV ( 91.6 vs. 103.0 mm(3 ) , P<0.001 ) increased significantly after LPI , but there was no change in ACW , anterior chamber depth ( ACD ) , or LV . Mean I-curv was reduced ( 0.375 vs. 0.18 mm , P<0.001 ) after LPI , but there was no significant change in IT or I-area . After multivariate analysis , mean LV ( β = 0.286 , P = 0.001 ) , mean IT at 2000 μm ( IT2000 , β = 0.172 , P = 0.034 ) , and intraocular pressure ( β = 0.159 , P = 0.042 ) at baseline were found to be associated with ΔAOD750 . CONCLUSIONS This study confirms that LPI results in a significant increase in the angle width in PACS . The ACA and ACV increased after LPI , but there was no change in ACD , ACW , LV , IT , or I-area . The increase in ACA/ACV was mainly due to decreased I-curv after LPI PURPOSE To determine the prevalence of plateau iris in a cohort of primary angle closure suspects ( PACSs ) using ultrasound biomicroscopy ( UBM ) . DESIGN Cross-sectional observational study . PARTICIPANTS Subjects over the age of 50 years diagnosed as PACSs . INTERVENTION Subjects were r and omized to undergo laser peripheral iridotomy ( LPI ) in one eye . Ultrasound biomicroscopy was performed before and a week after LPI . MAIN OUTCOME MEASURES Ultrasound biomicroscopy images were qualitatively assessed using st and ardized criteria . Plateau iris was defined in a quadrant by the presence of an anteriorly directed ciliary body , an absent ciliary sulcus , a steep iris root from its point of insertion followed by a downward angulation from the corneoscleral wall , presence of a central flat iris plane , and irido-angle contact . At least 2 quadrants had to fulfil the above criteria for an eye to be defined as plateau iris . RESULTS Two hundred five subjects were enrolled ; UBM images of 167 subjects were available for analysis . Plateau iris was found in 54 of 167 ( 32.3 % ) PACS eyes after LPI . Quadrantwise analysis showed that 44 of 167 ( 26.3 % ) eyes had plateau iris in 1 quadrant , 36 ( 21.5 % ) in 2 quadrants , 16 ( 9.5 % ) in 3 quadrants , and 2 ( 1.2 % ) in all 4 quadrants . Plateau iris was most commonly observed in the superior and inferior quadrants . CONCLUSIONS Using st and ardized UBM criteria , plateau iris was found in about a third of PACS eyes after LPI . Prospect i ve longitudinal studies are required to determine the clinical significance of this finding for the management of PACSs Purpose : To summarize the design and methodology of a large-scale trial in southern China , the Zhongshan Angle Closure Prevention ( ZAP ) trial . This trial will determine if laser iridotomy ( LI ) is superior to no treatment for managing Chinese people who are Primary Angle Closure Suspects ( PACS ) . In this trial , PACS was defined as having 6 or more clock hours of angle circumference in which the pigmented trabecular meshwork was not visible under static gonioscopy in both eyes without elevated intraocular pressure , peripheral anterior synechiae or glaucomatous neuropathy . Methods : Subjects were recruited from an urban district in Guangzhou . The target sample size was 870 . Persons 50 years of age and older with 20/40 or better vision in both eyes identified as having 6 or more clock hours of angle circumference in which the pigmented trabecular meshwork was not visible under static gonioscopy in both eyes were enrolled . Each subject was r and omized to undergo LI in one eye with the fellow eye left untreated . Follow up is planned for a minimum period of 3 years . Baseline examination included tonometry , limbal chamber depth grading , gonioscopy , fundus photography , anterior segment coherence tomography , ultrasound A scan , ultrasound biomicroscopy , specular microscopy and dark room provocative testing . Endpoints for the study include developing elevated intraocular pressure , peripheral anterior synechiae or experiencing acute primary angle closure . Conclusion : The ZAP trial will determine if LI is safe and effective at preventing pathological angle closure in asymptomatic eyes with narrow angle configurations on gonioscopy . It will also provide data on what happens to untreated eyes in PACSs . Data collected at baseline will also help identify those at high risk for developing primary angle closure and primary angle closure glaucoma Aims To determine if screening with an ultrasound A-scan and prophylactic treatment of primary angle closure ( PAC ) with laser peripheral iridotomy ( LPI ) can reduce the incidence of primary angle closure glaucoma ( PACG ) in Mongolia . Methods A single-masked r and omised controlled trial was initiated in 1999 . 4725 volunteer Mongolian participants ≥50 years old from the capital Ulaanbaatar or the rural province of Bayankhongor were recruited , of which 128 were excluded with glaucoma . 4597 were r and omly allocated to the control , no-screening arm or screening with ultrasound central anterior chamber depth ( cACD ) , with the cut-off set at < 2.53 mm . 685 screen-positive participants were examined and angle closure was identified by gonioscopy in 160 , of which 156 were treated with prophylactic LPI . Primary outcome of incident PACG was determined using both structural and functional evidence from objective grading of paired disc photographs from baseline and follow-up , objective grading of follow-up visual fields and clinical examination . Results Six years later , 801 ( 17.42 % ) participants were known to have died , and a further 2047 ( 53.92 % ) were traced and underwent full ophthalmic examination . In an intention to treat analysis using available data , PACG was diagnosed in 33 participants ( 1.61 % , 95 % CI 1.11 % to 2.25 % ) , of which 19 were in the screened group and 14 in the non-screened group ( OR 1.29 , 95 % CI 0.65 to 2.60 , p=0.47 ) , indicating no difference between groups . Conclusions We were not able to identify a reduction in the 6 year incidence of PACG after screening with cACD < 2.53 mm and prophylactic treatment of PAC PURPOSE To assess the immediate effect of laser peripheral iridotomy ( LPI ) and mechanisms of angle closure in a population -based study of primary angle closure ( PAC ) suspects . DESIGN Prospect i ve interventional study . PARTICIPANTS People identified as PAC suspects aged 50 to 79 years from a population -based survey in Guangzhou , China . INTERVENTION Laser peripheral iridotomy was performed in 1 r and omly selected eye . Examinations were carried out before and 2 weeks after the intervention . MAIN OUTCOME MEASURES Intraocular pressure ( IOP ) , ultrasound biometry , optical pachymetry , and gonioscopy . RESULTS A total of 72 people with bilateral suspected PAC participated in the study . Mean IOP decreased by 3 mmHg ( P<0.001 ) , but axial anterior chamber depth did not change significantly ( P = 0.784 ) after LPI . Median limbal anterior chamber depth increased from 15 % to 25 % of peripheral corneal thickness ( P<0.001 , Wilcoxon signed-rank test ) . Median iridotrabecular angle width increased from 0 degrees to 10 degrees in the superior quadrant and from 10 degrees to 30 degrees in the inferior quadrant ( P<0.001 ) . Nevertheless , 14 eyes ( 19.4 % ) still had 3 or more quadrants in which the posterior ( usually pigmented ) trabecular meshwork could not be seen after laser iridotomy . CONCLUSIONS This study confirms that LPI results in a significant increase in the angle width in Chinese people with narrow angles . However , one fifth of eyes had residual angle closure after LPI . Although this report confirms that iridotomy widens the anterior chamber angle in most PAC suspects , long-term prospect i ve studies with a larger sample size are required to determine if the risks of PAC glaucoma and other related pathologic sequelae are reduced after prophylactic LPI and to investigate the risk-to-benefit ratio before recommending widespread use of prophylactic LPI in this population PURPOSE To evaluate changes in lens opacity in the first year after prophylactic laser peripheral iridotomy ( LPI ) performed in fellow eyes of subjects with acute primary angle closure ( APAC ) . DESIGN Prospect i ve observational case series . PARTICIPANTS Sixty Asian subjects with unilateral APAC . METHODS All fellow eyes underwent prophylactic LPI within the first week of presentation , followed by 1 week of topical steroids . The degree of lens opacity was grade d at the slit-lamp examination using the Lens Opacity Classification System III ( LOCS III ) with st and ard color photographs as the reference for grading of lens opacity . This was performed 2 weeks , 4 months , and 12 months after LPI . Progression in lens opacity was defined as an increase in LOCS III grade by 2 or more units in any lens region . MAIN OUTCOME MEASURES Lens Opacity Classification Sytem III grade s in nuclear , cortical , and posterior subcapsular ( PSC ) regions . RESULTS Most patients were Chinese ( 85 % ) and female ( 63.3 % ) , with an average age of 61.5 + /- 10.6 years . The mean baseline LOCS grade s in the nuclear , cortical , and PSC regions were 3.58 + /- 0.74 , 0.57 + /- 1.08 , and 0.23 + /- 0.72 , respectively . With 12 months of follow-up , 14 of the 60 eyes ( 23.3 % ; 95 % confidence interval , 16.9 - 29.7 % ) showed significant progression in any lens region . Progression in the nuclear , cortical , and PSC regions was documented in 5 % , 6.7 % , and 16.7 % of cases , respectively . By use of logistic regression , the following factors were not found to be significant for cataract progression in any lens region : age , race , gender , history of hypertension or diabetes , presence of peripheral anterior synechiae or angle width at baseline , and total laser energy delivered . CONCLUSIONS In fellow eyes of APAC , prophylactic LPI is complicated by significant cataract progression , mainly in the posterior subcapsular region . These findings may have implication s for the role of prophylactic LPI in the prevention of angle-closure blindness Purpose : To set priorities for new systematic review s ( SRs ) and r and omized clinical trials on the management of primary angle closure ( PAC ) using clinical practice guidelines and a survey of Asia-Pacific clinicians . Methods : We restated the American Academy of Ophthalmology ’s Preferred Practice Patterns recommendations for management of PAC into answerable clinical questions . We asked participants at the Asia-Pacific Joint Glaucoma Congress 2010 in Taipei to rate the importance of having an answer to each question for providing effective patient care , using a Likert-type scale and scoring from 0 ( not important at all ) to 10 ( highly important ) . We identified relevant SRs and mapped the evidence to clinical questions to identify evidence gaps . Results : We generated 42 clinical questions . One hundred seventy-five individuals agreed to participate in the survey , 132 responded ( 75.4 % response rate ) and 96 completed the question naire ( 54.9 % usable response rate ) . Questions rated important include laser iridotomy for the prevention of angle closure in primary angle-closure suspects , further therapies in eyes with plateau iris syndrome after laser iridotomy , and evaluation of the fellow eye in acute angle-closure patients for improving prognosis . Up-to- date and conclusive SR evidence was not available for any of the 42 clinical questions . Conclusions : We identified high priority clinical questions on the management of PAC , none of which had reliable SR evidence available . New SRs and r and omized clinical trials can be initiated to address these evidence gaps Objective To assess the effect of prophylactic laser peripheral iridotomy ( LPI ) on corneal endothelial cell density ( ECD ) and morphology in primary angle closure suspects ( PACS ) over 3 years . Methods In this prospect i ve cohort study , subjects underwent LPI in one eye , while the fellow eye was untreated . Specular microscopy was performed at baseline and after 1 and 3 years . Central corneal ECD and morphology of both eyes were assessed using non-contact specular microscopy ( Konan SP-9000LC , Konan Inc , Hyogo , Japan ) . Results 230 subjects completed 3-year follow-up . The mean age was 62.5±8.0 years , and the majority of subjects were Chinese ( 92.3 % ) and women ( 75.4 % ) . In eyes that underwent LPI , ECD was significantly lower at year 1 ( 2462.3 , 95 % CI 2414.5 to 2510.0 , p<0.0001 ) and year 3 ( 2510.6 , 95 % CI 2462.1 to 2559.2 , p=0.0006 ) compared with baseline ( 2609.1 , 95 % CI 2551.4 to 2666.7 ) . There was also a significant decrease in ECD in fellow untreated eyes from baseline to year 1 ( p<0.0001 ) and year 3 ( p=0.01 ) . The decrease in ECD at 3 years compared with the baseline in treated and untreated eyes was similar ( 2.1 % vs 0.9 % , p=0.20 ) . Conclusions In PACS eyes , there was decrease in ECD in LPI-treated and control eyes over 3 years , with no significant difference between groups PURPOSE To determine the immediate changes in intraocular pressure ( IOP ) after laser peripheral iridotomy in primary angle-closure suspects . DESIGN Prospect i ve , r and omized controlled trial ( split-body design ) . PARTICIPANTS Seven hundred thirty-four Chinese people 50 to 70 years of age . METHODS Primary angle-closure suspects underwent iridotomy using a neodymium : yttrium-aluminum-garnet laser in 1 r and omly selected eye , with the fellow eye serving as a control . Intraocular pressure was measured using Goldmann applanation tonometry before treatment and 1 hour and 2 weeks after treatment . Total energy used and complications were recorded . Risk factors for IOP rise after laser peripheral iridotomy were investigated . MAIN OUTCOME MEASURES Intraocular pressure . RESULTS The proportion of treated eyes with an IOP spike ( an elevation of ≥8 mmHg more than baseline ) at 1 hour and 2 weeks after treatment was 9.8 % ( 95 % confidence interval [ CI ] , 7.7 - 12.0 ) and 0.82 % ( 95 % CI , 0.2 - 1.5 ) , respectively . Only 4 ( 0.54 % ) of 734 eyes ( 95 % CI , 0.01 - 1.08 ) had an immediate posttreatment IOP of 30 mmHg or more and needed medical intervention . The average IOP 1 hour after treatment was 17.5±4.7 mmHg in the treated eyes , as compared with 15.2±2.6 mmHg in controls . At 2 weeks after treatment , these values were 15.6±3.4 mmHg in treated eyes and 15.1±2.7 mmHg in controls ( P<0.001 ) . No significant difference was detected in the baseline IOP of the treated and untreated eyes . Logistic regression showed that the incidence of IOP spike was associated with greater laser energy used and shallower central anterior chamber . CONCLUSIONS Laser peripheral iridotomy in primary angle-closure suspects result ed in significant IOP rise in 9.8 % and 0.82 % of cases at 1 hour and 2 weeks , respectively . Eyes in which more laser energy and a higher number of laser pulses were used and those with shallower central anterior chambers were at increased risk for IOP spikes at 1 hour after laser peripheral iridotomy PURPOSE To quantitate changes in anterior ocular segment anatomy after laser iridotomy for pupillary block angle closure . METHODS We prospect ively performed ultrasound biomicroscopy and A-scan biometry in 13 eyes of 13 consecutive untreated patients with relative pupillary block and appositional angle closure , without peripheral anterior synechiae on indentation gonioscopy . A radial , perpendicular image in the horizontal temporal meridian was obtained with ultrasound biomicroscopy before and one week after laser iridotomy in each eye . RESULTS Mean age of the 13 patients was 69.3 + /- 1.8 ( S.E. ) years , mean refractive error was + 1.37 + /- 0.39 diopters , and mean axial length was 22.54 + /- 0.20 mm . In 13 eyes , before and after laser iridotomy measurements of angle-opening distance ( 0.11 + /- 0.02 vs. 0.18 + /- 0.02 mm ) ( P = .0004 ; paired t test ) , angle aperture ( 8.3 + /- 1.3 vs 18.6 + /- 2.8 degrees ) ( P = .0003 ) and iris-lens contact distance ( 0.58 + /- 0.06 vs 1.18 + /- 0.14 mm ) ( P = .0003 ) were greater postoperatively , but anterior chamber depth was unchanged ( P = .7 ) . CONCLUSIONS Flattening of the iris after laser iridotomy for pupillary block causes an increase in iris-lens contact . The change in angle configuration after iridotomy results more from an alteration in aqueous pressure gradients across the iris rather than from posterior lens movement OBJECTIVE To assess the impact of laser peripheral iridotomy ( LPI ) on forward-scatter of light and subjective visual symptoms and to identify LPI parameters influencing these phenomena . DESIGN Cohort study derived from a r and omized trial , using an external control group . PARTICIPANTS Chinese subjects initially aged 50 or older and 70 years or younger with bilateral narrow angles undergoing LPI in 1 eye selected at r and om , and age- and gender-matched controls . METHODS Eighteen months after laser , LPI-treated subjects underwent digital iris photography and photogrammetry to characterize the size and location of the LPI , Lens Opacity Classification System III cataract grading , and measurement of retinal straylight ( C-Quant ; OCULUS , Wetzlar , Germany ) in the treated and untreated eyes and completed a visual symptoms question naire . Controls answered the question naire and underwent straylight measurement and ( in a r and om one-sixth sample ) cataract grading . MAIN OUTCOME MEASURES Retinal straylight levels and subjective visual symptoms . RESULTS Among 230 LPI-treated subjects ( 121 [ 58.8 % ] with LPI totally covered by the lid , 43 [ 19.8 % ] with LPI partly covered by the lid , 53 [ 24.4 % ] with LPI uncovered by the lid ) , 217 ( 94.3 % ) completed all testing , as did 250 ( 93.3 % ) of 268 controls . Age , gender , and prevalence of visual symptoms did not differ between treated subjects and controls , although nuclear ( P<0.01 ) and cortical ( P = 0.03 ) cataract were less common among controls . Neither presenting visual acuity nor straylight score differed between the treated and untreated eyes among all treated persons , nor among those ( n = 96 ) with LPI partially or totally uncovered . Prevalence of subjective glare did not differ significantly between participants with totally covered LPI ( 6.61 % ; 95 % confidence interval [ CI ] , 3.39%-12.5 % ) , partially covered LPI ( 11.6 % ; 95 % CI , 5.07%-24.5 % ) , or totally uncovered LPI ( 9.43 % ; 95 % CI , 4.10%-10.3 % ) . In regression models , only worse cortical cataract grade ( P = 0.01 ) was associated significantly with straylight score , and no predictors were associated with subjective glare . None of the LPI size or location parameters were associated with straylight or subjective symptoms . CONCLUSIONS These results suggests that LPI is safe regarding measures of straylight and visual symptoms . This r and omized design provides strong evidence that treatment programs for narrow angles would be unlikely to result in important medium-term visual disability PURPOSE To report the progression of ocular hypertension ( OHT ) to primary open angle glaucoma ( POAG ) during a 5-year follow up of a population -based sample . METHODS Twenty-nine patients diagnosed to have OHT and 110 r and omly selected normals from a population -based study in 1995 were invited for ocular examination in 2000 . All patients underwent a complete ophthalmic examination ; including the daytime diurnal variation of intraocular pressure ( IOP ) and measurement of central corneal thickness ( CCT ) . The " corrected " IOP was used for analysis . Progression to POAG was based on typical optic disc changes with corresponding field defects on automated perimetry . RESULTS Twenty-five of the 29 persons with OHT who could be contacted were examined . After correcting for CCT , two persons were reclassified as normal . Four of 23 ( 17.4 % ; 95 % CI : 1.95 - 32.75 ) had progressed to POAG . One person amongst the 110 normals progressed to normal tension glaucoma ( NTG ) . The relative risk of progression amongst OHT was 19.1 ( 95 % CI : 2.2 - 163.4 ) . All those who progressed had bilateral OHT . The mean and peak IOP in those who progressed was 25.4 mm Hg and 29.3 mm Hg compared to 23.9 mm Hg and 25.7 mm Hg in those who did not . Those who progressed had more than 8 mm Hg diurnal variation . The diurnal variation was less than 6 mm Hg in those who did not progress . No patient developed blindness due to glaucoma . CONCLUSION The 5-year incidence of POAG amongst OHT in this population was 17.4 % ( 3.5 % per year ) . Bilateral OHT , higher peak IOP and large diurnal variation may be the risk factors for progression A prospect i ve short-term clinical study evaluated argon and Q-switched neodymium : YAG laser iridotomies in 40 eyes of 20 patients with primary chronic angle-closure glaucoma . All patients had bilateral iridotomies with one eye r and omly assigned to argon laser and the fellow eye to neodymium : YAG laser therapy . In all eyes a patent iridotomy was created in one treatment session . A mean of 12 + /- 11 and 0.033 + /- 0.025 J were needed for iridotomy formation in argon and neodymium : YAG treated eyes respectively . No neodymium : YAG and six ( 30 % ) argon iridotomies had marked closure requiring retreatment . Immediate postoperative intraocular pressure elevation greater than 10 mmHg was seen in seven ( 35 % ) argon and six ( 30 % ) neodymium : YAG-treated eyes . Nine ( 45 % ) eyes treated with the neodymium : YAG laser had bleeding from the iridotomy site . No acute lens damage was found in the neodymium : YAG eyes while seven ( 35 % ) lenses in the argon group had focal opacities . Seven ( 35 % ) neodymium : YAG and five ( 25 % ) argon treated eyes had focal nonprogressive corneal opacities above the iridotomy site . Specular microscopy showed a significant central corneal endothelial loss in argon laser treated eyes . No eyes had detectable retinal damage PURPOSE To determine the incidence and baseline clinical and anterior segment optical coherence tomography ( AS-OCT ) predictors associated with residual angle closure as assessed by gonioscopy 1 year after laser peripheral iridotomy ( LPI ) in primary angle closure suspects ( PACS ) . DESIGN Sub analysis of r and omized controlled trial data . METHODS AS-OCT images from 181 PACS subjects ≥50 years of age were analyzed using customized software before and 1 year after LPI . Other parameters assessed were intraocular pressure ( IOP ) and axial length ( Axl ) . Residual angle closure was defined as the inability to see the posterior trabecular meshwork for at least 2 quadrants on gonioscopy after LPI . Multivariate regression analysis determined the baseline predictors of residual angle closure 1 year after LPI . RESULTS The mean age of participants was 62.4 ( st and ard deviation 9.9 ) years . The majority were female ( 137 , 75.7 % ) and Chinese ( 174 , 96.1 % ) . At 1 year post LPI , 148 ( 81.8 % ) subjects had gonioscopic residual angle closure . Univariate analysis showed that baseline Axl , anterior chamber area , anterior chamber volume , angle opening distance at 750 μm from the scleral spur , and angle recess area were smaller while baseline lens vault and iris curvature were larger in residual angle closure subjects ( all P < .05 ) . Multivariate analysis revealed that baseline iris volume ( B = -0.08 , P = .035 ) and baseline IOP ( B = 0.23 , P = .032 ) were predictors for residual angle closure . CONCLUSIONS One year after LPI , > 80 % of PACS had gonioscopic residual angle closure . Greater baseline iris volume and higher IOP at baseline are independent risk factors for residual gonioscopic angle closure OBJECTIVE To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects ( PACS ) treated by laser peripheral iridotomy ( LPI ) and in untreated fellow eyes . DESIGN Longitudinal cohort study . PARTICIPANTS Primary angle-closure suspects aged 50 to 70 years were enrolled in a r and omized , controlled clinical trial . METHODS Each participant was treated by LPI in 1 r and omly selected eye , with the fellow eye serving as a control . Angle width was assessed in a masked fashion using gonioscopy and anterior segment optical coherence tomography ( AS-OCT ) before and at 2 weeks , 6 months , and 18 months after LPI . MAIN OUTCOME MEASURES Angle width in degrees was calculated from Shaffer grade s assessed under static gonioscopy . Angle configuration was also evaluated using angle opening distance ( AOD250 , AOD500 , AOD750 ) , trabecular-iris space area ( TISA500 , TISA750 ) , and angle recess area ( ARA ) measured in AS-OCT images . RESULTS No significant difference was found in baseline measures of angle configuration between treated and untreated eyes . At 2 weeks after LPI , the drainage angle on gonioscopy widened from a mean of 13.5 ° at baseline to a mean of 25.7 ° in treated eyes , which was also confirmed by significant increases in all AS-OCT angle width measures ( P<0.001 for all variables ) . Between 2 weeks and 18 months after LPI , a significant decrease in angle width was observed over time in treated eyes ( P<0.001 for all variables ) , although the change over the first 5.5 months was not statistically significant for angle width measured under gonioscopy ( P = 0.18 ) , AOD250 ( P = 0.167 ) and ARA ( P = 0.83 ) . In untreated eyes , angle width consistently decreased across all follow-up visits after LPI , with a more rapid longitudinal decrease compared with treated eyes ( P values for all variables ≤0.003 ) . The annual rate of change in angle width was equivalent to 1.2 ° /year ( 95 % confidence interval [ CI ] , 0.8 - 1.6 ) in treated eyes and 1.6 ° /year ( 95 % CI , 1.3 - 2.0 ) in untreated eyes ( P<0.001 ) . CONCLUSIONS Angle width of treated eyes increased markedly after LPI , remained stable for 6 months , and then decreased significantly by 18 months after LPI . Untreated eyes experienced a more consistent and rapid decrease in angle width over the same time period |
2,113 | 30,624,991 | This systematic review and meta- analysis demonstrates a clinical ly meaningful association between objective ly monitored steps per day and PWv , an accepted indicator of arterial stiffness and an early sub clinical risk factor for cardiovascular disease . | Arterial stiffness has emerged as an independent predictor of cardiovascular morbidity and mortality .
Furthermore , objective ly monitored steps per day is widely perceived to be beneficial for controlling health risk factors , and for preventing morbidity and mortality .
The aim of this review was to determine the relationship between steps per day and arterial stiffness , as measured by its reference st and ard , pulse wave velocity ( PWv ) . | Background Age‐related endothelial dysfunction and vascular stiffening are associated with increased cardiovascular ( CV ) risk . Many groups have encouraged goals of ≥10 000 steps/day or ≥30 min/day of moderate intensity physical activity ( MPA ) to reduce age‐related CV risk . The impact of MPA on the vasculature of older adults remains unclear . Methods and Results We r and omized 114 sedentary older adults ages ≥50 to 12 weeks of either no intervention ( group 1 ) , a pedometer‐only intervention ( group 2 ) , or a pedometer with an interactive website employing strategies to increase the adoption of habitual physical activity ( PA , group 3 ) . Endothelial function by brachial flow‐mediated dilation ( FMD% ) , vascular stiffness by tonometry , step‐count by pedometer , and PA intensity/distribution by accelerometer were measured . Step‐count increased in groups 2 ( 5136±1554 to 9596±3907 , P<0.001 ) and 3 ( 5474±1512 to 8167±3111 , P<0.001 ) but not in group 1 ( 4931±1667 to 5410±2410 ) . Both groups 2 and 3 increased MPA ≥30 min/day . Only group 3 increased MPA in continuous bouts of ≥10 minutes ( P<0.001 ) and improved FMD% ( P=0.001 ) . Neither achievement of ≥10 000 steps/day nor ≥30 min/day of MPA result ed in improved FMD% . However , achieving ≥20 min/day in MPA bouts result ed in improved FMD% . No changes in vascular stiffness were observed . Conclusions MPA reverses age‐related endothelial dysfunction , but may require MPA to be performed in bouts of ≥10 minutes duration for ≥20 min/day to be effective . Commonly encouraged PA goals do not guarantee improved endothelial function and may not be as effective in reducing CV risk . Clinical Trial Registration URL : Clinical trials.gov . Unique identifier : NCT‐01212978 Background Self – reported physical activity has been inversely associated with mortality but the effect of objective ly measured step activity on mortality has never been evaluated . The objective is to determine the prospect i ve association of daily step activity on mortality among free-living adults . Methods and Findings Cohort study of free-living adults residing in Tasmania , Australia between 2000 and 2005 who participated in one of three cohort studies ( n = 2 576 total participants ) . Daily step activity by pedometer at baseline at a mean of 58.8 years of age , and for a subset , repeated monitoring was available 3.7 ( SD 1.3 ) years later ( n = 1 679 ) . All-cause mortality ( n = 219 deaths ) was ascertained by record-linkage to the Australian National Death Index ; 90 % of participants were followed-up over ten years , until June 2011 . Higher daily step count at baseline was linearly associated with lower all-cause mortality ( adjusted hazard ratio AHR , 0.94 ; 95 % CI , 0.90 to 0.98 per 1 000 steps ; P = 0.004 ) . Risk was altered little by removing deaths occurring in the first two years . Increasing baseline daily steps from sedentary to 10 000 steps a day was associated with a 46 % ( 95 % CI , 18 % to 65 % ; P = 0.004 ) lower risk of mortality in the decade of follow-up . In addition , those who increased their daily steps over the monitoring period had a substantial reduction in mortality risk , after adjusting for baseline daily step count ( AHR , 0.39 ; 95 % CI , 0.22 to 0.72 ; P = 0.002 ) , or other factors ( AHR , 0.38 ; 95 % CI , 0.21–0.70 ; P = 0.002 ) . Conclusions Higher daily step count was linearly associated with subsequent long term mortality among free living adults . These data are the first to quantify mortality reductions using an objective measure of physical activity in a free living population . They strongly underscore the importance of physical inactivity as a major public health problem Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Being overweight is associated with vascular abnormalities , which are important in the development of atherosclerosis . However , little is known about dietary and lifestyle determinants of vascular function in overweight children . In adults , dietary protein and milk intake are associated with reduced blood pressure and reduced risk of metabolic syndrome . This study examined the associations between dietary protein , milk intake , physical activity , and adiposity on arterial stiffness in overweight children . In a cross-sectional study , overweight children with habitual milk intakes ≤ 250 mL/d were examined by DXA scans , pedometer counts , anthropometry , and metabolic variables . Dietary intake was registered for 4 d. The outcomes were arterial stiffness measured by pulse wave velocity ( PWV ) ( n = 182 ) and augmentation index ( Aix ) ( n = 183 ) . The PWV ( mean ± SD ) was 4.78 ± 0.72 m/s and the Aix was -0.77 ± 9.44 % . In multivariate models , the and roid fat : gynoid fat and and roid fat : body fat ratios were positively associated with PWV ( β = 1.49 and β = 10.3 , both P < 0.05 ) and Aix ( β = 28.3 , P < 0.01 and β = 153 , P < 0.05 ) , whereas the gynoid fat : body fat ratio was negatively associated with the Aix ( β = -134 ; P < 0.001 ) . Protein intake ( percentage energy ) was positively associated with PWV ( β = 0.05 ; P < 0.01 ) . Milk intake ( L/d ) tended to be negatively associated with PWV ( β = -0.64 ; P = 0.05 ) . Pedometer counts were negatively associated with the Aix ; however , the association became nonsignificant after controlling for HOMA , which was positively associated with the Aix ( β = 0.95 ; P < 0.01 ) . In conclusion , central adiposity and protein intake are associated with increased arterial stiffness measured as PWV in overweight children independent of blood pressure and heart rate . The effect of protein intake may be caused by meat , because the milk intake was low Background New technologies could facilitate changes in lifestyle and improve public health . However , no large r and omized , controlled studies providing scientific evidence of the benefits of their use have been made . The aims of this study are to develop and vali date a smartphone application , and to evaluate the effect of adding this tool to a st and ardized intervention design ed to improve adherence to the Mediterranean diet and to physical activity . An evaluation is also made of the effect of modifying habits upon vascular structure and function , and therefore on arterial aging . Methods / Design A r and omized , double-blind , multicenter , parallel group clinical trial will be carried out . A total of 1215 subjects under 70 years of age from the EVIDENT trial will be included . Counseling common to both groups ( control and intervention ) will be provided on adaptation to the Mediterranean diet and on physical activity . The intervention group moreover will receive training on the use of a smartphone application design ed to promote a healthy diet and increased physical activity , and will use the application for three months . The main study endpoints will be the changes in physical activity , assessed by accelerometer and the 7-day Physical Activity Recall ( PAR ) interview , and adaptation to the Mediterranean diet , as evaluated by an adherence question naire and a food frequency question naire ( FFQ ) . Evaluation also will be made of vascular structure and function based on central arterial pressure , the radial augmentation index , pulse velocity , the cardio-ankle vascular index , and carotid intima-media thickness . Discussion Confirmation that the new technologies are useful for promoting healthier lifestyles and that their effects are beneficial in terms of arterial aging will have important clinical implication s , and may contribute to generalize their application in favor of improved population health . Trial registration Clinical Trials.gov Identifier : CONTEXT Persuasive evidence has demonstrated that increased physical activity is associated with substantial reduction in risk of coronary heart disease . However , the role of physical activity in the prevention of stroke is less well established . OBJECTIVE To examine the association between physical activity and risk of total stroke and stroke subtypes in women . DESIGN AND SETTING The Nurses ' Health Study , a prospect i ve cohort study of subjects residing in 11 US states . SUBJECTS A total of 72,488 female nurses aged 40 to 65 years who did not have diagnosed cardiovascular disease or cancer at baseline in 1986 and who completed detailed physical activity question naires in 1986 , 1988 , and 1992 . MAIN OUTCOME MEASURE Incident stroke occurring between baseline and June 1 , 1994 , compared among quintiles of physical activity level as measured by metabolic equivalent tasks ( METs ) in hours per week . RESULTS During 8 years ( 560,087 person-years ) of follow-up , we documented 407 incident cases of stroke ( 258 ischemic strokes , 67 subarachnoid hemorrhages , 42 intracerebral hemorrhages , and 40 strokes of unknown type ) . In multivariate analyses controlling for age , body mass index , history of hypertension , and other covariates , increasing physical activity was strongly inversely associated with risk of total stroke . Relative risks ( RRs ) in the lowest to highest MET quintiles were 1 . 00 , 0.98 , 0.82 , 0.74 , and 0.66 ( P for trend=.005 ) . The inverse gradient was seen primarily for ischemic stroke ( RRs across increasing MET quintiles , 1.00 , 0.87 , 0.83 , 0.76 , and 0.52 ; P for trend=.003 ) . Physical activity was not significantly associated with subarachnoid hemorrhage or intracerebral hemorrhage . After multivariate adjustment , walking was associated with reduced risk of total stroke ( RRs across increasing walking MET quintiles , 1.00 , 0 . 76 , 0.78 , 0.70 , and 0.66 ; P for trend=.01 ) and ischemic stroke ( RRs across increasing walking MET quintiles , 1.00 , 0.77 , 0.75 , 0.69 , and 0.60 ; P for trend=.02 ) . Brisk or striding walking pace was associated with lower risk of total and ischemic stroke compared with average or casual pace . CONCLUSION These data indicate that physical activity , including moderate-intensity exercise such as walking , is associated with substantial reduction in risk of total and ischemic stroke in a dose-response manner . JAMA . 2000 Background : Physical activity ( PA ) is inversely associated with obesity but the effect has been difficult to quantify using question naires . In particular , the shape of the association has not yet been well described . Pedometers provide an opportunity to better characterize the association . Methods : Residents of households over the age of 25 years in r and omly selected census districts in Tasmania were eligible to participate in the AusDiab cross-sectional survey conducted in 1999–2000 . 1848 completed the AusDiab survey and 1126 of these ( 609 women and 517 men ) wore a pedometer for 2-weekdays . Question naire data on recent PA , TV time and other factors were obtained . The outcomes were waist circumference ( in cm ) and body mass index ( BMI ) ( kg/m2 ) . Results : Increasing daily steps were associated with a decline in the obesity measures . The logarithmic nature of the associations was indicated by a sharper decline for those with lower daily steps . For example , an additional 2000 steps for those taking only 2000 steps per day was associated with a reduction of 2.8 ( 95 % confidence interval ( CI ) : 2.1,4.4 ) cm in waist circumference among men ( for women ; 2.2 ( 95 % CI : 0.6 , 3.9 cm ) ) with a baseline of only 2000 , steps compared to a 0.7 ( 95 % CI 0.3 , 1.1 ) cm reduction ( for women ; 0.6 ( 95 % CI : 0.2 , 1.0 ) ) for those already walking 10 000 steps daily . In the multivariable analysis , clearer associations were detected for PA and these obesity measures using daily step number rather than PA time by question naire . Interpretation : Pedometer measures of activity indicate that the inverse association between recent PA and obesity is logarithmic in form with the greatest impact for a given arithmetic step number increase seen at lower levels of baseline activity . The findings from this study need to be examined in prospect i ve setting The central arteries stiffen with age , causing hemodynamic alterations that have been associated with cardiovascular events . Changes in body fat with age may be related to aortic stiffening . The association between vascular stiffness and body fat was evaluated in 2488 older adults ( mean age , 74 years ; 52 % female ; 40 % black ) enrolled in the Study of Health , Aging , and Body Composition ( Health ABC ) , a prospect i ve study of changes in weight and body composition . Clinical sites were located in Pittsburgh , Pa , and Memphis , Tenn. Aortic pulse wave velocity was used as an indirect measure of aortic stiffness . A faster pulse wave velocity indicates a stiffer aorta . Body fat measures were evaluated with dual energy x-ray absorptiometry and computed tomography . Independent of age and blood pressure , pulse wave velocity was positively associated with weight , abdominal circumference , abdominal subcutaneous fat , abdominal visceral fat , thigh fat area , and total fat ( P < 0.001 for all ) . The strongest association was with abdominal visceral fat . Elevated pulse wave velocity was also positively associated with history of diabetes and higher levels of glucose , insulin , and hemoglobin A1c ( P < 0.001 for all ) . In multivariate analysis , independent positive associations with pulse wave velocity were found for age , systolic blood pressure , heart rate , abdominal visceral fat , smoking , hemoglobin A1c , and history of hypertension . The association between pulse wave velocity and abdominal visceral fat was consistent across tertiles of body weight . Among older adults , higher levels of visceral fat are associated with greater aortic stiffness as measured by pulse wave velocity Aims There are few proven strategies to enhance physical activity and cardiometabolic profiles in patients with type 2 diabetes and hypertension . We examined the effects of physician‐delivered step count prescriptions and monitoring . Methods Participants r and omized to the active arm were provided with pedometers and they recorded step counts . Over a 1‐year period , their physicians review ed their records and provided a written step count prescription at each clinic visit . The overall goal was a 3000 steps/day increase over 1 year ( individualized rate of increase ) . Control arm participants were advised to engage in physical activity 30 to 60 min/day . We evaluated effects on step counts , carotid femoral pulse wave velocity ( cfPWV , primary ) and other cardiometabolic indicators including haemoglobin A1c in diabetes ( henceforth abbreviated as A1c ) and Homeostasis Model Assessment ‐Insulin Resistance ( HOMA‐IR ) in participants not receiving insulin therapy . Results A total of 79 % completed final evaluations ( 275/347 ; mean age , 60 years ; SD , 11 ) . Over 66 % of participants had type 2 diabetes and over 90 % had hypertension . There was a net 20 % increase in steps/day in active vs control arm participants ( 1190 ; 95 % CI , 550‐1840 ) . Changes in cfPWV were inconclusive ; active vs control arm participants with type 2 diabetes experienced a decrease in A1c ( −0.38 % ; 95 % CI , −0.69 to −0.06 ) . HOMA‐IR also declined in the active arm vs the control arm ( ie , assessed in all participants not treated with insulin ; −0.96 ; 95 % CI , −1.72 to −0.21 ) . Conclusions A simple physician‐delivered step count prescription strategy incorporated into routine clinical practice led to a net 20 % increase in step counts ; however , this was below the 3000 steps/day targeted increment . While conclusive effects on cfPWV were not observed , there were improvements in both A1c and insulin sensitivity . Future studies will evaluate an amplified intervention to increase impact AIM To explore prospect ively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes . METHODS We analysed data from 135 men and 53 women with Type 2 diabetes , aged 54 - 66 years . Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups : < 5000 steps/day , 5000 - 7499 steps/day , 7500 - 9999 steps/day and ≥10 000 steps/day . Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years . RESULTS The mean ( ±sd ; range ) number of steps/day was 8022 ( ±3765 ; 956 - 20 921 ) . The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest . When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex , age , diabetes duration , HbA1c , BMI , systolic blood pressure , pulse wave velocity at baseline , β-blocker use , statin use , unemployment , smoking and diabetes medication , the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity ( P=0.005 ) . Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s . CONCLUSIONS We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes BACKGROUND The extent to which change in physical activity can modify the risk of cardiovascular disease in individuals at high cardiovascular risk is uncertain . We investigated whether baseline and change in objective ly-assessed ambulatory activity is associated with the risk of a cardiovascular event in individuals at high cardiovascular risk with impaired glucose tolerance . METHODS We assessed prospect i ve data from the NAVIGATOR trial involving 9306 individuals with impaired glucose tolerance who were recruited in 40 countries between January , 2002 , and January , 2004 . Participants also either had existing cardiovascular disease ( if age ≥50 years ) or at least one additional cardiovascular risk factor ( if age ≥55 years ) . Participants were followed-up for cardiovascular events ( defined as cardiovascular mortality , non-fatal stroke , or myocardial infa rct ion ) for 6 years on average and had ambulatory activity assessed by pedometer at baseline and 12 months . Adjusted Cox proportional hazard models quantified the association of baseline and change in ambulatory activity ( from baseline to 12 months ) with the risk of a subsequent cardiovascular event , after adjustment for each other and potential confounding variables . This study is registered with Clinical Trials.govNCT00097786 . FINDINGS During 45,211 person-years follow-up , 531 cardiovascular events occurred . Baseline ambulatory activity ( hazard ratio [ HR ] per 2000 steps per day 0·90 , 95 % CI 0·84 - 0·96 ) and change in ambulatory activity ( 0·92 , 0·86 - 0·99 ) were inversely associated with the risk of a cardiovascular event . Results for change in ambulatory activity were unaffected when also adjusted for changes in body-mass index and other potential confounding variables at 12 months . INTERPRETATION In individuals at high cardiovascular risk with impaired glucose tolerance , both baseline levels of daily ambulatory activity and change in ambulatory activity display a grade d inverse association with the subsequent risk of a cardiovascular event . FUNDING Novartis Pharmaceuticals Objective To determine the relationships between pulse wave velocity ( PWV ) , an estimate of arterial distensibility and cardiovascular risk factors . Design This cross-sectional population -based study was carried out from 1995 to 1997 to investigate these relationships . Population and methods Some 993 subjects , aged 35–64 years ( 52.7 % men ) , living in the south-west of France , were r and omly selected from electoral rolls and participated in a cross-sectional study . Medical examinations were performed by specially trained medical staff . Carotid-femoral PWV was measured using a semi-automatic device ( Complior , Garges les Gonesse , France ) . The relationships between PWV and risk factors were assessed , first in subjects not treated with hypolipidaemic , antidiabetic and antihypertensive drugs and then in treated subjects . In subjects not treated for cardiovascular risk factors , age , gender , systolic blood pressure ( SBP ) and heart rate ( P < 0.001 ) were the variables significantly associated with PWV . In treated patients , age ( P < 0.01 ) , SBP ( P < 0.001 ) , heart rate ( P < 0.001 ) , apolipoprotein B ( P < 0.05 ) and the number of treated cardiovascular risk factors ( P < 0.05 ) were positively correlated with PWV . Conclusion This study shows that , in a sample of subjects at high risk , the cumulative influence of risk factors , even treated , is an independent determinant of arterial stiffness . These results suggest that PWV may be used as a relevant tool to assess the influence of cardiovascular risk factors on aortic stiffness in high-risk patients BACKGROUND Carotid-femoral pulse wave velocity ( PWV ) , as a parameter of aortic stiffness , is an established marker of cardiovascular risk . There has been increasing use of arterial stiffness parameters combining aortic and muscular stiffness or a parameter derived from PWV - the stiffness index beta ( BETA = ln(systolic/diastolic pressure ) × 2 blood viscosity/pulse pressure × PWV(2 ) ) . The aim of this study was to compare different arterial stiffness parameters in a general population r and om sample . METHODS AND RESULTS In 809 individuals from the Czech post-MONICA study ( aged 54 ± 13.5 years , 47 % men ) , we compared the association of carotid-femoral PWV ( cfPWV ) , carotid-ankle PWV ( caPWV ) , and BETA with cardiovascular risk factors , parameters of sub clinical organ damage , and presence of manifest cardiovascular disease . Both cfPWV and caPWV were similarly associated with blood pressure and glucose level , while cfPWV was more strongly associated with age , cholesterol level and glomerular filtration rate whereas caPWV with Sokolow-Lyon index . BETA derived from cfPWV and caPWV was less dependent on blood pressure , while it showed a closer association with coronary heart disease presence , as compared to cfPWV and caPWV . CONCLUSIONS Addition of lower extremity to aortic stiffness has an effect on the association with cardiovascular risk factors while having no effect on the association with manifest cardiovascular disease . Beta transformation of PWV decreases its dependence on blood pressure and may increase its power in cardiovascular risk prediction |
2,114 | 30,796,634 | Qualitative synthesis showed that other motor functions were not improved , while respiratory function test results were contradictory .
Moreover , most of the included studies reported no serious AEs related to VPA use , although weight gain , gastrointestinal symptoms and respiratory symptoms were notable problems .
Conclusions Our study suggests that VPA treatment results in an improvement in gross motor functions for SMA patients , but not in other assessment s of motor function or , possibly , in respiratory function .
Furthermore , VPA appears to be a relatively safe drug , although treatment may be associated with a wide range of AEs ( including body weight increase , fatigue , fever , flu-like symptoms , irritability , and pain ) . | Background Spinal muscular atrophy ( SMA ) is a neuromuscular disorder classified into four types based on the age of onset of the disease .
Early onset is correlated with a higher mortality rate , mainly due to respiratory complications .
Valproic acid ( VPA ) is a histone deacetylase ( HDAC ) inhibitor that has shown positive results on SMA both in experimental and cohort studies .
Objectives This systematic review and meta- analysis aim ed to investigate the efficacy and safety of VPA in patients with SMA . | INTRODUCTION The aim of this study was to determine the safety and therapeutic potential of L-carnitine and valproic acid ( VPA ) in infants with spinal muscular atrophy ( SMA ) . METHODS Our investigation was an open-label phase 2 multicenter trial of L-carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated , matched cohort . Primary outcomes were : safety and adverse events ; secondary outcomes were survival , time to death/>16 hours/day of ventilator support ; motor outcomes ; and maximum ulnar compound motor action potential amplitude . RESULTS A total of 245 AEs were observed in 35 of the 37 treated subjects ( 95 % ) . Respiratory events accounted for 49 % of all adverse events , result ing in 14 deaths . Survival was not significantly different between treated and untreated cohorts . DISCUSSION This trial provides evidence that , in infants with SMA type I , L-carnitine/VPA is ineffective at altering survival . The substantial proportion of infants reaching end-points within 6 months of enrollment underscores the urgent need for pre-symptomatic treatment in SMA type I. Muscle Nerve 57 : 193 - 199 , 2018 Background Valproic acid ( VPA ) has demonstrated potential as a therapeutic c and i date for spinal muscular atrophy ( SMA ) in vitro and in vivo . Methods Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL , a non-ambulatory group of “ sitters ” ( cohort 1 ) and an ambulatory group of “ walkers ” ( cohort 2 ) . Here , we present results for cohort 1 : a multicenter phase II r and omized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2–8 years of age . Sixty-one subjects were r and omized 1∶1 to placebo or treatment for the first six months ; all received active treatment the subsequent six months . The primary outcome was change in the modified Hammersmith Functional Motor Scale ( MHFMS ) score following six months of treatment . Secondary outcomes included safety and adverse event data , and change in MHFMS score for twelve versus six months of active treatment , body composition , quantitative SMN mRNA levels , maximum ulnar CMAP amplitudes , myometry and PFT measures . Results At 6 months , there was no difference in change from the baseline MHFMS score between treatment and placebo groups ( difference = 0.643 , 95 % CI = −1.22–2.51 ) . Adverse events occurred in > 80 % of subjects and were more common in the treatment group . Excessive weight gain was the most frequent drug-related adverse event , and increased fat mass was negatively related to change in MHFMS values ( p = 0.0409 ) . Post-hoc analysis found that children ages two to three years that received 12 months treatment , when adjusted for baseline weight , had significantly improved MHFMS scores ( p = 0.03 ) compared to those who received placebo the first six months . A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores ( p = 0.007 ) . Conclusions This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA . Weight gain , age and treatment duration were significant confounding variables that should be considered in the design of future trials . Trial Registry Clinical trials.gov Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Spinal muscular atrophy ( SMA ) is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn , result ing in hypotonia and muscle weakness . The disease is caused by deletion or mutation in the telomeric copy of SMN gene ( SMN1 ) and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene ( SMN2 ) . The SMN2 mRNA lacks exon 7 , result ing in a production of lower amounts of the full-length SMN protein . Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene . One of these drugs is the valproic acid ( VPA ) , a histone deacetylase inhibitor . Methods Twenty-two patients with type II and III SMA , aged between 2 and 18 years , were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test ( Medical Research Council scale-MRC ) , the Hammersmith Functional Motor Scale ( HFMS ) , and the Barthel Index . Results After 12 months of therapy , the patients did not gain muscle strength . The group of children with SMA type II presented a significant gain in HFMS scores during the treatment . This improvement was not observed in the group of type III patients . The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result . There was an improvement of the daily activities at the end of the VPA treatment period . Conclusion Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease . Trial Registration Clinical Trials.gov : Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background Multiple lines of evidence have suggested that valproic acid ( VPA ) might benefit patients with spinal muscular atrophy ( SMA ) . The SMA CARNIVAL TRIAL was a two part prospect i ve trial to evaluate oral VPA and l-carnitine in SMA children . Part 1 targeted non-ambulatory children ages 2–8 in a 12 month cross over design . We report here Part 2 , a twelve month prospect i ve , open-label trial of VPA and L-carnitine in ambulatory SMA children . Methods This study involved 33 genetically proven type 3 SMA subjects ages 3–17 years . Subjects underwent two baseline assessment s over 4–6 weeks and then were placed on VPA and L-carnitine for 12 months . Assessment s were performed at baseline , 3 , 6 and 12 months . Primary outcomes included safety , adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend ( MHFMS-Extend ) , timed motor tests and fine motor modules . Secondary outcomes included changes in ulnar compound muscle action potential amplitudes ( CMAP ) , h and held dynamometry , pulmonary function , and Pediatric Quality of Life Inventory scores . Results Twenty-eight subjects completed the study . VPA and carnitine were generally well tolerated . Although adverse events occurred in 85 % of subjects , they were usually mild and transient . Weight gain of 20 % above body weight occurred in 17 % of subjects . There was no significant change in any primary outcome at six or 12 months . Some pulmonary function measures showed improvement at one year as expected with normal growth . CMAP significantly improved suggesting a modest biologic effect not clinical ly meaningful . Conclusions This study , coupled with the CARNIVAL Part 1 study , indicate that VPA is not effective in improving strength or function in SMA children . The outcomes used in this study are feasible and reliable , and can be employed in future trials in SMA . Trial Regsitration Clinical trials.gov Preliminary in vitro and in vivo studies with valproic acid ( VPA ) in cell lines and patients with spinal muscular atrophy ( SMA ) demonstrate increased expression of SMN , supporting the possibility of therapeutic benefit . We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials . Subjects included 2 SMA type I ages 2–3 years , 29 SMA type II ages 2–14 years and 11 type III ages 2–31 years , recruited from a natural history study . VPA was well-tolerated and without evident hepatotoxicity . Carnitine depletion was frequent and temporally associated with increased weakness in two subjects . Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale ( MHFMS ) , electrophysiologic measures of innervation including maximum ulnar compound muscle action potential ( CMAP ) amplitudes and motor unit number estimation ( MUNE ) , body composition and bone density via dual-energy X-ray absorptiometry ( DEXA ) , and quantitative blood SMN mRNA levels . Clear decline in motor function occurred in several subjects in association with weight gain ; mean fat mass increased without a corresponding increase in lean mass . We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II ( p≤0.001 ) ; however , significant improvement was almost entirely restricted to participants < 5 years of age . Full length SMN levels were unchanged and Δ7SMN levels were significantly reduced for 2 of 3 treatment visits . In contrast , bone mineral density ( p≤0.0036 ) and maximum ulnar CMAP scores ( p≤0.0001 ) increased significantly . Conclusions While VPA appears safe and well-tolerated in this initial pilot trial , these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials . This study highlights potential strengths and limitations of various c and i date outcome measures and underscores the need for additional controlled clinical trials with VPA targeting more restricted cohorts of subjects . Trial Registration Clinical Abstract Background : Clinical trials of therapies for spinal muscular atrophy ( SMA ) that are design ed to increase the expression the SMN protein ideally include careful assessment of relevant SMN biomarkers . Objective : In the SMA VALIANT trial , a recent double-blind placebo-controlled crossover study of valproic acid ( VPA ) in ambulatory adult subjects with SMA , we investigated relevant pharmacodynamic biomarkers in blood sample s from SMA subjects by direct longitudinal measurement of histone acetylation and SMN mRNA and protein levels in the presence and absence of VPA treatment . Methods : Thirty-three subjects were r and omized to either VPA or placebo for the first 6 months followed by crossover to the opposite arm for an additional 6 months . Outcome measures were compared between the two treatments ( VPA and placebo ) using a st and ard crossover analysis . Results : A significant increase in histone H4 acetylation was observed with VPA treatment ( p = 0.005 ) . There was insufficient evidence to suggest a treatment effect with either full length or truncated SMN mRNA transcript levels or SMN protein levels . Conclusions : These measures were consistent with the observed lack of change in the primary clinical outcome measure in the VALIANT trial . These results also highlight the added benefit of molecular and pharmacodynamic biomarker measurements in the interpretation of clinical trial outcomes INTRODUCTION An open-label trial suggested that valproic acid ( VPA ) improved strength in adults with spinal muscular atrophy ( SMA ) . We report a 12-month , double-blind , cross-over study of VPA in ambulatory SMA adults . METHODS There were 33 subjects , aged 20–55 years , included in this investigation . After baseline assessment , subjects were r and omized to receive VPA ( 10–20 mg/kg/day ) or placebo . At 6 months , patients were switched to the other group . Assessment s were performed at 3 , 6 , and 12 months . The primary outcome was the 6-month change in maximum voluntary isometric contraction testing with pulmonary , electrophysiological , and functional secondary outcomes . RESULTS Thirty subjects completed the study . VPA was well tolerated , and compliance was good . There was no change in primary or secondary outcomes at 6 or 12 months . CONCLUSIONS VPA did not improve strength or function in SMA adults . The outcomes used are feasible and reliable and can be employed in future trials in SMA adults Spinal muscular atrophy results from loss of the survival motor neuron 1 ( SMN1 ) gene and malfunction of the remaining SMN2 . We investigated whether valproic acid can elevate human SMN expression in vivo BACKGROUND Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy . Nusinersen is specifically design ed to alter splicing of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron ( SMN ) protein that is deficient in patients with spinal muscular atrophy . METHODS This open-label , phase 2 , escalating dose clinical study assessed the safety and tolerability , pharmacokinetics , and clinical efficacy of multiple intrathecal doses of nusinersen ( 6 mg and 12 mg dose equivalents ) in patients with infantile-onset spinal muscular atrophy . Eligible participants were of either gender aged between 3 weeks and 7 months old with onset of spinal muscular atrophy symptoms between 3 weeks and 6 months , who had SMN1 homozygous gene deletion or mutation . Safety assessment s included adverse events , physical and neurological examinations , vital signs , clinical laboratory tests , cerebrospinal fluid laboratory tests , and electrocardiographs . Clinical efficacy assessment s included event free survival , and change from baseline of two assessment s of motor function : the motor milestones portion of the Hammersmith Infant Neurological Exam-Part 2 ( HINE-2 ) and the Children 's Hospital of Philadelphia Infant Test of Neuromuscular Disorders ( CHOP-INTEND ) motor function test , and compound motor action potentials . Autopsy tissue was analysed for target engagement , drug concentrations , and pharmacological activity . HINE-2 , CHOP-INTEND , and compound motor action potential were compared between baseline and last visit using the Wilcoxon signed-rank test . Age at death or permanent ventilation was compared with natural history using the log-rank test . The study is registered at Clinical Trials.gov , number NCT01839656 . FINDINGS 20 participants were enrolled between May 3 , 2013 , and July 9 , 2014 , and assessed through to an interim analysis done on Jan 26 , 2016 . All participants experienced adverse events , with 77 serious adverse events reported in 16 participants , all considered by study investigators not related or unlikely related to the study drug . In the 12 mg dose group , incremental achievements of motor milestones ( p<0·0001 ) , improvements in CHOP-INTEND motor function scores ( p=0·0013 ) , and increased compound muscle action potential amplitude of the ulnar nerve ( p=0·0103 ) and peroneal nerve ( p<0·0001 ) , compared with baseline , were observed . Median age at death or permanent ventilation was not reached and the Kaplan-Meier survival curve diverged from a published natural history case series ( p=0·0014 ) . Analysis of autopsy tissue from patients exposed to nusinersen showed drug uptake into motor neurons throughout the spinal cord and neurons and other cell types in the brainstem and other brain regions , exposure at therapeutic concentrations , and increased SMN2 mRNA exon 7 inclusion and SMN protein concentrations in the spinal cord . INTERPRETATION Administration of multiple intrathecal doses of nusinersen showed acceptable safety and tolerability , pharmacology consistent with its intended mechanism of action , and encouraging clinical efficacy . Results informed the design of an ongoing , sham-controlled , phase 3 clinical study of nusinersen in infantile-onset spinal muscular atrophy . FUNDING Ionis Pharmaceuticals , Inc and Biogen |
2,115 | 30,942,298 | CONCLUSION Reminiscence Therapy has potential efficacy for maintaining cognition and decrease of depressive symptomatology in the target population | OBJECTIVE To identify the best available evidence on the efficacy of Reminiscence Therapy in cognition , depressive symptoms and quality of life in elderly individuals with cognitive impairment . | BACKGROUND This study examines the effectiveness of a nursing home staff training program design ed to improve the interaction between residents with dementia and their caregivers . METHODS A three-arm cluster-r and omized and controlled population of 96 caregivers and 210 residents was used . Caregivers of the intervention group ( IG ) received a three-month training program in dementia care . Data were gathered at baseline , immediately after the training and at a six-month follow-up- assessment . Short- and long-term effects of the training program were assessed in comparison with another intervention referred to as the relaxation group ( RG ) and a wait-list control group ( CG ) . RESULTS Results indicated significant positive effects of the training program on caregivers ' knowledge immediately after the training and on the use of physical restraints at the six-month follow-up . Caregivers ' overall competence increased significantly both in the IG and in the RG . No intervention effects were found on caregivers ' level of burnout , their health complaints or on the use of sedative drugs . Relaxation training was more successful in the reduction of caregivers ' health complaints . CONCLUSIONS Results of the study indicate both the effectiveness and the limitations of a general training program in dementia care . The complexity of the nursing home setting potentially needs more complex interventions . Ongoing and continued support of the caregivers , as well as changes in organization and environment , are more likely to be helpful in the long-term improvement in the quality of care . Future research should focus on studies of specific interventions , such as the interesting effects of relaxation training on the caregivers ' state of health WHAT IS KNOWN ON THE SUBJECT ? : To stimulate reminiscence of older adults with dementia performed individually or through group sessions is a well-known practice in nursing homes result ing in effects on behaviour and well-being as an alternative for medication . Robust scientific proof of the effectiveness of individual reminiscence therapy performed in nursing homes is sparse . WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE ? : We have provided individual st and ardized reminiscence therapy to residents with dementia . The therapy was developed and tested in a previous study and performed in this study by trained nursing home volunteers . In comparison with a control group who received usual care , residents who received the reminiscence therapy showed significant less depressive symptoms . Moreover , residents were , in general , attentive , open and collaborative during the sessions and volunteers experienced the sessions as useful and pleasant . WHAT ARE THE IMPLICATION S FOR PRACTICE ? : Individual reminiscence therapy can be learned and used by nursing home volunteers to improve care in nursing homes . ABSTRACT Aim To investigate the effect of a st and ardized individualized intervention based on the SolCos transformational reminiscence model on depressive symptoms ( primary outcome ) , cognition and behaviour ( secondary outcomes ) for older people with mild to moderate dementia , performed by trained nursing home volunteers as facilitators . Background Because of limited pharmacological treatment options for older adults with dementia relevant physical , sensory , psychological or social interventions offer alternative opportunities . Method R and omized controlled trial ( IS RCT N74355073 ) was set up in two nursing homes with 29 and 31 residents in the intervention and the control groups respectively . Eighteen nursing home volunteers were trained to perform the reminiscence therapy . Various assessment scales were measured pre- and post-sessions . Results Linear regression analysis showed an impact on depressive symptoms . However , no impact was identified on cognition and behaviour . Facilitators experienced the sessions as useful and pleasant , and study participants were , in general , attentive , open and collaborative . Discussion Study results showed that organizing st and ardized individual reminiscence therapy with nursing home volunteers was feasible and study participants ' attention and participation were overall good . Further study initiatives to explore the potential of individual reminiscence therapy within a person-centred framework are recommended in order to improve care in nursing homes BACKGROUND Elderly people with cognitive impairments are often associated with depressed mood and are heavy consumers in both medical services and need in caregivers . Reminiscence is believed to be effective in improving the cognition and mood of demented people . OBJECTIVES This study tested the hypothesis that structured group reminiscence therapy can prevent the progression of cognitive impairment and enhance affective function in the cognitively impaired elderly . METHODS A r and omized controlled trial ( RCT ) based on a two group pre- and post-test design was used . The experimental subjects underwent eight group sessions , one session per week . The measurements were performed using Mini-Mental State Examination ( MMSE ) , Geriatric Depression Scale short form ( GDS-SF ) , and Cornell Scale for Depression in Dementia ( CSDD ) . RESULTS The sample consisted of 102 subjects , with 51 in the experimental group and 51 in the control group . Results demonstrated that the intervention significantly affected cognitive function and affective function as measured by MMSE and CSDD ( p = 0.015 and 0.026 ) , indicating that the cognitive function of the experimental subjects increased and their depressive symptoms diminished following intervention . CONCLUSION Participation in reminiscence activities can be a positive and valuable experience for demented older persons . Consequently , the development of a structured care program for elderly persons with cognitive impairment and the need for long-term care is essential . Thus , health providers in long-term care facilities should be trained in reminiscence group therapy , and to be able to deliver such a program to the targeted group The purpose of this study was , conducted with experimental design , to investigate the effect of reminiscence therapy on cognition , depression , activities of daily living of institutionalized mild and moderate Alzheimer patients . The study was conducted with a total of 62 patients ( 31 intervention group and 31 control group ) in four home care in Ankara , Turkey . Study was done between the July 1 , 2013 and December 20 , 2014 . Reminiscence therapy sessions were held with groups consists of 4 - 5 patients , once a week with 30 - 35 minute duration for 12 weeks . St and ardized Mini Mental Test was used in sample selection . Patients were listed through their mini mental test scores , and r and omized as odd numbers to control group and even numbers to intervention group . Data were collected with forms developed by research er ‘ Data Sheet ’ and ‘ Activities of Daily Living Follow-up Form ’ as well as scales ‘ St and ardized Mini Mental Test ’ and ‘ Geriatric Depression Scale ’ . Chi-square , Mann Whitney-U test , variance analyses in repeated measures and Bonferroni tests were used for analysis . The increase in mean St and ardized Mini Mental Test score and the decrease in mean Geriatric Depression Scale score of the individuals in the intervention group compared to the control group at the end of the reminiscence therapy was statistically significant ( P < 0.05 ) . At the end of reminiscence therapy sessions , increase in cognition and decrease in depression were found statistically significant in intervention group |
2,116 | 32,110,374 | SH in early childhood-onset diabetes , especially seizures and coma , was associated with poorer memory ( verbal and visuospatial ) , as well as verbal intelligence .
Among adult-onset diabetes , SH was associated with poorer cognitive performance in the older age ( > 55 years ) group only .
Early versus late exposure to SH had a significant association with cognitive dysfunction ( CD ) .
NSH and NH did not have any significant association with CD , while impaired awareness of hypoglycaemia was associated with poorer memory and cognitive-processing speeds .
Conclusion The effect of SH on cognitive function is age dependent . | Background The effect of prior hypoglycaemia on cognitive function in type 1 diabetes is an important unresolved clinical question .
In this systematic review , we aim ed to summarize the studies exploring the impact of prior hypoglycaemia on any aspect of cognitive function in type 1 diabetes . | Ninety-seven patients with insulin dependent diabetes mellitus ( IDDM ) were r and omized to intensified conventional treatment ( ICT , n = 44 ) or regular treatment ( RT , n = 53 ) . The mean HbA1c level ( + /- SEM ) was reduced from 9.5 + /- 0.2 % to 7.4 + /- 0.1 % in the ICT group ( P less than 0.001 ) , and from 9.4 + /- 0.2 % to 9.0 + /- 0.2 % ( P less than 0.01 ) in the RT group . The difference between the groups was significant ( P less than 0.001 ) . During a period of 3 years , 57 % of the ICT patients ( 95 % confidence interval 44 - 73 % ) and 23 % of the RT patients ( 95 % CI , 11 - 34 % ) ( P less than 0.001 ) had at least one episode of serious hypoglycaemia , with the need for third-party assistance or result ing in coma . Eighteen of the 32 ICT patients who initially had adrenergic symptoms during hypoglycaemia changed to predominantly neuroglycopenic symptoms . This was the case with only 8 of 38 RT patients ( P less than 0.01 ) . The change in symptoms was related to the increased frequency of serious hypoglycaemia , but neither symptoms nor frequency of hypoglycaemia bor any relationship to insulin dose , body mass index , duration of diabetes or autonomic nerve function . The results of several neuropsychological tests did not differ between the groups at baseline , and did not change during the study . There were no signs of deteriorating cognitive function in the patients with serious hypoglycaemic episodes OBJECTIVE —In this study , we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospect ively from diagnosis . RESEARCH DESIGN AND METHODS —We studied type 1 diabetic ( n = 106 ) and control subjects ( n = 75 ) with no significant group difference on IQ at baseline 12 years previously by using the Wechsler Abbreviated Scale of General Intelligence , magnetic resonance spectroscopy and imaging , and metabolic control data from diagnosis . RESULTS —Type 1 diabetic subjects had lower verbal and full scale IQs than control subjects ( both P < 0.05 ) . Type 1 diabetic subjects had lower N-acetylaspartate in frontal lobes and basal ganglia and higher myoinositol and choline in frontal and temporal lobes and basal ganglia than control subjects ( all P < 0.05 ) . Type 1 diabetic subjects , relative to control subjects , had decreased gray matter in bilateral thalami and right parahippocampal gyrus and insular cortex . White matter was decreased in bilateral parahippocampi , left temporal lobe , and middle frontal area ( all P < 0.0005 uncorrected ) . T2 in type 1 diabetic subjects was increased in left superior temporal gyrus and decreased in bilateral lentiform nuclei , cau date nuclei and thalami , and right insular area ( all P < 0.0005 uncorrected ) . Early-onset disease predicted lower performance IQ , and hypoglycemia was associated with lower verbal IQ and volume reduction in thalamus ; poor metabolic control predicted elevated myoinositol and decreased T2 in thalamus ; and older age predicted volume loss and T2 change in basal ganglia . CONCLUSIONS —This study documents brain effects 12 years after diagnosis in a type 1 diabetic sample whose IQ at diagnosis matched that of control subjects . Findings suggest several neuropathological processes including gliosis , demyelination , and altered osmolarity Background Prospect i ve memory is that memory which is required to carry out intended actions and is therefore essential in carrying out the daily activities required in the self-management of type 1 diabetes mellitus ( T1DM ) . This study aim ed to identify the relationships between prospect i ve memory and diabetic control in children with T1DM . Method 94 children aged 6–18 years with T1DM completed an innovative prospect i ve memory screen , PROMS , and a series of cognitive tests . Parents answered question naires about their children 's diabetic histories and cognitive skills . Results No association between total PROMS score and glycemic control was found . Lower HbA1C was associated with higher ( better ) scores on the 20 minute event-based task on the PROMS . Parental concerns about working memory and metacognition in their children were mirrored by higher HbA1C . Conclusions This study suggests that there may be an association between glycemic control and prospect i ve memory for event based tasks . Additional studies need to be done to determine reproducibility , causality , and if prospect i ve memory based interventions can improve diabetic control Declining incidences in Europe of overt nephropathy , proliferative retinopathy , and mortality in type 1 diabetes have recently been reported . However , comparable data for the U.S. and trend data for neuropathy and macrovascular complications are lacking . These issues are addressed using the prospect i ve observational Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study . Participants were stratified into five cohorts by diagnosis year : 1950–1959 , 1960–1964 , 1965–1969 , 1970–1974 , and 1975–1980 . Mortality , renal failure , and coronary artery disease ( CAD ) status were determined on the complete cohort ( n = 906 ) at 20 , 25 , and 30 years . Overt nephropathy , proliferative retinopathy , and neuropathy were assessed at 20 and 25 years on the subset of participants with a clinical examination . There was a decreasing trend by diagnosis year for mortality , renal failure , and neuropathy across all time intervals ( P < 0.05 ) , with the 1950–1959 cohort having a fivefold higher mortality at 25 years than the 1970s ’ cohorts . Proliferative retinopathy and overt nephropathy showed nonsignificant declines at 20 years ( P < 0.16 and P < 0.13 , respectively ) and no change at 25 years . CAD event rates , which were lower than the other complications , also showed no trend . Although some type 1 diabetes complications ( mortality , renal failure , and neuropathy ) are declining , others ( CAD , overt nephropathy , and proliferative retinopathy ) show less favorable changes by 30 years OBJECTIVE —The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13–19 years at entry in the Diabetes Control and Complications Trial ( DCCT ) . RESEARCH DESIGN AND METHODS —This was a longitudinal study involving 249 patients with type 1 diabetes who were between 13 and 19 years old when they were r and omly assigned in the DCCT . Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study , ∼18 years later , were compared with baseline performance . We assessed the effects of the original DCCT treatment group assignment , mean A1C values , and frequency of severe hypoglycemic events on eight domains of cognition . RESULTS —There were a total of 294 reported episodes of coma or seizure . Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain . As in a previous analysis of the entire study cohort , higher A1C values were associated with declines in the psychomotor and mental efficiency domain ( P < 0.01 ) ; however , the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis . CONCLUSIONS —Despite relatively high rates of severe hypoglycemia , cognitive function did not decline over an extended period of time in the youngest cohort of patients with type 1 diabetes BACKGROUND Lowered neuropsychological performance is evident in youth with type 1 diabetes , although evidence for associations with specific illness variables is inconsistent . This study examined the neuropsychological profiles of a cohort of youth with type 1 diabetes studied prospect ively from diagnosis 12 yr previously . METHODS A total of 106 youth with type 1 diabetes and 75 healthy controls participated . There were no significant group differences on Full-scale IQ assessed on study entry 12 yr previously , current socioeconomic status , gender distribution , or age . Neuropsychological tests assessed eight cognitive domains : verbal abilities , perceptual reasoning , new learning , working memory , non-verbal processing speed , mental efficiency , divided attention , and sustained attention . Episodes of serious hypoglycemia and HbA(1c ) levels were recorded from diagnosis . RESULTS Youth with type 1 diabetes performed more poorly than controls on working memory ( p < .05 ) . Early onset diabetes was related to poorer sustained ( p < .001 ) and divided attention ( p = .001 ) , new learning , and mental efficiency ( both p < .05 ) . Hypoglycemia was found to adversely effect verbal abilities , working memory , and non-verbal processing speed ( all p < .05 ) . Poorer working memory was associated with hyperglycemia ( p < .05 ) . Youth with any combination of two or three illness risk factors ( i.e. , early onset diabetes , hypo- , hyperglycemia ) , performed more poorly than controls and youth with no or one risk on verbal abilities , working memory , and mental efficiency . CONCLUSIONS This study documents poorer neuropsychological performance and its association with illness risk factors in youth with type 1 diabetes . Findings suggest that early disease onset and hypoglycemia impact on the developing central nervous system , with hyperglycemia playing a lesser role Abstract . Aims /hypothesis : Good metabolic control in diabetic children is already crucial before puberty to prevent diabetic complications later in life . However , tight metabolic control could increase the risk of severe hypoglycaemia , which might be responsible for impaired intellectual performance later in life . The purpose of this prospect i ve longitudinal study was to evaluate the relevance of long-term metabolic control and hypoglycaemia possibly affecting the intellectual development of young children with Type I ( insulin-dependent ) diabetes mellitus . Methods : The intellectual development in 64 diabetic children between the ages of 7 and 16 years was assessed at least four times using the German version of the Hamburg Wechsler intelligence scale for preschool children , Children-Revised and by the “ Adaptives Intelligenz Diagnostikum ” ( Adaptive Intelligence Diagnosticum ) . Data were analysed longitudinally compared with a control group . Results : A significant decline in performance by age 7 and in verbal intelligence quotient between age 7 and 16 years was observed in diabetic boys diagnosed before the age of 6 but not in those diagnosed later and not in diabetic girls . The deterioration of intellectual performance in boys diagnosed at a very young age was not associated with the occurrence of severe hypoglycaemic episodes but was correlated with the degree of metabolic deterioration at diagnosis and with high long-term average of glycated haemoglobin . Conclusion /interpretation : Our study in diabetic children shows that the male sex , diagnosis at a young age , metabolic condition at diagnosis and long-term metabolic control , rather than experienced hypoglycaemic attacks are risk factors for intellectual development . [ Diabetologia ( 2002 ) 45 : 108–114 OBJECTIVE This study examined illness-related change in intelligence quotient ( IQ ) in a cohort of youth with type 1 diabetes studied prospect ively from disease onset in childhood to follow-up 12 years later in late adolescence/early adulthood . RESEARCH DESIGN AND METHODS Participants included type 1 diabetes patients ( n = 95 ; mean age at follow-up 21.3 years ) and healthy control participants ( HCs ; n = 67 ; mean age at follow-up 21.0 years ) from a cohort followed prospect ively . Measures included Wechsler Preschool and Primary Scale of Intelligence-Revised , Wechsler Intelligence Scale for Children-Revised , and Wechsler Abbreviated Scale of Intelligence and prospect i ve collection of data on metabolic control history . RESULTS Young people with type 1 diabetes showed greater decline in verbal IQ ( VIQ ) and full-scale IQ ( FSIQ ) , but not performance IQ ( PIQ ) , than HCs . Within the diabetes group , a younger age at diabetes onset was associated with a decline in PIQ and FSIQ ( P ≤ 0.001 ) . A history of hypoglycemic seizures was associated with a decline in VIQ ( P = 0.002 ) . Long-term metabolic control was not associated with changes in IQ . Interaction terms were not significant , suggesting no moderating effect of one diabetes-related variable over another . CONCLUSIONS The presence of diabetes may negatively influence some aspects of IQ over time . Specific illness risk factors , such as an earlier age of disease onset and a history of hypoglycemic seizures , appear to put the young person at greater risk . Academic progress of children identified as at risk should be monitored and educational supports provided if necessary OBJECTIVE Acute hypoglycemia in humans impairs cognitive functions and alters mood states . The time required for cognitive functions and moods to return to normal after an acute episode of severe hypoglycemia is unknown . RESEARCH DESIGN AND METHODS Cognitive functions and moods were studied prospect ively in 20 subjects with insulin-treated diabetes who had recently experienced a spontaneous episode of severe hypoglycemia ( " hypo " subjects ) and 20 matched control subjects with insulin-treated diabetes who had not experienced severe hypoglycemia during the preceding year . The hypo subjects had a history of a greater number of episodes of severe hypoglycemia ( P = 0.000 ) . Cognitive function tests and mood scales were administered at 1.5 , 9 , and 30 days after the severe hypoglycemia and at similar intervals for the control subjects . RESULTS For most of the cognitive tests , no evidence of a " hangover " effect of the acute hypoglycemia on cognitive function was observed ( P > 0.05 ) . A trend was noted for levels of hedonic tone ( P = 0.082 ) and energetic arousal ( P = 0.053 ) to improve with time in the hypo subjects but not in the control subjects . However , the hypo subjects had chronically elevated levels of depression ( P = 0.011 ) and anxiety ( P = 0.049 ) and persistently performed more poorly in several cognitive tests , such as the Digit Symbol Test ( P = 0.009 ) and the Stroop Task ( P = 0.007 ) . CONCLUSIONS These results suggest that , in general , recovery from any acute cognitive decrement after severe hypoglycemia was complete by 1.5 days . The cognitive decrements and altered mood states noted in the hypo subjects may be persistent and may be a consequence of previous exposure to recurrent episodes of severe hypoglycemia BACKGROUND We compared glycemia , treatment satisfaction , sleep quality , and cognition using a nighttime And roid-based hybrid closed-loop system ( And roid-HCLS ) with sensor-augmented pump with low-glucose suspend function ( SAP-LGS ) in people with type 1 diabetes . MATERIAL S AND METHODS An open-label , prospect i ve , r and omized crossover study of 16 adults ( mean [ SD ] age 42.1 [ 9.6 ] years ) and 12 adolescents ( 15.2 [ 1.6 ] years ) was conducted . All participants completed four consecutive nights at home with And roid-HCLS ( proportional integral derivative with insulin feedback algorithm ; Medtronic ) and SAP-LGS . PRIMARY OUTCOME percent continuous glucose monitoring ( CGM ) time ( 00:00 - 08:00 h ) within target range ( 72 - 144 mg/dL ) . Secondary endpoints : percent CGM time above target ( > 144 mg/dL ) ; below target ( < 72 mg/dL ) ; glycemic variability ( SD ) ; symptomatic hypoglycemia ; adult treatment satisfaction ; sleep quality ; and cognitive function . RESULTS The primary outcome for all participants was not statistically different between And roid-HCLS and SAP-LGS ( mean [ SD ] 59.4 [17.9]% vs. 53.1 [18]% ; p = 0.14 ) . Adults had greater percent time within target range ( 57.7 [18.6]% vs. 44.5 [14.5]% ; p < 0.006 ) ; less time above target ( 42.0 [18.7]% vs. 52.6 [16.5]% ; p = 0.034 ) ; lower glycemic variability ( 35 [ 10.7 ] mg/dL vs. 46 [ 10.7 ] mg/dL ; p = 0.003 ) ; and less ( median [ IQR ] ) time below target ( 0.0 [0.0 - 0.4]% vs. 0.80 [0.0 - 3.9]% ; p = 0.025 ) . In adolescents , time below target was lower with And roid-HCLS vs. SAP-LGS ( 0.0 [0.0 - 0.0]% vs. 1.8 [0.1 - 7.9]% ; p = 0.011 ) . Nocturnal symptomatic hypoglycemia was less ( 1 vs. 10 ; p = 0.007 ) in adolescents , but not adults ( 5 vs. 13 ; p = 0.059 ) . In adults , treatment satisfaction increased by 10 points ( p < 0.02 ) . Sleep quality and cognition did not differ . CONCLUSIONS And roid-HCLS in both adults and adolescents reduced nocturnal hypoglycemia and , in adults , improved overnight time in target range and treatment satisfaction compared with SAP-LGS A series of seven psychometric tests , to evaluate mental concentration and the ability to retain selective attention , lexical fluency , wordlist memorizing and psychomotor speed , was performed on 25 non-diabetic control subjects and 55 insulin-dependent diabetes ( IDD ) patients of similar social background and professional status . When tested , none of the diabetics was hypoglycaemic and these patients were divided into two groups : Group I : 30 IDD patients unaware of hypoglycaemia , and experiencing frequent and severe episodes of hypoglycaemia . Group II : 25 IDD patients aware of hypoglycaemia . Groups I and II had experienced the disease for the same period of time ( 17 + /- 13 vs. 14 + /- 11 years , respectively ) and they had similar HbA1c levels ( 7.14 + /- 1.25 % vs. 8.6 + /- 1.88 % , respectively ) and degenerative complications . Compared with the scores of the controls , the Group I scores were lower in four tests : trail-making part A ( psychomotor speed ; P less than 0.001 ) and part B ( retaining selective attention ; P less than 0.01 ) , lexical fluency ( P less than 0.01 ) and Rey auditory-verbal learning test ( wordlist learning ; P less than 0.05 ) . Group II scores were lower in two tests : trail-making part A ( P less than 0.01 ) and part B ( P less than 0.05 ) . In word memorizing , the performance of Group I was inferior to that of Group II ( P less than 0.05 ) . In general , these psychometric tests showed that IDD scores were lower than those of the controls , with an average of 67 % for Group II and 80 % for Group I. Chronic hyperglycaemia and severe hypoglycaemia may have a deleterious effect on cognitive performance . In particular , several severe episodes of hypoglycaemia could be responsible for permanent memory impairment Intensive therapy for insulin-dependent diabetes mellitus ( IDDM ) delays the onset and slows the progression of long-term complications , including diabetic retinopathy , nephropathy , and neuropathy [ 1 ] . However , the implementation of this regimen increases the risk for severe hypoglycemia [ 2 , 3 ] . Severe hypoglycemia is particularly problematic because of its potential influence on the integrity of the central nervous system . Not only is severe hypoglycemia associated with a transient reduction in cognitive function that adversely affects activities of daily living , including driving [ 4 , 5 ] , but , if left untreated , it may also lead to clinical ly significant brain damage [ 6 - 8 ] . Although animal studies have provided the most compelling evidence for hypoglycemia-induced brain dysfunction [ 9 ] , investigators of several recent cross-sectional studies have concluded that five or more episodes of severe hypoglycemia may be associated with mild cognitive impairment , as measured by performance on neuropsychological tests [ 10 , 11 ] . To date , only one group of investigators has directly assessed the long-term effects of intensive diabetes therapy on cognitive functioning . Reichard and associates [ 12 ] examined 5-year follow-up data from 96 patients participating in the Stockholm Diabetes Intervention Study ( SDIS ) . In this clinical trial , intensive diabetes therapy ( 3 to 4 injections/d ) was compared with conventional treatment ( 1 to 2 injections/d ) . Despite the significantly higher occurrence of severe hypoglycemia in the intensive therapy group ( 77 % compared with 56 % ) , the 52 patients in that group did no worse on neuropsychological measures than the 44 patients in the st and ard treatment group . These negative findings remain controversial . Deary and associates [ 13 ] have suggested that the failure of Reichard and colleagues [ 12 ] to find meaningful between-group differences may have been a consequence of the study 's small sample size and result ant low statistical power , the unusually high incidence of hypoglycemia in the st and ard treatment group , and the use of a test battery that might have been insensitive to early changes in cognitive functioning . Each of these potential problems has been obviated in the Diabetes Control and Complications Trial ( DCCT ) . For 9 years , 1441 adolescents and adults with IDDM were followed at 29 clinical centers in the United States and Canada . Half the patients were r and omly assigned to receive intensive diabetes therapy , the other half to receive conventional treatment . Throughout the study , the risk for severe hypoglycemia was found to be approximately three times higher in the intensive treatment group than in the conventional treatment group [ 1 ] . The neuropsychological status of each patient was evaluated on two to five occasions ( at baseline ; years 2 , 5 , and 7 ; and study end ) by using an extensive battery of well-known neuropsychological tests selected for their sensitivity for neurocognitive deficits associated with hypoglycemia [ 14 ] . The analyses were done to answer two questions : 1 ) Did intensive therapy differentially affect neuropsychological functioning ? and 2 ) Was the number of episodes of severe hypoglycemia related to the degree of neuropsychological impairment ? Methods Study Sample Patients recruited for the DCCT were 13 to 39 years of age , had had IDDM for 1 to 15 years , and were in generally good health [ 1 ] . Exclusion criteria were advanced retinopathy , nephropathy , or neuropathy ; a history of drug or alcohol abuse ; psychotic episodes ; eating disorders ; epilepsy ; recurrent episodes of ketoacidosis ; and recurrent episodes of coma or seizure due to hypoglycemia . In the first 278 r and omly assigned patients followed for 12 months , a history of severe hypoglycemia was identified as a risk factor for severe hypoglycemia [ 15 ] . Potential volunteers were subsequently excluded if they had had more than two episodes of hypoglycemic seizure or coma in the previous 2 years . The demographic and clinical characteristics of the 1441 patients are listed in Table 1 . Table 1 . Demographic and Clinical Characteristics of Patients at Study Entry * Extent of Follow-up The entire cohort of 1441 patients was followed for 3.5 to 9 years ( mean , 6.5 years ) , yielding approximately 9300 patient-years of observation . Two hundred sixty-eight patients ( 19 % of the total cohort ) were studied for 9 years , and 1088 ( 76 % ) were studied for 5 years . Almost all patients ( 99.7 % ) were followed for at least 3 years . Final follow-up study data were collected on 1422 patients ( 99 % of the total cohort ) . Of the 19 patients who did not complete the study , 8 dropped out and 11 died . More than 95 % of expected visits were held over the 9-year study period , and 98 % of the expected neuropsychological protocol s were completed . Adherence to Assigned Treatment We r and omly assigned 711 patients to receive intensive treatment , which consisted of insulin administered three or more times per day by injection or by continuous subcutaneous infusion with an external pump . Blood glucose levels were monitored four or more times per day , and the results , coupled with anticipated meal content and exercise , were used to adjust the insulin dose . Treatment goals were prepr and ial blood glucose levels between 3.89 and 6.66 mmol/L , postpr and ial blood glucose levels less than 9.99 mmol/L , a weekly 0300 h measurement greater than 3.61 mmol/L , a monthly measured glycosylated hemoglobin ( HbA1c ) level within the nondiabetic range ( < 6.05 % ) , and avoidance of severe hypoglycemia . Conventional therapy ( 730 patients ) consisted of one or two daily insulin injections ; the goal was freedom from symptoms of hyperglycemia and frequent or severe hypoglycemia . The intensive and conventional treatment groups maintained a separation of median HbA1c level of about 2 percentage points throughout the follow-up period ( 7.1 % compared with 9.0 % ; P < 0.001 ) [ 1 ] . Patients ' adherence to r and omly assigned treatment was high ; more than 97 % of study time was spent receiving the assigned therapy [ 1 ] . Definition and Frequency of Severe Hypoglycemia All episodes of severe hypoglycemia were reported to the Coordinating Center as soon as possible after their occurrence . Severe hypoglycemic episodes were defined as those in which the patient had incapacity sufficient to require the assistance of another person . In addition , the definition of severe hypoglycemia required that 1 ) the blood glucose level was measured and found to be less than 2.78 mmol/L or 2 ) the clinical manifestations were reversed by the administration of oral carbohydrate , subcutaneous glucagon , or intravenous glucose . Approximately one third of severe hypoglycemic episodes involved coma , seizure , or suspected seizure . In the intensive treatment group , 61 severe hypoglycemic episodes occurred per 100 patient-years compared with 19 episodes per 100 patient-years in the conventional treatment group ( relative risk , 3.28 [ 95 % CI , 2.65 to 4.05 ] ; P < 0.001 ) [ 16 ] . In the intensive treatment group , 16 severe hypoglycemic episodes involving coma , seizure , or suspected seizure occurred per 100 patient-years compared with 5 such episodes in the conventional treatment group ( relative risk , 3.02 [ CI , 2.36 to 3.86 ] ; P < 0.001 ) [ 16 ] . Neuropsychological Test Protocol Neuropsychological testing was done by trained personnel at baseline ; years 2 , 5 , and 7 ; and study end . The Central Neuropsychological Coding Unit trained and certified the personnel at the clinical centers . Results from the final assessment were assigned to the closest year of expected scheduled neuropsychological evaluation , up to year 9 . The test protocol , which required 4 to 5 hours to complete , included the Wechsler Adult Intelligence Scale [ 17 ] for patients 16 years of age or older ; the Wechsler Intelligence Scale for Children , Revised [ 18 ] , for patients younger than 16 years of age ; four subtests ( category test , tactual performance test , trail making test , and finger tapping test ) from the Halstead-Reitan Neuropsychological Battery [ 19 ] ; the digit vigilance subtest from the Lafayette Clinic Repeatable Battery [ 20 ] ; the logical memory and visual reproduction subtests from the Wechsler Memory Scale [ 21 ] ; the arithmetic subtest from the Wide Range Achievement Test [ 22 ] ; the Grooved Pegboard Test [ 23 ] ; the Verbal Fluency Test [ 24 ] ; and several additional specialized measures ( Symbol Digit Learning Test , Four-Word Short-Term Memory Test , Embedded Figures Test ) [ 25 ] . Tests were administered in a fixed order , with rest breaks scheduled at 45- to 60-minute intervals . The same battery of tests was administered at each evaluation . Capillary blood glucose levels were monitored to rule out the presence of hypoglycemia during testing . The tests were scored by technicians at the Central Neuropsychological Coding Unit who were masked to treatment assignments . These results were sent to the Coordinating Center , where the data were entered , verified , and edited for out-of-range values and other errors . Outcome Measurements Clinical ly Rated Neuropsychological Worsening We had initially planned that all neuropsychological test protocol s would be rated by a team of expert clinicians to determine the presence of a clinical ly significant change in functioning between baseline and re assessment as part of a program to monitor safety . However , during the feasibility phase , we found that the neuropsychological tests could not be rated quickly enough to meet safety needs . We therefore developed a computer-based screening algorithm to identify patients with a high probability of neuropsychological worsening [ 26 ] . Protocol s so identified were review ed by two expert clinical neuropsychologists who independently rated each protocol for change from baseline . If a protocol was rated as significantly worsening since baseline , the local center was notified so that additional neurologic or psychological studies could be done and the patient could be more closely monitored . This screening process was OBJECTIVE To investigate whether severe hypoglycemia in young children with early-onset type 1 diabetes ( T1DM ) is associated with subsequent abnormalities in cognitive status . STUDY DESIGN Recruitment was from a large population -based data base of children and adolescents with T1DM . Children and adolescents with early-onset T1DM ( < 6 years ) were eligible for the study . Diabetic individuals ( n = 41 ) with a prospect ively documented history of seizure or coma were compared with peers with no history of severe hypoglycemic events ( n = 43 ) . A comprehensive test battery of learning and memory was used together with intellectual and behavioral measures . RESULTS No significant group differences were revealed on the intellectual , memory , or behavioral measures . Similarly , those participants with a history of early first seizure did not differ from their peers with no seizures . There were no significant group differences on the memory subtests that were examined given their potential sensitivity to compromised hippocampal function . CONCLUSIONS There was no clear evidence from this cohort that episodes of seizure or coma , even those occurring in very early childhood , result ed in broad cognitive dysfunction , nor was there evidence of specific memory difficulties at the time of testing in children and adolescents with early-onset T1DM OBJECTIVE To identify type 1 diabetes-related predictors of change in the neuropsychological profiles of children over the first 2 years of the illness . RESEARCH DESIGN AND METHODS Children ( n = 116 ) aged 3 - 14 years were assessed soon after diagnosis and re-evaluated 2 years later to examine relationships between illness variables , such as age of onset and metabolic control history , and changes in neuropsychological status over the first 2 years of type 1 diabetes . RESULTS Illness variables were significant predictors of change in neuropsychological test scores within 2 years of onset of type 1 diabetes . Age of onset of type 1 diabetes predicted negative change on Performance Intelligence Quotient , whereas both recurrent severe hypoglycemia and chronic hyperglycemia were associated with reduced memory and learning capacity . CONCLUSIONS These results suggest that the relationship between metabolic control and neuropsychological risk is nonlinear in that children with either recurrent severe hypoglycemia or chronically elevated blood sugars exhibit negative changes in their neuropsychological profiles . Onset of type 1 diabetes very early in life adds another dimension of risk , particularly affecting the acquisition of visuospatial skills Investigated the relationship between disease variables , neuropsychological performance , and psychosocial status in adolescents with Insulin Dependent Diabetes Mellitus ( IDDM ) . The study group consisted of 85 adolescents , aged 14 to 16.5 years who had been diabetic for longer than 12 months . Parameters of both recent and long-term metabolic control were determined , including diabetic incidents such as severe hypoglycemia or ketoacidosis . The mothers completed st and ardised measures of adolescent adjustment , and the adolescents provided self-reports of psychosocial status . Neuropsychological functioning was evaluated with st and ardised tests of verbal and nonverbal intelligence , memory and new learning , visuo-graphic skills , mental flexibility , and problem-solving ability . Using retrospective accounts of disease history , there was no relationship between neuropsychological functioning and variables such as age of onset , chronic poor control , or major metabolic crises . The findings emphasise the need for a long-term , prospect i ve study of a cohort of diabetic children from the time of diagnosis to clarify causal relationships , if any , between illness variables , neuropsychological performance , and psychosocial factors OBJECTIVE To test the conclusion that there is no association between multiple episodes of severe hypoglycemia and cognitive decrements by reanalyzing the data from the Diabetes Control and Complications Trial ( DCCT ) with psychometrically vali date d cognitive factors and to conduct a novel analysis of the association between individual differences in baseline cognitive ability and episodes of severe hypoglycemia documented after baseline . RESEARCH DESIGN AND METHODS The factor structure of cognitive ability in the neuropsychological data from the DCCT study was derived . Four cognitive factors ( spatial ability , processing speed , memory , and verbal ability ) were extracted . Changes in patients ' cognitive scores for each year of follow-up were obtained , and paired comparisons of these change scores were performed between groups experiencing zero and five or more hypoglycemic episodes . The association between cognitive ability at baseline and number of subsequent episodes of severe hypoglycemia was also examined . RESULTS Repeated episodes of hypoglycemia were found not to be associated with cognitive decline in any of the vali date d cognitive factors . No significant association was found between prospect ively documented numbers of severe hypoglycemic episodes and baseline cognitive ability level . CONCLUSIONS Repeated episodes of hypoglycemia were not related to cognitive decrement , and initial mental ability level was not associated with eventual numbers of hypoglycemic episodes in this group of patients Intensive insulin treatment of IDDM is associated with increased frequency of hypoglycemic coma . The extent of possible cerebral sequelae after recovery is still unknown . We studied the impact of previous hypoglycemic coma on neurophysiological measures of cognitive brain function in 108 patients with adult-onset IDDM receiving intensive insulin treatment . In the study , 55 IDDM patients ( age 38 + /- 14 years , mean + /- SD ) who had a history of > or = 1 ( median 3 , range 1 - 35 ) comatose hypoglycemic event were compared with 53 IDDM patients ( age 34 + /- 12 years ) with no history of hypoglycemic events using P300 event-related potentials and psychometric tests ( the Mini-Mental State Exam and trailmaking test , part A ) . Findings on these patients were compared with those from 108 matched healthy control subjects . No difference was observed in P300 latencies and psychometric tests between patients with and without a history of hypoglycemic coma ( P300 latency , 346 vs. 342 ms ; trailmaking test , 31 vs. 30 s ; Mini-Mental State Exam , 29.5 vs. 29.6 ; NS ) . In diabetic patients , however , P300 latencies were delayed compared with those of healthy control subjects ( 344 vs. 332 ms ; P < 0.001 ) and were correlated to diabetes duration but not to total hypoglycemic episodes . Scores on the Mini-Mental State Exam ( 29.5 vs. 29.6 ; P = 0.59 ) and trailmaking test ( 31 vs. 28 s ; P = 0.10 ) were not different between patients and control subjects . In conclusion , previous episodes of hypoglycemic coma are not associated with permanent impairment of cognitive brain function in patients with adult-onset IDDM receiving intensive insulin treatment compared with patients without such episodes . Cognitive brain function , however , is sub clinical ly impaired in relation to duration of diabetes In a previous retrospective study , severe hypoglycemia ( SH ) was associated with decreased long-term spatial memory in children with type 1 diabetes mellitus ( T1DM ) . In this study , we tested the hypothesis that prospect ively ascertained SH would also be associated with decreased spatial long-term memory over time . Children with T1DM ( n = 42 ) and sibling controls ( n = 25 ) performed a spatial delayed response ( SDR ) task with short and long delays and other neuropsychological tests at baseline and after 15 months of monitoring . Extreme glycemic events and other medical complications were recorded prospect ively during follow-up . Fourteen T1DM children experienced at least one episode of SH during the follow-up period ( range = 1 - 5 ) . After controlling for long-delay SDR performance at baseline , age , gender , and age of onset , the presence of SH during the prospect i ve period was statistically associated with decreased long-delay SDR performance at follow-up ( semipartial r = -0.38 , p = 0.017 ) . This relationship was not seen with short-delay SDR or with verbal or object memory , attention , or motor speed . These results , together with previously reported data , support the hypothesis that SH has specific , negative effects on spatial memory skills in T1DM children |
2,117 | 22,212,682 | These findings suggest that extended care is a viable and efficacious solution to addressing long-term maintenance of lost weight . | Behavioural weight management interventions consistently produce 8 - 10 % reductions in body weight , yet most participants regain weight after treatment ends .
One strategy for extending the effects of behavioural interventions has been the provision of extended care .
The current study is a systematic review and meta- analysis of the literature on the effect of extended care on maintenance of weight loss . | BACKGROUND Effective clinical weight management approaches are needed to reach African-Americans . METHODS African-Americans recruited through outpatient practice s for a culturally-adapted Healthy Eating and Lifestyle Program were offered 10 weekly weight loss classes ( Phase 1 ) with the option of continuing for another 8 - 18 months ( Phase 2 ) in a r and omized comparison of further group counseling or staff-facilitated self-help vs. follow-up clinic visits only . RESULTS Of 237 enrollees ( 91 % women ; mean age 43.5 years ; mean body mass index 38.0 kg/m(2 ) ) , 70 [ corrected ] attended no classes or only the first Phase 1 class , 134 provided Phase 1 follow-up data , 128 were r and omized in Phase 2 , and 87 provided final follow-up data ( " completers " ) . Mean weight changes for completers were : -1.5 ( P < 0.001 ) , + 0.3 ( P = 0.47 ) , and -1.2 ( P = 0.04 ) kg , respectively , for Phase 1 , Phase 2 , and overall ( baseline to final visit ; average 18 months total duration ) , with no Phase 2 treatment effect ( P = 0.55 ) . Final study weight was > or = 5 % below baseline for 25 % of completers and was strongly predicted by Phase 1 weight loss . CONCLUSIONS Weight loss achieved in Phase 1 was maintained even with relatively minimal follow-up contact . Increasing the percent who achieve clinical ly significant weight loss initially would improve long-term results This article reports the results of two studies evaluating strategies to improve maintenance of weight loss . Study 1 evaluated the effect of frequent contact with patients through phone calls design ed to promote adherence to self-monitoring ; Study 2 evaluated a crisis intervention model , where subjects could obtain food boxes during high-risk periods to simplify dietary adherence . All subjects had originally participated in an initial six-month behavioral weight control program conducted at the University of Minnesota or at the University of Pittsburgh and had lost > 4.0 kg . Subjects from the University of Minnesota ( N=53 ) were r and omly assigned to either a year-long maintenance program involving weekly phone calls from a staff member or to a no-contact control ( Study 1 ) . Weekly phone calls , which inquired about self-monitoring and current weight , were completed with high frequency ( 76 % completion rate ) ; call completion and self-reported adherence to daily monitoring were negatively associated with weight regain ( r=−0.52 to −0.59 , p<.01 ) . However , weight regain did not differ significantly in the Phone Maintenance versus Control Condition ( + 3.9 kg versus + 5.6 kg , p=.28 ) . Study 2 , conducted at the University of Pittsburgh , involved 47 subjects who were r and omly assigned to a Control or Optional Food Provision Condition . Both groups attended monthly maintenance meetings ; the Food Provision Group had the option of purchasing boxes of food containing five breakfasts and five dinners . Twelve of the 26 subjects in the Food Provision Group purchased these food boxes for at least one month of maintenance . However , weight regain in those people who purchased the box , or in the Food Provision Condition as a whole , did not differ from the Control Condition ( + 4.2 kg for intervention versus + 4.3 kg for control ) . Further research is needed to develop more effective maintenance interventions OBJECTIVE The current study examined ethnic differences in patterns of weight loss and regain in response to an initial behavioral weight loss intervention followed by an extended-care maintenance program . METHODS We analyzed data from 224 women ( African American n = 43 , Caucasian n = 181 ) from rural communities who participated in an initial 6-month lifestyle intervention for obesity and were then r and omized to a face-to-face , telephone , or educational/control extended-care condition . RESULTS African American participants lost less weight during the initial phase of treatment than Caucasian participants ( mean + /- SE = -6.8 + /-.80 vs -10.7 + /- .38 kg , respectively , P = .003 ) . Investigating weight change during month 6 to month 18 , we found a significant interaction between ethnicity and the provision of an extended-care program . Caucasian participants r and omized to either of two extended-care programs regained less weight than those assigned to the control condition ( 1.2 + /- .58 and 4.2 + /- .79 kg , respectively , P=.003 ) , but the provision of extended care did not influence weight regain among African American participants ( 1.9 + /- 1.12 and 1.34 + /- 2.04 kg , respectively , P = .815 ) . CONCLUSION Collectively , these findings suggest that although African American participants lost less weight during the initial phase of treatment , they exhibited better long-term weight-loss maintenance than Caucasian participants . Further , while the provision of extended care successfully enhanced weight maintenance among Caucasian participants , African American participants maintained their initial weight losses regardless of extended care BACKGROUND Since many successful dieters regain the weight they lose , programs that teach maintenance skills are needed . We developed a maintenance program based on self-regulation theory and tested the efficacy of delivering the program face to face or over the Internet . METHODS We r and omly assigned 314 participants who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of three groups : a control group , which received quarterly newsletters ( 105 participants ) , a group that received face-to-face intervention ( 105 ) , and a group that received Internet-based intervention ( 104 ) . The content of the programs in the two intervention groups was the same , emphasizing daily self-weighing and self-regulation , as was the frequency of contact with the groups . The primary outcome was weight gain over a period of 18 months . RESULTS The mean ( + /-SD ) weight gain was 2.5+/-6.7 kg in the face-to-face group , 4.7+/-8.6 kg in the Internet group , and 4.9+/-6.5 kg in the control group , with a significant difference between the face-to-face group and the control group ( 2.4 kg ; 95 % confidence interval [ CI ] , 0.002 to 10.8 ; P=0.05 ) . The proportion of participants who regained 2.3 kg or more over the 18-month period was significantly higher in the control group ( 72.4 % ) than in the face-to-face group ( 45.7 % ; absolute difference , 27 % ; 95 % CI , 14 to 39 ; P<0.001 ) or the Internet group ( 54.8 % ; absolute difference , 18 % ; 95 % CI , 5 to 30 ; P=0.008 ) . Daily self-weighing increased in both intervention groups and was associated with a decreased risk of regaining 2.3 kg or more ( P<0.001 ) . CONCLUSIONS As compared with receiving quarterly newsletters , a self-regulation program based on daily weighing improved maintenance of weight loss , particularly when delivered face to face . ( Clinical Trials.gov number , NCT00067145 [ Clinical Trials.gov ] . The present study compared the relative effectiveness of a therapist-supported maintenance condition with a minimal contact maintenance condition in preventing relapse following an obesity treatment program . Thirty-two subjects who completed an initial 12-week cognitive/behavioral plus aerobic exercise treatment program were matched on absolute weight loss and r and omly assigned to one of two maintenance conditions . Subjects were assessed at pretreatment , posttreatment , and 3 , 6 , and 12 months following posttreatment using measures of weight , blood pressure , and depression . Three- and six-month follow-up results indicated that subjects who participated in the therapist-supported maintenance group continued to lose weight and /or maintained therapy-induced weight loss to a greater degree than control subjects . At the 12-month follow-up assessment therapist-supported subjects maintained therapy-induced weight loss better than the control subjects . These findings suggest that maintenance programs which provide continued contact emphasizing relapse prevention training may be an important adjunct in the maintenance of therapy-induced weight loss OBJECTIVE —The effectiveness of intentional weight loss in reducing cardiovascular disease ( CVD ) events in type 2 diabetes is unknown . This report describes 1-year changes in CVD risk factors in a trial design ed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events . RESEARCH DESIGN AND METHODS —This study consisted of a multicentered , r and omized , controlled trial of 5,145 individuals with type 2 diabetes , aged 45–74 years , with BMI > 25 kg/m2 ( > 27 kg/m2 if taking insulin ) . An intensive lifestyle intervention ( ILI ) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education ( DSE ) condition . RESULTS — Participants assigned to ILI lost an average 8.6 % of their initial weight vs. 0.7 % in DSE group ( P < 0.001 ) . Mean fitness increased in ILI by 20.9 vs. 5.8 % in DSE ( P < 0.001 ) . A greater proportion of ILI participants had reductions in diabetes , hypertension , and lipid-lowering medicines . Mean A1C dropped from 7.3 to 6.6 % in ILI ( P < 0.001 ) vs. from 7.3 to 7.2 % in DSE . Systolic and diastolic pressure , triglycerides , HDL cholesterol , and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants ( all P < 0.01 ) . CONCLUSIONS —At 1 year , ILI result ed in clinical ly significant weight loss in people with type 2 diabetes . This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE . Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk This study compared 2 extended therapy programs for weight management with st and ard behavioral treatment ( BT ) without additional therapy contacts . Participants were 80 obese women who completed 20 weekly group sessions of BT and achieved a mean initial weight loss of 8.74 kg . Participants were r and omly assigned to a no-further-contact condition ( BT only ) or to one of two extended interventions consisting of relapse prevention training ( RPT ) or problem-solving therapy ( PST ) . No significant overall weight-change differences were observed between RPT and BT or between RPT and PST . However , participants who completed the PST intervention had significantly greater long-term weight reductions than BT participants , and a significantly larger percentage of PST participants achieved clinical ly significant losses of 10 % or more in body weight than did BT participants ( 35 % vs. 6 % ) OBJECTIVE This study assessed whether a 5 % to 10 % reduction in initial weight would be associated with as favorable long-term ( i.e. , 100 weeks ) changes in lipids and lipoproteins , as have been observed on a short-term basis ( i.e. , 8 weeks ) . RESEARCH METHODS AND PROCEDURES This was a prospect i ve evaluation of 25 obese women , each of whom had lost > or = 5 % of initial weight during 48 weeks of treatment and had maintained a weight loss of this magnitude at 1-year follow-up ( week 100 ) . Lipids and lipoproteins were obtained at baseline and at weeks 8 , 24 , 48 , and 100 . All participants had a baseline total cholesterol > or = 5.17 mmol/L ( 200 mg/dL ) . RESULTS At the end of the first 8 weeks , weight fell an average of 11.7+/-2.8 % , total cholesterol 20.6+/-7.5 % , low-density-lipoprotein ( LDL ) cholesterol 23.0+/-18.1 % , and triglycerides 26.0+/-20.1 % . At week 48 , weight had fallen to 20.1+/-7.0 % below baseline , but total cholesterol and LDL cholesterol were reduced only 11.5+/-10.4 % and 12.0+/-14.0 % below baseline , respectively . These latter reductions were significantly ( p<0.05 ) smaller than those observed at week 8 , despite the larger weight loss at week 48 . High-density-lipoprotein cholesterol declined significantly ( p<0.05 ) during the first 8 weeks , but returned to baseline values by week 24 . Patients gained 7.4+/-7.4 kg from weeks 48 to 100 , during which time total and LDL cholesterol ( but not triglycerides ) rose significantly ( p<0.05 ) . Patients who , at week 100 , maintained losses > 10 % of initial weight had significantly greater reductions in total and LDL cholesterol values than did patients who maintained losses of only 5 % to 10 % of initial weight . DISCUSSION Results of this study underscore the importance of assessing long-term changes in weight-related health complications when patients have lost weight but are no longer dieting ( and exercising ) as aggressively as they did during the initial months of treatment OBJECTIVE To investigate the efficacy of an Internet weight maintenance program . RESEARCH METHODS AND PROCEDURES Two hundred fifty-five healthy overweight and obese adults ( mean + /- SD BMI , 31.8 + /- 4.1 kg/m(2 ) ) men ( 18 % ; mean + /- SD age , 45.8 + /- 8.9 yrs ) participated in a 6-month behavioral weight control program conducted over interactive television . Treatment was followed by a 12-month weight maintenance program with three conditions : frequent in-person support ( F-IPS ) , minimal in-person support ( M-IPS ) and internet support ( IS ) . Main outcome measures included body weight , program adherence , and social influence components . RESULTS There were no significant differences among the groups in weight loss ( mean + /- SD ) from baseline to 18 months ( 7.6 + /- 7.3 kg vs. 5.5 + /- 8.9 kg vs. 5.1 + /- 6.5 kg , p = 0.23 for the IS , M-IPS , and F-IPS , respectively ) . DISCUSSION Participants assigned to an internet-based weight maintenance program sustained comparable weight loss over 18 months compared with individuals who continued to meet face-to-face . Therefore , the internet appears to be a viable medium for promoting long-term weight maintenance BACKGROUND Rural counties in the United States have higher rates of obesity , sedentary lifestyle , and associated chronic diseases than nonrural areas , yet the management of obesity in rural communities has received little attention from research ers . METHODS Obese women from rural communities who completed an initial 6-month weight-loss program at Cooperative Extension Service offices in 6 medically underserved rural counties ( n = 234 ) were r and omized to extended care or to an education control group . The extended-care programs entailed problem-solving counseling delivered in 26 biweekly sessions via telephone or face to face . Control group participants received 26 biweekly newsletters containing weight-control advice . RESULTS Mean weight at study entry was 96.4 kg . Mean weight loss during the initial 6-month intervention was 10.0 kg . One year after r and omization , participants in the telephone and face-to-face extended-care programs regained less weight ( mean [ SE ] , 1.2 [ 0.7 ] and 1.2 [ 0.6 ] kg , respectively ) than those in the education control group ( 3.7 [ 0.7 ] kg ; P = .03 and .02 , respectively ) . The beneficial effects of extended-care counseling were mediated by greater adherence to behavioral weight-management strategies , and cost analyses indicated that telephone counseling was less expensive than face-to-face intervention . CONCLUSIONS Extended care delivered either by telephone or in face-to-face sessions improved the 1-year maintenance of lost weight compared with education alone . Telephone counseling constitutes an effective and cost-efficient option for long-term weight management . Delivering lifestyle interventions via the existing infrastructure of the Cooperative Extension Service represents a viable means of adapting research for rural communities with limited access to preventive health services . Trial Registration clinical trials.gov Identifier : NCT00201006 The current investigation examined the impact of a weight maintenance intervention ( MI ) design ed to empower people to create a personal healthy food and physical activity environment on weight loss treatment outcomes . It was hypothesized that behavioral weight loss program ( BWLP ) participants who received an additional MI would evidence superior weight loss maintenance compared to participants who received a BWLP alone ( no contact [ NC ] ) . Fifty-one obese adults were r and omly assigned to participate in a 16-week weight loss intervention followed by NC or a 6-week MI . Thirty-eight participants completed the six-month follow-up . Body weight , percent body fat , cardiorespiratory fitness , self-reported physical activity , and self-reported diet ( i.e. , calories , percent daily intake of fat , protein , and carbohydrates ) were assessed . Participants significantly decreased their weight , increased physical activity/fitness , and improved dietary intake ( ps<.05 ) . MI participants had significantly greater weight loss maintenance than NC participants ( ps<.05 ) . Helping obese individuals to modify their personal eating and physical activity environment in order to reduce exposure to " obesogenic " cues may contribute to long-term weight loss maintenance Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE To examine the efficacy of a lifestyle modification programme in weight maintenance for obese subjects after cessation of treatment with Orlistat . METHODS Fifty-five subjects with and without diabetes mellitus were r and omized to a lifestyle modification programme or to usual care at the end of 6 months ' treatment with Orlistat . The intervention programme was nutritionist led , consisting of components of dietary management , physical activity , peer group support and discussion using techniques of self-monitoring , stimulus control and cognitive restructuring . Anthropometric indices , body composition , basal metabolic rate , blood pressure , fasting glucose , glycosylated haemoglobin , lipid profile , 24-hour urinary albumin excretion , dietary intake , physical activity level , and quality of life were assessed before and after the intervention period . Results Subjects in the intervention group maintained their weight loss and favourable anthropometric , metabolic , dietary intake , physical activity and quality of life profiles , while most parameters deteriorated in the usual care group , being more marked in subjects with diabetes . The magnitude of weight gain was comparable to that lost during Orlistat treatment . CONCLUSION A specially design ed nutritionist-led lifestyle modification programme for obese subjects is effective in weight maintenance after treatment with Orlistat , in the absence of which the benefits of drug treatment were lost . The magnitude of the effect of lifestyle modification is comparable to that observed with Orlistat BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVE To compare weight loss in blacks and whites in the Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) . RESEARCH METHODS AND PROCEDURES TONE enrolled 421 overweight white and 164 overweight black adults , 60 to 79 years old , with blood pressure well-controlled on a single , antihypertensive drug . Drug therapy withdrawal was attempted 3 months after r and omization to counseling for weight loss , sodium reduction , both weight loss and sodium reduction , or to usual care , with follow-up for 15 to 36 months after enrollment . Statistical procedures included repeated measures analysis of covariance and logistic and proportional hazards regression . RESULTS In the weight-loss condition , net weight change ( in kilograms ) was -2.7 in blacks and -5.9 in whites ( p < 0.001 ; ethnic difference , p = 0.0002 ) at 6 months and -2.0 ( p < 0.05 ) in blacks and -4.9 ( p < 0.001 ) in whites at the end of follow-up ( ethnic difference , p = 0.007 ) . In weight/sodium , net weight change was -2.1 ( p < 0.01 ) in blacks and -2.8 ( p < 0.001 ) in whites at 6 months , and -1.9 in blacks and -1.7 in whites at the end of follow-up ( p < 0.05 ; ethnic difference , p > 0.5 ) . Exploratory analyses suggested a more favorable pattern of weight change in blacks than in whites from 6 months onward . There was no ethnic difference in blood pressure outcomes . DISCUSSION Whites lost more weight than blacks without , but not with , a concurrent focus on sodium reduction BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin Tested whether the efficacy of behavior therapy for obesity might be improved by the programmatic additions of an aerobic exercise regimen during treatment and a multicomponent maintenance program following treatment . 14 male and 76 female obese 22–60 yr olds were r and omly assigned to 2 treatment conditions ( behavior therapy or behavior therapy plus aerobic exercise ) and 2 posttreatment conditions ( no further contact or a multicomponent maintenance program ) . The exercise regimen consisted of 80 min/week of brisk walking or stationary cycling . The maintenance program included therapist contact by telephone and mail and peer self-help group meetings . At posttreatment , Ss in the behavior therapy plus aerobic exercise condition lost significantly more weight than those who received behavior therapy only . Over an 18-mo follow-up period , maintenance program participants demonstrated significantly better weight-loss progress than Ss in the no-further-contact condition CONTEXT Behavioral weight loss interventions achieve short-term success , but re-gain is common . OBJECTIVE To compare 2 weight loss maintenance interventions with a self-directed control group . DESIGN , SETTING , AND PARTICIPANTS Two-phase trial in which 1032 overweight or obese adults ( 38 % African American , 63 % women ) with hypertension , dyslipidemia , or both who had lost at least 4 kg during a 6-month weight loss program ( phase 1 ) were r and omized to a weight-loss maintenance intervention ( phase 2 ) . Enrollment at 4 academic centers occurred August 2003-July 2004 and r and omization , February-December 2004 . Data collection was completed in June 2007 . INTERVENTIONS After the phase 1 weight-loss program , participants were r and omized to one of the following groups for 30 months : monthly personal contact , unlimited access to an interactive technology-based intervention , or self-directed control . Main Outcome Changes in weight from r and omization . RESULTS Mean entry weight was 96.7 kg . During the initial 6-month program , mean weight loss was 8.5 kg . After r and omization , weight regain occurred . Participants in the personal-contact group regained less weight ( 4.0 kg ) than those in the self-directed group ( 5.5 kg ; mean difference at 30 months , -1.5 kg ; 95 % confidence interval [ CI ] , -2.4 to -0.6 kg ; P = .001 ) . At 30 months , weight regain did not differ between the interactive technology-based ( 5.2 kg ) and self-directed groups ( 5.5 kg ; mean difference -0.3 kg ; 95 % CI , -1.2 to 0.6 kg ; P = .51 ) ; however , weight regain was lower in the interactive technology-based than in the self-directed group at 18 months ( mean difference , -1.1 kg ; 95 % CI , -1.9 to -0.4 kg ; P = .003 ) and at 24 months ( mean difference , -0.9 kg ; 95 % CI , -1.7 to -0.02 kg ; P = .04 ) . At 30 months , the difference between the personal-contact and interactive technology-based group was -1.2 kg ( 95 % CI -2.1 to -0.3 ; P = .008 ) . Effects did not differ significantly by sex , race , age , and body mass index subgroups . Overall , 71 % of study participants remained below entry weight . CONCLUSIONS The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level . Monthly brief personal contact provided modest benefit in sustaining weight loss , whereas an interactive technology-based intervention provided early but transient benefit . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00054925 This study evaluated the effectiveness of two posttreatment programs design ed to enhance the maintenance of weight loss . Eighty-five obese clients were r and omly assigned to either ( a ) behavior therapy plus a peer-support maintenance program , ( b ) behavior therapy plus a therapist-contact maintenance program , or ( c ) behavior therapy only . At a 7-month follow-up session , the therapist-contact program result ed in significantly greater maintenance of weight loss compared with the peer support and behavior therapy only conditions . However , by the time of an 18-month follow-up assessment , overall relapse rates were equivalent across conditions This study evaluated the effectiveness of four posttreatment programs design ed to enhance the long-term maintenance of weight loss . Mildly and moderately obese adults ( N = 123 ) were r and omly assigned to one of the following five conditions : ( a ) behavior therapy only ; ( b ) behavior therapy plus a posttreatment therapist-contact maintenance program ; ( c ) behavior therapy plus posttreatment therapist contact plus a social influence maintenance program ; ( d ) behavior therapy plus posttreatment therapist contact plus an aerobic exercise maintenance program ; or ( e ) behavior therapy plus posttreatment therapist contact plus both the aerobic exercise and social influence maintenance programs . All posttreatment programs were conducted in 26 biweekly sessions during the year following behavioral treatment for obesity . At an 18-month follow-up evaluation , all four conditions that combined behavior therapy with a posttreatment maintenance program yielded significantly greater long-term weight losses than behavior therapy alone OBJECTIVE The purpose of this study was to compare weight regain in a group of perimenopausal women ( 48.0+/-4.4 years old ) , r and omized to a 12-month weight maintenance Internet intervention or to self-directed weight maintenance after a 4-month weight loss treatment . METHODS AND PROCEDURES After a 4-month behavioral weight loss program , 135 women were r and omized to either Internet or self-directed groups . The Internet group ( n=66 ) used a website to gain information and complete logs concerning their weight , diet , and exercise progress over a 12-month follow-up . The 69 self-directed women had no contact with study staff . All women were measured for weight and body composition , and diet intake , and were interviewed using the 7-day physical activity question naires at baseline , 4 months , and 16 months . RESULTS At the end of the 12-month follow-up , the Internet and self-directed groups had regained on average 0.4+/-5.0 kg and 0.6+/-4.0 kg , respectively ( P=0.5 ) . In within-group analyses , Internet diet-log entries were correlated with follow-up weight change ( r=-0.29 ; P<0.05 ) and moderately with change in exercise energy expenditure ( EEE ; r=0.44 ; P<0.01 ) . Follow-up weight change was not correlated with change in dietary intake . DISCUSSION While significant weight loss was maintained over follow-up by both groups of women , Internet use did not surpass self-direction in helping to sustain weight loss . Among Internet users , Internet use was related to weight change and EEE |
2,118 | 16,915,379 | Although tryptophan depletion reduced plasma serotonin levels in all studies , significant effects on mood were only observed in studies with recovered depressed patients .
In functional neuroimaging studies ATD was consistently found to modulate cortical activity in prefrontal areas implicated in mnemonic and executive functions and in orbitofrontal , cingulate , and subcortical regions associated with emotional processing .
Electrophysiological studies indicated that ATD has a significant effect on both “ selective ” and “ involuntary ” attention .
Conclusions The combination of ATD with modern brain imaging techniques allows the investigation of the neurophysiological effects of reduced 5-HT synthesis on global brain activity , executive functions , memory , attention , and affect | Rationale There is a growing psychopharmacological literature on the use of Acute Tryptophan Depletion ( ATD ) for experimental modulation of the serotonergic system .
To date , no systematic review has been undertaken assessing the neurophysiological effects following this acute central 5-HT manipulation . | Rationale Serotonin is shown to regulate the activity of primary auditory cortex , but little is known about serotonin modulation of other sensory cortices . Methods We investigated somatosensory evoked magnetic fields ( SEF ) to left median nerve stimulation in eight healthy subjects in a double-blind , controlled , cross-over design study after acute tryptophan depletion ( ATD ) and control mixture . SEFs were recorded with the whole-head magnetoencephalography 6 h after ingestion of mixtures . The SEF sources and strength were estimated by a least-squares fit of a single equivalent current dipole . Results ATD decreased the total and free TPR levels by 75 and 48 % and control mixture increased them by 98 % and 44 % . ATD had no effect on the amplitudes or latencies of SEF components . The source locations of the responses were not significantly affected by ATD . ConclusionS erotonin does not affect stimuli processing in the primary somatosensory cortex Abstract Serotonin ( 5-hydroxytryptamine ; 5-HT ) circuits may play a role in cognitive performance , particularly in learning and memory . Cognitive impairment is often seen in depressed patients , in whom 5-HT turnover in the brain is thought to be lowered . A possible human pharmacological model to study the involvement of the serotonergic system in cognitive impairment is to reduce central 5-HT synthesis through L-tryptophan depletion in healthy subjects . In this study , the cognitive effects of tryptophan depletion were assessed and whether genetically or developmentally determined vulnerability factors were predictive of the cognitive impairment induced by tryptophan depletion . Sixteen healthy volunteers with a positive family history of depression and 11 without were given 100 g of an amino acid mixture with or without tryptophan , according to a double-blind , cross-over design . Tryptophan depletion specifically impaired long-term memory performance in all subjects : delayed recall performance , recognition sensitivity , and recognition reaction times were significantly impaired after tryptophan depletion relative to placebo . Short-term memory and perceptual and psychomotor functions were unchanged . There were no differences between groups with a positive and a negative family history for depression . On the basis of these results , it is concluded that tryptophan depletion specifically impairs long-term memory formation , presumably as a result of an acute decrease in 5-HT turnover in the brain Rationale and objective In animal and human studies , the neurotransmitter serotonin ( 5-hydroxytryptamine ; 5-HT ) has been implicated in mediating impulsiveness and aggression . To test the hypothesis that 5-HT modulates neuro-cognitive brain activation during inhibitory control , we examined the effect of acute tryptophan depletion ( ATD ) , a dietary challenge , which has been shown to decrease 5-HT synthesis in the brain , on functional brain activation during a go/no-go task . Methods Nine healthy , right-h and ed volunteers performed a rapid , event-related go/no-go task in two functional magnetic resonance imaging ( fMRI ) scanning sessions , 5 h after either a tryptophan-free or a balanced amino acid drink in a double-blind , sham depletion-controlled , counterbalanced , crossover design . The task required subjects to selectively execute or inhibit a motor response . Tryptophan depletion significantly lowered total plasma tryptophan concentration by 80 % , but did not significantly alter inhibitory performance or mood ratings . Results ATD significantly reduced right orbito-inferior prefrontal activation during the no-go condition , and increased activation in superior and medial temporal cortices . Conclusions These findings provide neuro-functional evidence of a serotonergic modulation of right inferior prefrontal during inhibitory motor control . The increased engagement of temporal brain regions may reflect compensatory mechanisms BACKGROUND The amygdala has a central role in processing emotions , particularly fear . During functional magnetic resonance imaging ( fMRI ) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces . METHODS We applied the masked faces paradigm to patients with major depression ( n = 11 ) and matched control subjects ( n = 11 ) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment . Data were analyzed using left and right amygdala a priori regions of interest , in an analysis of variance block analysis and r and om effects model . RESULTS Depressed patients had exaggerated left amygdala activation to all faces , greater for fearful faces . Right amygdala did not differ from control subjects . Following treatment , patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces . Control subjects had no differences between the two scanning sessions . CONCLUSIONS Depressed patients have left amygdala hyperarousal , even when processing stimuli outside conscious awareness . Increased amygdala activation normalizes with antidepressant treatment Involuntary attention shifting , i.e. , detecting and orienting to unexpected stimulus changes , may be altered at low brain serotonin ( 5-hydroxytryptamine ; 5-HT ) levels . This was studied in 13 healthy subjects ( 21 - 30 years old ; 6 females ) by using a dietary challenge , acute tryptophan depletion ( ATD ) , which decreases 5-HT synthesis in the brain . Five hours after ingestion of either ATD or control mixture ( r and omized , double-blinded , crossover design ) , brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography ( EEG ) and 122-channel magnetoencephalography ( MEG ) . During the measurement , the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly . Occasionally , the frequency of the tones changed ( 10 % increase/decrease ) , causing involuntary attention shifting . ATD significantly lowered plasma tryptophan concentrations ( total tryptophan decreased by 75 % , free tryptophan decreased by 35 % ) . As compared to the control condition , ATD reduced the amplitude of the deviant-tone N2 wave , including the overlapping mismatch negativity ( MMN ) and N2b subcomponents , which are suggested to reflect change detection in the brain . The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN . However , no ATD effects were observed in P3 to task-irrelevant frequency change . Reaction time ( RT ) to deviants per se was not significantly affected , but RT in trials succeeding the deviant-frequency tones was increased by ATD , which suggested impaired reorienting to the task-relevant activity . In conclusion , the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate re source allocation to the task-relevant activity To eluci date serotonin modulation of selective attention , 13 volunteers ( 21 - 30 years ) were studied in two sessions , 5 h after either acute tryptophan depletion ( ATD ) that decreases brain serotonin synthesis , or control-mixture ingestion ( r and omized , double-blind , cross-over design ) . Simultaneous electroencephalogram and magnetoencephalogram were measured during dichotic listening of two concurrent trains of st and ard and deviant tones . Subjects counted the deviants presented to one ear and ignored those presented to the other ear . ATD lowered plasma total tryptophan by 75 % and free tryptophan by 39 % . ATD suppressed the amplitude enhancement of P50 and N1 to selectively attended tones , but did not affect the later aspects of processing negativity . The P50 latencies were increased after ATD , irrespective of attention . In conclusion , serotonin may regulate attentional modulation of early cortical stimulus processing Several lines of evidence suggest that the auditory evoked potential ( AEP ) augmenting/reducing slope may serve as a biological marker of central serotonergic activity . According to Hegerl and Juckel ( Biol . Psychiatry , 33 , 1993 , 173 ) , reduced serotonergic activity is hypothesized to increase the slope of the AEP amplitude stimulus intensity function ( ASF-slope ) . Hints for this hypothesis were investigated by employing the acute tryptophan depletion paradigm in 18 healthy females . A within-subject , placebo controlled double-blind cross over design was used for that purpose . Subjects ingested both a 50 g amino-acid drink with ( placebo condition ) and without tryptophan ( depletion condition ) . With respect to the N1/P2-slope , test-retest reliability of a 1 week interval ranged between r=0.56 and 0.58 for the pre-ingestion baseline recording sessions . Affect was not altered by tryptophan depletion and not related to the ASF-slope . The comparison between placebo and depletion conditions did not reveal significant alterations of the ASF-slope , neither after 5 nor 6 h post-ingestion . Thus , the results do not support the assumption of the ASF-slope reflecting central serotonergic function Abstract Rationale . Intensity dependence of the N1/P2 components may be regulated by serotonergic neurons in the primary auditory cortex , where low activity leads to a high intensity dependence and vice versa . Depletion of tryptophan ( TRP ) , a precursor for serotonin has been described to reduce serotonin content in brain of animals and humans . Objective . We investigated the intensity dependence of magnetic and electric N1/P2 components in ten subjects in a double-blind , controlled , cross-over design study after oral mixture of amino-acids leading to acute tryptophan depletion ( ATD ) and control . Methods . Auditory evoked magnetic fields ( AEF ) and potentials ( AEP ) were recorded with 122-channel magnetoencephalography simultaneously with 64-channel EEG 5 h after ingestion of mixtures . The AEF sources and strength were estimated by a least-squares fit of a single equivalent current dipole . The amplitudes and latencies of N1 and P2 recorded with EEG were analyzed at frontal electrode site . Results . TRP depletion decreased the total and free TRP levels by 76 and 45 % and control mixture increased it by 48 and 28 % . ANOVA showed that ATD had a significant main effect on the N1m/P2 m dipole moments at the contralateral ( P=0.02 ) , but failed significantly to influence the ipsilateral responses . A significant mixture ingestion-by-stimulus intensity interaction was observed on the N1m/P2 m dipole moments at the contralateral hemisphere ( P=0.01 ) . The N1/P2 slope for intensity dependence function was decreased following ATD compared with the control experiment ( P=0.01 ) at the contralateral hemisphere . For EEG , a significant mixture ingestion-by-stimulus intensity interaction on the N1 latencies at the Fz electrode position was observed ( P=0.01 ) . Conclusion . ATD decreased the intensity dependence of N1m/P2 m source dipole moments in the primary auditory cortex at the hemisphere contralateral to the ear stimulated . These results suggest that serotonin participates in the regulation of intensity of auditory stimulation We studied the effects of acute tryptophan depletion ( ATD ) on early cortical auditory processing . Middle-latency auditory evoked fields ( MAEF ) were investigated in 14 healthy subjects after 5 h of ATD or control mixture ingestion in a r and omized , double-blinded , controlled cross-over design study . MAEFs to monaural click stimuli ( 0.1-ms duration ) were recorded with a 122-channel neuromagnetometer . Total plasma tryptophan ( Trp ) , free Trp , and large neutral amino acid ( LNAA ) concentrations were determined by using high-performance liquid chromatography . ATD lowered the total plasma Trp levels by 75 % , free Trp level by 47 % , and the ratio Trp/ΣLNAA by 92 % . The control mixture increased total Trp level by 45 % and free Trp by 32 % , and decreased the ratio Trp/ΣLNAA by 35 % . The ratio tyrosine/ΣLNAA did not differ between ATD and control experiment . ATD result ed in a significant main effect on Pam latencies and a near-significant main effect on Pam amplitudes . A significant Mixture ingestion X Sex interaction on Nbm amplitude and a significant Mixture ingestion X Sex X Hemisphere interaction on Pam latency were observed . ATD did not affect the MAEF source dipoles . The Pam latencies in both hemispheres had a significant negative relationship with the extent of ATD . The results suggest that the neurotransmitter serotonin is involved in early auditory cortical processing . Further , the serotonin modulation may be different in males and females Event-related functional magnetic resonance imaging was used to measure blood oxygenation level-dependent responses in 13 young healthy human volunteers during performance of a probabilistic reversal-learning task . The task allowed the separate investigation of the relearning of stimulus – reward associations and the reception of negative feedback . Significant signal change in the right ventrolateral prefrontal cortex was demonstrated on trials when subjects stopped responding to the previously relevant stimulus and shifted responding to the newly relevant stimulus . Significant signal change in the region of the ventral striatum was also observed on such reversal errors , from a region of interest analysis . The ventrolateral prefrontal cortex and ventral striatum were not significantly activated by the other , preceding reversal errors , or when subjects received negative feedback for correct responses . Moreover , the response on the final reversal error , before shifting , was not modulated by the number of preceding reversal errors , indicating that error-related activity does not simply accumulate in this network . The signal change in this ventral frontostriatal circuit is therefore associated with reversal learning and is uncontaminated by negative feedback . Overall , these data concur with findings in rodents and nonhuman primates of reversal-learning deficits after damage to ventral frontostriatal circuitry , and also support recent clinical findings using this task Normal male human subjects ingested amino acid mixtures which were tryptophan-free , balanced or contained excess tryptophan . The tryptophan-free mixture causes a marked depletion of plasma tryptophan by 5 h. At this time the subjects in the tryptophan-free group had significantly elevated scores on the depression scale of the Multiple Affect Adjective Checklist . The tryptophan-free group also performed worse than the other two groups in a proofreading task carried out while listening to a tape with themes of hopelessness and helplessness ( dysphoric distractor ) . Cognitive theories of depression predict greater distractability of depressed individuals by dysphoric themes . Thus , both measures indicate a rapid mood lowering effect of tryptophan depletion in normal males . This effect is probably mediated by a lowering of brain 5-hydroxytryptamine . Although the mood-lowering effect was not as great as that seen in depressed patients , our results suggest that low brain 5HT might be one factor precipitating depression in some patients Rationale : Neuropsychological impairments in depressive illness may be secondary to proposed serotonergic abnormalities . Acute tryptophan depletion ( ATD ) in healthy subjects impairs episodic memory , but the mechanism of this is unclear . Objectives : To examine the effects of ATD on the neural correlates of episodic memory retrieval in healthy subjects . Methods : Fourteen healthy men were given an amino acid cocktail drink with or without tryptophan , in a double blind , crossover design . Event related potentials ( ERPs ) were recorded during a well-vali date d episodic memory task performed 5 h after drink ingestion . Subjects listened to words spoken in a male or female voice . At test , old and new words were presented visually ; subjects judged whether words were old or new , and if old , the gender of the voice at study . Results : ATD led to an 84±5 % reduction in plasma free tryptophan concentrations , and significantly impaired episodic memory recall . ERP recordings demonstrated previously reported left parietal and right frontal " old/new " differences for ERPs to items associated with accurate episodic memory retrieval versus correctly rejected new items . ATD increased ERP voltage between 500 and 1400 ms post-stimulus particularly over posterior regions of the scalp , but there was no interaction with item type . Topographical analysis of the old/new difference revealed no significant treatment by site interaction . Conclusions : ATD impairs episodic memory recall with no effect on the magnitude or topography of the neural correlates of retrieval in healthy subjects . This suggests that the effects of ATD on recall may reflect an impairment of memory encoding and /or consolidation Abstract Rationale : The intensity dependence of the auditory evoked potentials ( AEP ) has been suggested to be a specific biological marker of central serotonergic activity . Objective : While previous studies used circumstantial evidence to support this hypothesis , we manipulated ( decreased ) cerebral levels of serotonin directly by using tryptophan depletion . Methods : Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions . AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature . Results : For none of the mixtures a significant effect of tryptophan depletion was found . There was a trend towards reduced intensity dependency after tryptophan depletion , especially in the right hemisphere . This reduction correlated with the amount of reduced tryptophan in plasma . Conclusions : The results indicate , in contrast to earlier indirect studies , that the intensity dependence of AEPs is not a specific marker of central serotonergic activity Abstract Rationale : Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking . However , little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour . Objectives and methods : We compared the effects of rapid plasma tryptophan depletion , acute doses of the mixed indirect catecholamine agonist , methylpheni date ( 40 mg ) , and acute doses of the α1/α2 agonist , clonidine ( 1.5 µg/kg ) , on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations ( i.e. updating the affective valence of exteroceptive stimuli ) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions . Results : Relative to subjects who received placebo , subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations , but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension . By contrast , subjects who received methylpheni date were able to learn effectively about changing stimulus-reward associations , but showed an enhanced ability to shift an attentional bias , in combination with slowed response times . Subjects who received clonidine showed neither of these changes . Conclusions : These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions ( e.g. orbitofrontal cortex , striatum and anterior temporal structures ) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value . On the other h and , facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment , perhaps through altered modulation of the dorsolateral prefrontal cortex . The implication s of these results for underst and ing the differential neuromodulation of cognitive functions are discussed The tryptophan depletion test is a research strategy to investigate the functional consequences of decreasing the brain serotonin metabolism . Because serotonin is involved in sleep regulation and the regulation of affective states , we studied the acute polysomnographic effects of tryptophan depletion and expected to induce similar changes of sleep EEG as observed in depressed patients . A total of 12 healthy subjects ( mean age 34 ± 3 years ) had eight polysomnograms , divided in two blocks of 4 consecutive nights . After one adaptation and 1 baseline night , subjects received a low-protein diet on day 3 and 4 until midday . On day 4 at 18.00 h , they drank an amino acid mixture either devoid of tryptophan or containing 2.3 g of tryptophan ( placebo control ) in r and omized and double-blind order , result ing in an 85 % decrease ( tryptophan depletion ) and a 144 % increase ( placebo control ) of serum tryptophan at 22.00 h. After tryptophan depletion but not placebo , significant effects on sleep EEG were observed in terms of decreased non-rapid eye movement ( non-REM ) stage 2 , increase of wake % , and of rapid eye movement ( REM ) density compared with baseline . REM latency was not altered , however the first and second REM period interval were significantly shorter after tryptophan depletion . This study underlines the impact of the serotonergic system on sleep maintenance and on REM sleep . © 1998 American College of BACKGROUND Efforts to model putative serotonergic deficits associated with affective disorders have frequently involved acute tryptophan depletion ( ATD ) as a manipulation strategy aim ed at lowering brain serotonin synthesis . In an attempt to widen the scope of the measurement probes used in these investigations , the central actions of ATD and a subsequent dose of fenfluramine were examined via utilization of quantitative electroencephalography ( EEG ) and mood ratings . METHODS Electroencephalograms ( EEG ) and subjective mood ratings were assessed in 28 healthy men before and after double-blind ingestion of a tryptophan-depleting ( T- ) amino acid mixture , or a nutritionally balanced ( B ) amino acid mixture containing tryptophan , and again after a single-blind oral dose of D , L-fenfluramine hydrochloride ( 60 mg ) . RESULTS Compared to the B mixture , the T- mixture reduced total plasma tryptophan by more than 75 % 5 hours after ingestion . Tryptophan depletion was associated with a modest lowering of mood and a slowing of EEG as indicated by increases in delta amplitude . Fenfluramine caused no change in mood but increased fast wave ( beta ) activity in anterior recordings when administered after the T- , but not after the B mixture . CONCLUSIONS Quantitative EEG measurements may be a promising method for study ing the central mechanisms underlying serotonin-mediated changes in mood and behavior Serotonin ( 5-HT , 5-hydroxytryptamine ) may have an important role in the maintenance of normal neuropsychological functioning . The method of acute tryptophan depletion ( ATD ) provides a pharmacological challenge by which central 5-HT levels can be temporarily decreased and effects on learning , memory and mood examined . Twenty healthy male volunteers were recruited to take part in this within-subject , double-blind , crossover study . Neuropsychological function was evaluated 4 - 6 h after ingestion of a control or 52 g tryptophan ( TRP ) depleting amino-acid drink . ATD significantly lowered levels of plasma total and free TRP ( p < 0.001 ) , but this did not affect mood or performance on tests of verbal and visuo-spatial learning and memory , attention or executive function . These results contradict previous findings ; however , the degree of disruption of central 5-HT levels result ing from the use of the 52 g amino-acid protocol may be an important factor in explaining the lack of effect . By utilizing more specific probes of individual 5-HT receptor subtypes , future studies can fully explore the role of 5-HT in neuropsychological functioning and may eluci date the factors determining vulnerability to the effects of serotonergic dysfunction We investigated the role of serotonin in cognitive activation of the frontal cortex . The serotonergic system was affected by the administration of an amino acids mixture without tryptophan ( tryptophan depletion ) . In a placebo-controlled double-blind cross-over study with 20 healthy volunteers , we tested the hypothesis that a tryptophan ( serotonin ) decrease affects the activation of prefrontal cortex by the Stroop test . Cognitive brain activation was evaluated by functional magnetic resonance imaging ( fMRI ) . Tryptophan depletion decreased the plasma tryptophan level up to 90 % for five hours after the tryptophan-free drink had been consumed when compared with the same mixture with tryptophan ( p?0.0001 ) . Tryptophan depletion did not affect the Stroop test performance . We compared fMRI activation in both conditions ( tryptophan depletion and placebo ) with plasma tryptophan levels as the covariates . The tryptophan depletion increased the activation ( fMRI signal ) in the bilateral mediofrontal cortex , anterior cingulate and left dorsolateral prefrontal cortex . The present findings allow the postulate that serotonergic medial forebrain and cingulum bundle pathways play a role in the activity of cortical structures involved in Stroop test processing Decreasing brain 5-HT levels by acute tryptophan depletion has been shown to selectively impair cognition in healthy volunteers . In bipolar disorder , ATD causes measurable neurophysiological effects without altering mood . The purpose of this study was to examine the effects of ATD on neuropsychological performance in 14 euthymic bipolar patients . Cognitive function was evaluated 4 - 6 h after ingestion of a control or depleting amino-acid drink . Plasma tryptophan levels fell significantly following the depleting drink , however there were no main effects on the ID/ED set-shift task , Paired Associates Learning or Vigil . A trend towards a decrease in the proportion of perfect solutions on the Tower of London task was observed when depleted . While ATD reduces 5-HT levels in the brain , it does not appear to alter neuropsychological performance on tests of sustained attention or associative learning . Effects on specific ' executive ' functions are less clear , and should be the focus for future research Short latency evoked potentials were recorded during a cross-modal selective attention task to evaluate recent proposals that sensory transmission in the peripheral auditory and visual pathways can be modified selectively by centrifugal mechanisms in humans . Twenty young adult subjects attended in turn to either left-ear tones or right-field flashes presented in a r and omized sequence , in order to detect infrequent , lower-intensity targets . Attention-related enhancement of longer-latency components , including the visual P105 and the auditory N1/Nd waves and T-complex , showed that subjects were able to adopt a selective sensory set toward either modality . Neither the auditory evoked brainstem potentials nor the early visual components ( electroretinogram , occipito-temporal N40 , P50 , N70 waves ) were significantly affected by attention . Measures of retinal B-waves were significantly reduced in amplitude when attention was directed to the flashes , but concurrent recordings of eyelid electromyographic activity and the electro-oculogram indicated that this effect may have result ed from contamination of the retinal recordings by blink microreflex activity . A trend toward greater positivity in the 15 - 50 ms latency range for auditory evoked potentials to attended tones was observed . These results provide further evidence that the earliest levels of sensory transmission are unaffected by cross-modal selective attention , but that longer latency exogenous and endogenous potentials are enhanced to stimuli in the attended modality BACKGROUND 5-HT modulates electroencephalographic ( EEG ) activity , which is abnormal in bipolar disorder and EEG abnormalities persist in euthymic bipolar patients . The EEG may therefore be a sensitive marker of 5-HT function in bipolar disorder . We examined the effects of acute tryptophan depletion ( ATD ) on EEG activity in bipolar patients . METHODS Fourteen patients with DSM IV Bipolar 1 disorder participated in a within-subject , double-blind , placebo-controlled , r and om-order crossover study . Following ATD quantitative power spectrum brain mapping and measurement of auditory evoked potentials were carried out . RESULTS ATD produced a significant fall in the amplitude of N1P2 and P300 components of the auditory evoked potential , but no significant changes in the power spectrum . There was an 83 % reduction in plasma tryptophan after the depleting but not the control drink . LIMITATIONS The effect of ATD on brain 5-HT levels was not directly measured . The number of patients is relatively small . The control condition may alter these electrophysiological measures . CONCLUSIONS ATD attenuates auditory evoked potentials in bipolar disorder with the distribution of this effect being towards the front of the brain . These changes are not related to any change in mood . This is a potential trait marker of bipolar disorder , however there needs to be further exploration of this paradigm in controls and other patient groups Background Serotonin is known to modulate cognitive functioning and has been implicated in the cognitive deficits associated with affective disorders . The present study examined regional brain activation during two tasks that are known to engage the pre-frontal cortex and are performed poorly by patients with depression and bipolar disorder . We tested the hypothesis that acute tryptophan depletion ( ATD ) would attenuate pre-frontal activation during both tasks . Material s and methods Ten healthy right-h and ed volunteers were studied using functional MRI whilst performing a 2-back verbal working memory task and a phonological verbal fluency task . Subjects were studied in two separate sessions , after either a tryptophan-free or a balanced amino acid drink , in a double-blind design . Task performance and mood were measured online . Results Relative to sham depletion , ATD attenuated activation in the right superior frontal gyrus during the 2-back task and in the medial frontal gyrus and precuneus during the verbal fluency task . ATD lowered total plasma tryptophan by 79 % but had no significant effect on either task performance or mood . Conclusions The engagement of pre-frontal cortex during verbal working memory and verbal fluency tasks is significantly modulated by central serotonergic activity . The different location of these modulatory effects within the frontal cortex may reflect the engagement of distinct cognitive processes by the respective tasks CONTEXT An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder ( MDD ) is the response to tryptophan depletion ( TD ) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan . OBJECTIVE To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD . DESIGN R and omized double-blind crossover study . SETTING Outpatient clinic . PARTICIPANTS Twenty-seven medication-free patients with remitted MDD ( 18 women and 9 men ; mean + /- SD age , 39.8 + /- 12.7 years ) and 19 controls ( 10 women and 9 men ; mean + /- SD age , 34.4 + /- 11.5 years ) . INTERVENTIONS We induced TD by administering capsules containing an amino acid mixture without tryptophan . Sham depletion used identical capsules containing hydrous lactose . Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD . Magnetic resonance images were obtained for all participants . MAIN OUTCOME MEASURES Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD . Behavioral assessment s used a modified ( 24-item ) version of the Hamilton Depression Rating Scale . RESULTS Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls ( P<.001 ) . Compared with sham depletion , TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex , medial thalamus , anterior and posterior cingulate cortices , and ventral striatum in patients with remitted MDD but not in controls . CONCLUSION The pattern of TD-induced regional cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific , serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD Abstract Rationale . Cognitive impairment is a common feature of depressive illness . While accumulating evidence suggests that brain serotonin ( 5-HT ) pathways play an important role in the neurobiology of depression , the extent to which altered 5-HT function is responsible for the associated changes in cognition and emotion remains unclear . Objective . The present study examined the effects of acute dietary depletion of tryptophan ( TRP ) on cognitive and affective processing in healthy volunteers and explored the putative role of 5-HT in the neuropsychology of depression . Methods . We administered computerised cognitive tests to healthy control participants following ingestion of TRP-free and nutritionally balanced amino acid drinks in a double-blind , placebo-controlled , crossover design . Results . The TRP-free amino acid mixture significantly lowered plasma total and free TRP concentrations relative to baseline values and produced selective deficits similar to those observed previously in cases of clinical depression . In particular , TRP depletion increased response times for happy but not sad targets in an affective go/no-go task and slowed responding in a visual discrimination and reversal learning task . These deficits were not due to a global sedative effect , as planning ability was unimpaired . Conclusions . The present data indicate that serotonergic factors may be more involved in the disrupted inhibitory and emotional processing characteristic of depression than in other aspects of executive function , such as planning ability . These findings support the recent proposal that serotonergic manipulation may have greater effects on tasks mediated by frontal circuitry that includes the orbitofrontal cortex than by dorsolateral prefrontal cortex circuitry This study used functional magnetic resonance imaging to examine the effects of acute tryptophan ( TRP ) depletion ( ATD ) , a well-recognized method for inducing transient cerebral serotonin depletion , on brain activity during probabilistic reversal learning . Twelve healthy male volunteers received a TRP-depleting drink or a balanced amino-acid drink ( placebo ) in a double-blind crossover design . At 5 h after drink ingestion , subjects were scanned while performing a probabilistic reversal learning task and while viewing a flashing checkerboard . The probabilistic reversal learning task enabled the separate examination of the effects of ATD on behavioral reversal following negative feedback and negative feedback per se that was not followed by behavioral adaptation . Consistent with previous findings , behavioral reversal was accompanied by significant signal change in the right ventrolateral prefrontal cortex ( PFC ) and the dorsomedial prefrontal cortex . ATD enhanced reversal-related signal change in the dorsomedial PFC , but did not modulate the ventrolateral PFC response . The ATD-induced signal change in the dorsomedial PFC during behavioral reversal learning extended to trials where subjects received negative feedback but did not change their behavior . These data suggest that ATD affects reversal learning and the processing of aversive signals by modulation of the dorsomedial PFC |
2,119 | 22,340,636 | Existing school-based prevention programs have shown to be efficacious in the Australian context .
The findings challenge the commonly held view that school-based prevention programs are not effective | ISSUES To reduce the occurrence and costs related to substance use and associated harms it is important to intervene early .
Although a number of international school-based prevention programs exist , the majority show minimal effects in reducing drug use and related harms .
Given the emphasis on early intervention and prevention in Australia , it is timely to review the programs currently trialled in Australian schools .
This paper reports the type and efficacy of Australian school-based prevention programs for alcohol and other drugs . | The Life Education organization offers a drug education programme to an estimated one million Australian primary schoolchildren . It is believed the programme delays experimentation with or initiation into smoking , alcohol use and the taking of analgesics . This study examined the short-term public health effects on 3000 11- and 12-year-old students , of whom 1700 were exposed to 5 consecutive years of the programme . The other 1300 students were not exposed to the programme . After controlling for the known predictors of social drug use there was no evidence that Life Education students , when compared with students receiving conventional school-based drug education , were less likely to have smoked , were less likely to have drunk or were less likely to have used analgesics . Indeed , the evidence suggested that Life Education-students were slightly more likely to use these substances , and that the programme had different effects on boys ' and girls ' drug use . Given that these findings are consistent with previous research evaluating similar drug education programmes , it is hypothesized they are most likely to do with the design of the programme itself Objective : The aim of the present study was to conduct a cross-validation trial of the efficacy of a computerized school-based intervention for alcohol misuse in adolescents . Method : A cluster r and omized control trial was carried out . Intervention and control groups were assessed at baseline , immediately after and 6 months after the intervention . A total of 764 Year 8 students from 10 independent secondary schools in Sydney , Australia participated in the study . Half of the schools were r and omly allocated to the computerized prevention programme ( n=397 ) , and half to their usual classes ( n=367 ) . The six-lesson computerized intervention was evidence and curriculum based while having a focus on harm-minimization . Knowledge , expectancies , alcohol consumption ( frequency , quantity and binging ) , patterns of use , and harms associated with one 's own use of alcohol were assessed . Results : There were significant improvements in knowledge regarding alcohol use at immediate and 6 month follow up . Average weekly alcohol consumption was reduced immediately after the intervention . No differences between groups were found on alcohol expectancies , frequency of drinking to excess and harms related to alcohol use over time . Conclusions : The present results support the Climate Management and Treatment Education ( CLIMATE ) Schools : alcohol module as an effective intervention in increasing alcohol knowledge and reducing alcohol use in the short term AIMS The School Health and Alcohol Harm Reduction Project ( SHAHRP study ) aim ed to reduce alcohol-related harm in secondary school students . DESIGN The study used a quasi-experimental research design in which r and omly selected and allocated intervention and comparison groups were assessed at eight , 20 and 32 months after baseline . SETTING Metropolitan , government secondary schools in Perth , Western Australia . PARTICIPANTS The sample involved over 2300 students . The retention rate was 75.9 % over 32 months . INTERVENTION The evidence -based intervention , a curriculum programme with an explicit harm minimization goal , was conducted in two phases over a 2-year period . MEASURES Knowledge , attitude , total alcohol consumption , risky consumption , context of use , harm associated with own use and harm associated with other people 's use of alcohol . FINDINGS There were significant knowledge , attitude and behavioural effects early in the study , some of which were maintained for the duration of the study . The intervention group had significantly greater knowledge during the programme phases , and significantly safer alcohol-related attitudes to final follow-up , but both scores were converging by 32 months . Intervention students were significantly more likely to be non-drinkers or supervised drinkers than were comparison students . During the first and second programme phases , intervention students consumed 31.4 % and 31.7 % less alcohol . Differences were converging 17 months after programme delivery . Intervention students were 25.7 % , 33.8 % and 4.2 % less likely to drink to risky levels from first follow-up onwards . The intervention reduced the harm that young people reported associated with their own use of alcohol , with intervention students experiencing 32.7 % , 16.7 % and 22.9 % less harm from first follow-up onwards . There was no impact on the harm that students reported from other people 's use of alcohol . CONCLUSIONS The results of this study support the use of harm reduction goals and classroom approaches in school drug education AIMS To determine the impact of a school-based harm minimization smoking intervention compared to traditional abstinence-based approaches . DESIGN , SETTING AND PARTICIPANTS A school-based cluster r and omized trial was conducted in Perth , Western Australia in 30 government high schools from 1999 to 2000 . Over 4000 students were recruited to participate and schools were assigned r and omly to either the harm minimization intervention or a st and ard abstinence-based programme . INTERVENTION The harm minimization intervention comprised eight 1-hour lessons over 2 years , quitting support from school nurses and enactment of policies to support programme components . Comparison schools implemented st and ard abstinence-based programmes and policies . MEASURES Cigarette smoking was categorized at two levels : regular smoking , defined as smoking on 4 or more days in the previous week ; and 30-day smoking as any smoking within the previous month . FINDINGS At immediate post-test ( 20 months post-baseline ) , after accounting for baseline differences , school-level clustering effects , socio-economic status , gender and family smoking , intervention students were less likely to smoke regularly [ OR = 0.51 , 95 % confidence interval ( CI ) = 0.36 , 0.71 ] or to have smoked within the previous 30 days ( OR = 0.69 , 95 % CI = 0.53 , 0.91 ) . CONCLUSION The school-based adolescent harm minimization intervention appears to have been more effective than the abstinence-based social influences programme at reducing regular smoking CONTEXT Selective interventions targeting personality risk are showing promise in the prevention of problematic drinking behavior , but their effect on illicit drug use has yet to be evaluated . OBJECTIVE To investigate the efficacy of targeted coping skills interventions on illicit drug use in adolescents with personality risk factors for substance misuse . DESIGN R and omized controlled trial . SETTING Secondary schools in London , United Kingdom . PARTICIPANTS A total of 5302 students were screened to identify 2028 students aged 13 to 16 years with elevated scores on self-report measures of hopelessness , anxiety sensitivity , impulsivity , and sensation seeking . Seven hundred thirty-two students provided parental consent to participate in this trial . INTERVENTION Participants were r and omly assigned to a control no-intervention condition or a 2-session group coping skills intervention targeting 1 of 4 personality profiles . MAIN OUTCOME MEASURES The trial was design ed and powered to primarily evaluate the effect of the intervention on the onset , prevalence , and frequency of illicit drug use over a 2-year period . RESULTS Intent-to-treat repeated- measures analyses on continuous measures of drug use revealed time x intervention effects on the number of drugs used ( P < .01 ) and drug use frequency ( P < .05 ) , whereby the control group showed significant growth in the number of drugs used as well as more frequent drug use over the 2-year period relative to the intervention group . Survival analysis using logistic regression revealed that the intervention was associated with reduced odds of taking up the use of marijuana ( beta = -0.3 ; robust SE = 0.2 ; P = .09 ; odds ratio = 0.7 ; 95 % confidence interval , 0.5 - 1.0 ) , cocaine ( beta = -1.4 ; robust SE = 0.4 ; P < .001 ; odds ratio = 0.2 ; 95 % confidence interval , 0.1 - 0.5 ) , and other drugs ( beta = -0.7 ; robust SE = 0.3 ; P = .03 ; odds ratio = 0.5 ; 95 % confidence interval , 0.3 - 0.9 ) over the 24-month period . CONCLUSION This study extends the evidence that brief , personality-targeted interventions can prevent the onset and escalation of substance misuse in high-risk adolescents . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00344474 This study examined the impact of a school-based preventive intervention on cannabis use in adolescence , using a cluster-r and omized trial of a multilevel intervention aim ed at improving social relationships within schools by promoting change in school environment . Four waves of data were collected at baseline ( 1997 , Year 8 : mean age 13 years ) and six , 18 , and 30 months later ( 1999 , Year 10 : mean age 16 years ) . Self-reported substance use , school engagement , and sociodemographic data were collected using computer-administered question naires . Some 2.678(74 % ) Year 8 students participated ( wave 1 ) with minimal attrition ( 10 % by wave 4 ) . Adjusting for baseline use , weak evidence existed for an intervention effect on the prevalence of any use at Year 10 ( OR 0.75 , 95 % CI 0.54 , 1.05 ) and incident weekly use ( OR 0.72 , 95 % CI 0.39 , 1.33 ) . These effects were reduced after adjusting for confounders . Moderate evidence suggested an interaction effect between intervention group and tobacco use ( p = 0.04 ) , suggesting the intervention was more effective for non-smokers at baseline ( Adj . OR 0.50 , 95 % CI 0.26 , 0.98 ) . This study indicates that a multi-level school-based program may provide an innovative direction for sustainable school interventions with the potential to reduce substance use INTRODUCTION AND AIMS This study aim ed to examine : ( a ) the influence of family factors relative to school , peer and individual influences on the development of adolescent alcohol use during the first year of secondary school ; and ( b ) the feasibility of preventing adolescent alcohol use by modifying family factors . DESIGN AND METHODS Twenty-four schools in Melbourne , Australia were r and omly assigned to either the ' Resilient Families ' intervention or a control condition . A baseline cohort of 2315 grade 7 students ( mean age 12.3 years ) were followed-up one year later ( n=2128 for longitudinal analyses ) . A sub-set of parents ( n=1166 ) also returned baseline surveys . RESULTS The prevalence of lifetime alcohol use in year 7 was 33 % and rose to 47 % by year 8 . Student-reported predictors of year 8 alcohol use included baseline alcohol [ Odds Ratio ( OR ) 3.64 ] and tobacco use ( 2.68 ) , and school friend 's alcohol ( 1.41 ) and tobacco use ( 1.64 ) . After adjusting for other influences , student-reported family factors were not maintained as significant predictors of year 8 alcohol use . Parent-report predictors of student-reported alcohol use included allowing alcohol use in the home ( 2.55 ) , parental alcohol use ( 1.88 ) and child hyperactivity ( 1.85 ) . Protective factors included attendance at brief parent education ( 0.60 ) and parent involvement in school education ( 0.65 ) . DISCUSSION AND CONCLUSIONS The intervention appeared to benefit education-related outcomes , but no overall effect in reducing student alcohol use was found in year 8 . Intervention effects on alcohol misuse may become significant in later secondary school once the entire program has been implemented . Considerable alcohol use was detected in early secondary school , suggesting that interventions to reduce alcohol use may be usefully implemented prior to this period AIMS Hazardous alcohol use is a leading cause of death among adolescents and young adults world-wide , yet few effective prevention interventions exist . This study was the first to examine a computerized harm minimization intervention to reduce alcohol misuse and related harms in adolescents . DESIGN Cluster r and omized controlled trial of a six-session curriculum-integrated harm minimization prevention program . The intervention was delivered by computer in the form of a teenage drama , which provided education through alcohol-related scenarios to which young people could relate . SETTING Schools in Australia . PARTICIPANTS A total of 1466 year 8 students ( 13 years ) from 16 high schools in Australia were allocated r and omly to a computerized prevention program ( n = 611 , eight schools ) or usual classes ( n = 855 , eight schools ) . MEASUREMENTS Change in knowledge , alcohol use , alcohol-related harms and alcohol expectancies . FINDINGS A computerized prevention program was more effective than usual classes in increasing alcohol-related knowledge of facts that would inform safer drinking choices and decreasing the positive social expectations which students believed alcohol may afford . For females it was effective in decreasing average alcohol consumption , alcohol-related harms and the frequency of drinking to excess ( more than four st and ard drinks ; 10 g ethanol ) . For males the behavioural effects were not significant . CONCLUSIONS A harm minimization approach is effective in educating young people about alcohol-related risks and is effective in reducing risky drinking and harms among girls . Reduction of problems among boys remains a challenge Objective . The purpose of this study was to compare the effects of a single drug , i.e. , alcohol , against a multiple drug preventive intervention . Methods . A controlled trial was conducted with 448 8th grade students ( mean age = 13 years old ) from an inner-city middle school ( n = 216 ) and a rural junior high school ( n = 232 ) in 2000–2001 . Students were r and omized within school , and 3-month post-intervention follow-up data were collected . Results . Two risk/protective factors were found to differ significantly in favor of youth receiving the single drug alcohol intervention ( p 's = 0.03 ) , while the frequency of alcohol use and two additional risk/protective factors approached significance ( p 's < 0.10 ) . Conclusion . These findings support the potential efficacy of a brief , single drug preventive intervention over a brief , multi-drug intervention in producing short-term alcohol outcomes for adolescents , and indicate differential effects of interventions for subgroups of substance using youth AIMS To establish the long-term efficacy of a universal internet-based alcohol and cannabis prevention programme in schools . METHODS A cluster-r and omized controlled trial was conducted to assess the effectiveness of the Climate Schools : Alcohol and Cannabis Course . The evidence -based course , aim ed at reducing alcohol and cannabis use , is facilitated by the internet and consists of 12 novel and curriculum consistent lessons delivered over 6 months . PARTICIPANTS A total of 764 year 8 students ( 13 years ) from 10 Australian secondary schools were allocated r and omly to the internet-based prevention programme ( n = 397 , five schools ) , or to their usual health classes ( n = 367 , five schools ) . MEASURES Participants were assessed at baseline , immediately post , and 6 and 12 months following completion of the intervention , on measures of alcohol and cannabis knowledge , attitudes , use and related harms . RESULTS This paper reports the final results of the intervention trial , 12 months following the completion of the Climate Schools : Alcohol and Cannabis Course . The effectiveness of the course 6 months following the intervention has been reported previously . At the 12-month follow-up , compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge , a reduction in average weekly alcohol consumption and a reduction in frequency of drinking to excess . No differences between groups were found on alcohol expectancies , cannabis attitudes or alcohol- and cannabis-related harms . The course was found to be acceptable by teachers and students as a means of delivering drug education in schools . CONCLUSIONS Internet-based prevention programs for school-age children can improve student 's knowledge about alcohol and cannabis , and may also reduce alcohol use twelve months after completion OBJECTIVE To establish the efficacy of an internet based prevention program to reduce alcohol and cannabis use in adolescents . METHOD A cluster r and omised controlled trial was conducted with 764 13-year olds from ten Australian secondary schools in 2007 - 2008 . Half the schools were r and omly allocated to the computerised prevention program ( n=397 ) , and half to their usual health classes ( n=367 ) . The Climate Schools : Alcohol and Cannabis prevention course is facilitated by the internet and consists of novel , evidence -based , curriculum consistent lessons aim ed at reducing alcohol and cannabis use . Participants were assessed at baseline , immediately post , and at six months following the intervention . RESULTS Compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge at the end of the course and the six month follow-up . In addition , the intervention group showed a reduction in average weekly alcohol consumption and frequency of cannabis use at the six month follow-up . No differences between groups were found on alcohol expectancies , cannabis attitudes , or alcohol and cannabis related harms . CONCLUSIONS The course is acceptable , scalable and fidelity is assured . It increased knowledge regarding alcohol and cannabis , and decreased use of these drugs |
2,120 | 24,085,592 | Despite this , there was some indication that the most effective interventions were those that offered both individual and group support for changing PA levels using a tailored approach .
Although we found evidence to support the effectiveness of face-to-face interventions for promoting PA , at least at 12 months , the effectiveness of these interventions was not supported by high quality studies .
Due to the clinical and statistical heterogeneity of the studies , only limited conclusions can be drawn about the effectiveness of individual components of the interventions . | BACKGROUND Face-to-face interventions for promoting physical activity ( PA ) are continuing to be popular but their ability to achieve long term changes are unknown .
OBJECTIVES To compare the effectiveness of face-to-face interventions for PA promotion in community dwelling adults ( aged 16 years and above ) with a control exposed to placebo or no or minimal intervention . | Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral BACKGROUND Using peer volunteers as delivery agents may improve translation of evidence -based physical activity promotion programs for older adults . This study examined whether tailored support from older peer volunteers could improve initiation and long-term maintenance of physical activity behavior . METHODS Participants were r and omized to 2 16-week , group-based programs : ( 1 ) peer-delivered , theory-based support for physical activity behavior change ; or ( 2 ) an intervention typically available in community setting s ( basic education , gym membership , and pedometer for self-monitoring ) , attention-matched with health education . Moderate-to-vigorous physical activity ( MVPA ) was assessed via daily self-report logs at baseline , at the end of the intervention ( 16 weeks ) , and at follow-up ( 18 months ) , with accelerometry validation ( RT3 ) in a r and om sub sample . RESULTS Seven peer volunteers and 81 sedentary adults were recruited . Retention at the end of the trial was 85 % and follow-up at 18 months was 61 % . Using intent-to-treat analyses , at 16 weeks , both groups had similar significant improvements in MVPA . At 18 months , the group supplemented with peer support had significantly more MVPA . CONCLUSIONS Trained peer volunteers may enhance long-term maintenance of physical activity gains from a community-based intervention . This approach has great potential to be adapted and delivered inexpensively in community setting Background Following an extensive recruitment campaign , a 16-week lunchtime intervention to increase walking was implemented with insufficiently physically active University employees to examine programme feasibility and the effects of the programme in increasing walking behaviour , and in improving well-being and work performance . Methods / design A feasibility study in which participants were r and omised to an immediate treatment or a delayed treatment control ( to start at 10 weeks ) group . For the first ten weeks of the intervention , participants took part in three facilitator-led group walks per week each of thirty minutes duration and were challenged to accumulate another sixty minutes of walking during the weekends . In the second phase of the intervention , the organised group walks ceased to be offered and participants were encouraged to self-organise their walks . Motivational principles were employed using contemporary motivational theory . Outcome measures ( including self-reported walking , step counts , cardiovascular fitness , general and work-related well-being and work performance ) were assessed at baseline , at the end of the 16-week intervention and ( for some ) four months after the end of the intervention . Process and outcome assessment s were also taken throughout , and following , the intervention . Discussion The results of the intervention will determine the feasibility of implementing a lunchtime walking programme to increase walking behaviour , well-being and performance in sedentary employees . If successful , there is scope to implement definitive trials across a range of worksites with the aim of improving both employee and organisational health . Trial registration Current Controlled Trials IS RCT N81504663 Mediation analyses in faith-based physical activity ( PA ) interventions targeting African-American adults are lacking . The purpose of this study was to examine the psychosocial mediators of a faith-based PA intervention with African-American adults . Churches were r and omly assigned to receive immediate or delayed ( 1-year later ) training in PA program implementation . A sub sample of participants from r and omly selected churches took part in telephone surveys at baseline and at 1 year . The primary outcome was percentage of participants meeting PA recommendations . MacKinnon 's product of coefficients was used to test for mediation . Participants ( n = 418 ) from 20 churches completed the baseline and 1-year follow-up surveys . There were no statistically significant changes in PA behavior at 1 year . The intervention had a marginally significant effect on increasing the amount of instrumental church support received by church members . However , none of the psychosocial variables tested were found to be significant mediators of the intervention . Mediation analyses provided insight into potential reasons as to why the Health-e-AME intervention did not change PA . The intervention did not successfully change the targeted mediators hypothesized to change PA . Potential reasons for these shortcomings as well as issues to address in future faith-based studies are discussed This paper reports on the cost-effectiveness of pedometer-based versus time-based Green Prescriptions in improving physical activity and health-related quality of life ( EQ-5D ) in a r and omised controlled trial of 330 low-active , community-based adults aged 65 years and over . Costs , measured in $ NZ ( NZ$1=A$0.83 , December 2008 ) , comprised public and private health care costs plus exercise-related personal expenditure . Based on intention-to-treat data at 12-month follow up , the pedometer group showed a greater increase in weekly leisure walking ( 50.6 versus 28.1min for the time-based group , adjusted means , P=0.03 ) . There were no significant between-group differences in costs . The incremental cost-effectiveness ratios , for the pedometer-based versus time-based Green Prescription , per 30min of weekly leisure walking and per quality -adjusted life year were , ( i ) when including only community care costs , $ 115 and $ 3105 , ( ii ) when including only exercise and community care costs , $ 130 and $ 3500 , and ( iii ) for all costs , -$185 and -$4999 , respectively . The cost-effectiveness acceptability curves showed that the pedometer-based compared with the time-based Green Prescription was statistically cost-effective , for the above cost categories , at the following quality -adjusted life year thresholds : ( i ) $ 30000 ; ( ii ) $ 30500 ; and ( iii ) $ 16500 . The additional program cost of converting one sedentary adult to an active state over a 12-month period was $ 667 . The outcomes suggest the pedometer-based Green Prescription may be cost-effective in increasing physical activity and health-related quality of life over 12 months in previously low-active older adults BACKGROUND Physical activity promotion is a priority , but contribution of physicians ' interventions is unclear . The effectiveness of the PEPAF ( " Experimental Program for Physical Activity Promotion " ) , which was implemented exclusively by physicians in routine primary care from October 2003 to December 2004 , was assessed . METHODS Fifty-six Spanish family physicians were r and omized to either the intervention ( n = 29 ) or st and ard care ( n = 27 ) arm of the trial . The physicians recruited 4317 physically inactive patients ( 2248 for intervention and 2069 for control protocol s ) from a systematic sample after assessing their physical activity in routine practice . Intervention physicians provided advice to all patients and a physical activity prescription to the subgroup attending an additional appointment ( 30 % ) . The main outcome measure was the change in physical activity measured by blinded nurses using the 7-Day Physical Activity Recall . Secondary outcomes included cardiorespiratory fitness and health-related quality of life . RESULTS At 6 months , intervention patients increased physical activity more than controls ( adjusted difference , 18 min/wk [ 95 % confidence interval , 6 - 31 min/wk ] ; metabolic equivalent tasks x hours per week , 1.3 [ 95 % CI , 0.4 - 2.2 ] ) . The proportion of the population achieving minimal physical activity recommendations was 3.9 % higher in the intervention group ( 1.2%-6.9 % ; number needed to treat , 26 ) . No differences were found in secondary outcomes . The effect of intervention was positively modified in subjects older than 50 years ( P < or = .01 ) and in the prescription subgroup ( P < .001 ) . CONCLUSIONS Family physicians were effective for increasing physical activity of primary care patients . Overall clinical effect was small but relevant for population public health . Within the intervention program , clinical ly relevant effects were seen in patients receiving a physical activity prescription . Trial Registration clinical trials.gov Identifier : NCT00131079 Background Limited data are available on the development , implementation and evaluation processes of physical activity promotion programmes among older adults . More integrative insights into interventions describing the planned systematic development , implementation and evaluation are needed . Methods and design The purpose of this study is to give an integrative insight into the development of the Active plus programme applying the six-step Intervention Mapping protocol . The Active plus programme consisted of two theory- and evidence -based tailored physical activity promotion interventions , both comprising three tailored letters delivered over four months and aim ed at raising awareness of insufficient physical activity , and stimulating physical activity initiation and maintenance among the over-fifties . The first intervention , the basic tailored intervention , provided tailored letters that intervened on the psychosocial determinants of physical activity . The second intervention , the intervention plus , provided the same tailored information but additionally provided tailored information about physical activity opportunities in the specific environment in which the older adults lived . This environment-based component also provided access to a forum and e-buddy system on a website . A plan for implementation and evaluation is also described . Discussion The planned development of the Active plus programme result ed in two theory- and evidence -based tailored physical activity interventions targeted at the over-fifties . Trial Registration Dutch Trial Register NTR OBJECTIVE We evaluate the 6-month efficacy of Keep Active Minnesota , a phone- and mail-based physical activity maintenance intervention design ed for use with adults age 50 to 70 years who have increased their physical activity within the past year . METHOD Participants ( N=1049 ) recruited in 2004 and 2005 from one large managed-care organization in Minnesota were r and omly assigned to either treatment ( N=523 ) or usual care ( N=526 ) with physical activity assessed using the Community Healthy Activities Model Program for Seniors question naire , and expressed as kcal/week expenditures . RESULTS Total physical activity at baseline was similar for treatment and usual care participants ( p<0.44 ) as was moderate/vigorous physical activity ( p<0.21 ) . Maintenance of physical activity was higher among treatment participants whose mean 6-month change in total kcal/week energy expenditure was -91 , compared to -683 for usual care participants ( p<0.002 ) . Mean 6-month change in kcal/week expenditure in moderate or vigorous activities was -49 for treatment participants , compared to -612 for usual care participants ( p<0.001 ) . CONCLUSIONS This phone- and mail-based physical activity maintenance intervention is efficacious at maintaining physical activity at 6 months Background Scotl and has a policy aim ed at increasing physical activity levels in the population , but evidence on how to achieve this is still developing . Studies that focus on encouraging real world participants to start physical activity in their setting s are needed . The Walking for Well-being in the West study was design ed to assess the effectiveness of a pedometer-based walking programme in combination with physical activity consultation . The study was multi-disciplinary and based in the community . Walking for Well-being in the West investigated whether Scottish men and women , who were not achieving the current physical activity recommendation , increased and maintained walking behaviour over a 12 month period . This paper outlines the rationale and design of this innovative and pragmatic study . Methods Participants were r and omised into two groups : Group 1 : Intervention ( pedometer-based walking programme combined with a series of physical activity consultations ) ; Group 2 : Waiting list control for 12 weeks ( followed by minimal pedometer-based intervention ) . Physical activity ( primary outcome ) was measured using pedometer step counts ( 7 day ) and the International Physical Activity Question naire ( long version ) . Psychological processes were measured using question naires relating to the Transtheoretical Model of Behaviour Change , mood ( Positive and Negative Affect Schedule ) and quality of life ( Euroqol EQ-5D instrument ) . Physiological measures included anthropometric and metabolic outcomes . Environmental influences were assessed subjectively ( Neighbourhood Quality of Life Survey ) and objective ly ( neighbourhood audit tool and GIS mapping ) . The qualitative evaluation employed observation , semi-structured interviews and focus groups . A supplementary study undertook an economic evaluation . Discussion Data analysis is on-going . Walking for Well-being in the West will demonstrate if a pedometer based walking programme , in combination with physical activity consultation results in a sustainable increase in walking behaviour in this sample of Scottish adults over a 12 month period . The study will examine the complex relationships between behavioural change , health consequences and the role of the environment , in conjunction with the cost effectiveness of this approach and a detailed insight into the participants ' experiences of the intervention . Trial registration Current Controlled Trials IS RCT Background Recent systematic review s have suggested that pedometers may be effective motivational tools to promote walking . However , studies tend to be of a relatively short duration , with small clinical based sample s. Further research is required to demonstrate their effectiveness in adequately powered , community based studies . Objective Using a r and omized controlled trial design , this study assessed the impact of a 12-week graduated pedometer-based walking intervention on daily step-counts , self-reported physical activity and health outcomes in a Scottish community sample not meeting current physical activity recommendations . MethodS ixty-three women and 16 men ( 49.2 years ± 8.8 ) were r and omly assigned to either an intervention ( physical activity consultation and 12-week pedometer-based walking program ) or control ( no action ) group . Measures for step-counts , 7-day physical activity recall , affect , quality of life ( n = 79 ) , body mass , BMI , % body fat , waist and hip circumference ( n = 76 ) , systolic/diastolic blood pressure , total cholesterol and HDL cholesterol ( n = 66 ) were taken at baseline and week 12 . Analyses were performed on an intention to treat basis using 2-way mixed factorial analyses of variance for parametric data and Mann Whitney and Wilcoxon tests for non-parametric data . Results Significant increases were found in the intervention group for step-counts ( p < .001 ) , time spent in leisure walking ( p = .02 ) and positive affect ( p = .027 ) . Significant decreases were found in this group for time spent in weekday ( p = .003 ) , weekend ( p = .001 ) and total sitting ( p = .001 ) with no corresponding changes in the control group . No significant changes in any other health outcomes were found in either group . In comparison with the control group at week 12 , the intervention group reported a significantly greater number of minutes spent in leisure time ( p = .008 ) , occupational ( p = .045 ) and total walking ( p = .03 ) , and significantly fewer minutes in time spent in weekend ( p = .003 ) and total sitting ( p = .022 ) . Conclusion A pedometer-based walking program , incorporating a physical activity consultation , is effective in promoting walking and improving positive affect over 12 weeks in community based individuals . The discussion examines possible explanations for the lack of significant changes in health outcomes . Continued follow-up of this study will examine adherence to the intervention and possible result ing effects on health outcomes Background Ageing is associated with a decrease in physical activity . This decrease particularly occurs during specific transitional life stages . Especially during adolescence and young adulthood a steep decrease in physical activity is observed . Inactive people are often not aware of their inactivity . Providing feedback on the actual physical activity level by an activity monitor can increase awareness and may in combination with an individually tailored physical activity advice stimulate a physically active lifestyle . Methods In a r and omized controlled trial the effectiveness of providing an activity monitor in combination with a personal physical activity advice through the Internet will be examined . Outcome measures are level of physical activity , determinants of physical activity , quality of life , empowerment , aerobic fitness and body composition . Participants are relatively inactive adolescents and young adults who are measured at baseline , after 3 months intervention and 5 months after the end of the intervention . In addition , facilitating and hindering factors for implementation of the intervention will be investigated . Discussion The use of a personal activity monitor in combination with web-based assisted individually tailored health promotion offers a good opportunity to work interactively with large groups of adolescents and young adults and provide them with advice based on their actual activity level . It has great potential to motivate people to change their behaviour and to our knowledge has not been evaluated before Background Grade d health benefits of physical activity have been demonstrated for the reduction of coronary heart disease , some cancers , and type-2 diabetes , and for injury reduction and improvements in mental health . Older adults are particularly at risk of physical inactivity , and would greatly benefit from successful targeted physical activity interventions . Methods / Design The Healthy Steps study is a 12-month r and omized controlled trial comparing the efficacy of a pedometer-based Green Prescription with the conventional time-based Green Prescription in increasing and maintaining physical activity levels in low-active adults over 65 years of age . The Green Prescription interventions involve a primary care physical activity prescription with 3 follow-up telephone counselling sessions delivered by trained physical activity counsellors over 3 months . Those in the pedometer group received a pedometer and counselling based around increasing steps that can be monitored on the pedometer , while those in the st and ard Green Prescription group received counselling using time-based goals . Baseline , 3 month ( end of intervention ) , and 12 month measures were assessed in face-to-face home visits with outcomes measures being physical activity ( Auckl and Heart Study Physical Activity Question naire ) , quality of life ( SF-36 and EQ-5D ) , depressive symptoms ( Geriatric Depression Scale ) , blood pressure , weight status , functional status ( gait speed , chair st and s , and t and em balance test ) and falls and adverse events ( self-report ) . Utilisation of health services was assessed for the economic evaluation carried out alongside this trial . As well , a process evaluation of the interventions and an examination of barriers and motives for physical activity in the sample were conducted . The perceptions of primary care physicians in relation to delivering physical activity counselling were also assessed . Discussion The findings from the Healthy Steps trial are due in late 2009 . If successful in improving physical activity in older adults , the pedometer-based Green Prescription could assist in reducing utilisation of health services and improve cardiovascular health and reduction of risk for a range of non-communicable lifestyles diseases . Trial registration Australian and New Zeal and Clinical Trials Registry INTRODUCTION Project Graduate Ready for Activity Daily evaluated a program to promote physical activity through the transition of university graduation in a r and omized controlled trial . METHODS Three hundred thirty-eight university seniors participated in either a cognitive-behavioral intervention course or a knowledge-oriented general health course during the semester before graduation . Behaviorally oriented phone and mail follow-up was delivered to the intervention group for 18 months . Physical activity outcomes and mediating variables were assessed at baseline , 1 and 2 years ( 93 % retention rate ) . RESULTS There were no significant intervention effects on physical activity outcomes at 2 years for either men or women . Experiential and behavioral processes of change were significantly improved for intervention women over 2 years . CONCLUSIONS Despite excellent participation in a theoretically based , well-attended intervention , few long-term effects on physical activity or its mediators were found . Additional research is needed to determine optimal interventions for physical activity and to vali date or alter current behavior change theory Background Pedometers provide a simple , cost effective means of motivating individuals to increase walking yet few studies have considered if short term changes in walking behaviour can be maintained in the long-term . The role of physical activity consultations in such interventions is unclear . The purpose of this study was to assess the sustainability of pedometer-based interventions and empirically examine the role of physical activity consultations using long-term results of a community-based walking study . Methods 79 low active Scottish men and women ( 63 women and 16 men ) from the Walking for Wellbeing in the West intervention study were r and omly assigned to receive either : Group 1 ; pedometer-based walking programme plus physical activity consultations or Group 2 ; pedometer-based walking programme and minimal advice . Step counts ( Omron HJ-109E Step-O-Meter pedometer ) , 7 day recall of physical activity ( IPAQ long ) , mood ( PANAS ) and quality of life ( EuroQol EQ-5D ) were assessed pre-intervention and 12 , 24 and 48 weeks after receiving the intervention . Body mass , body mass index and waist and hip circumference were assessed pre-intervention and 12 and 24 weeks after receiving the intervention . Analyses were performed on an intention to treat basis ( baseline value carried forward for missing data ) using mixed-factorial ANOVAs and follow-up t-tests . Results A significant main effect of time ( p < 0.001 ) was found for step-counts attributable to significant increases in steps/day between : pre-intervention ( M = 6941 , SD = 3047 ) and 12 weeks ( M = 9327 , SD = 4136 ) , t(78 ) = - 6.52 , p < 0.001 , d = 0.66 ; pre-intervention and 24 weeks ( M = 8804 , SD = 4145 ) , t(78 ) = - 4.82 , p < 0.001 , d = 0.52 ; and pre-intervention and 48 weeks ( M = 8450 , SD = 3855 ) , t(78 ) = - 4.15 , p < 0.001 , d = 0.44 . Significant effects were found for several variables of self-reported physical activity , mood and quality of life and are discussed . No other significant effects in health related outcomes were found . Conclusion Both interventions successfully increased and maintained step counts over 12 months . Physical activity consultations may encourage individuals to be active in other ways beyond walking and to reduce sitting time . Trial Registration NumberCurrent Controlled Trials Ltd IS RCT BACKGROUND Few primary care physicians routinely counsel for exercise , despite the benefits of physical activity and the high prevalence of inactivity . The objective of this study is to assess the effectiveness of Physician-Based Assessment and Counseling for Exercise ( PACE ) , a brief , behavior-based tool for primary care providers counseling healthy adults . METHODS This study is a r and omized controlled trial of 812 patients age 30 years or older registered for well visits at 32 primary care physician offices at a staff model health maintenance organization . Intervention physicians were trained to deliver PACE exercise counseling protocol s at the index visit , and one reminder telephone call occurred at 1 month . An enhanced intervention group received additional activity reminders . RESULTS At the 6-month follow-up , the control group did not differ significantly from the intervention group for energy expended ( 2,048 kcal/week versus 2,108 kcal/ week , P = 0.77 ) , time spent in walking or other moderate to vigorous activities ( 202 min/week versus 187 min/ week , P = 0.99 ) , mental health , physical function , or behaviors previously shown to predict activity change . Among the intervention patients , the stages-of-change score for Contemplators increased significantly compared with controls ( P = 0.03 ) , but without a significant change in energy expended . Baseline levels of physical activity counseling were high ( 50 % ) , as were baseline patient physical activity levels ( 61 % exercised at least three times a week ) . CONCLUSIONS These results suggest that a one-time PACE counseling session with minimal reinforcement , in a setting with high baseline levels of activity , does not further increase activity . The finding that Contemplators advanced in stage of behavior change suggests that further studies are needed to examine long-term , repeated counseling interventions During the postpartum period , ethnic minority women have higher rates of inactivity/under-activity than white women . The Nā Mikimiki ( “ the active ones ” ) Project is design ed to increase moderate-to-vigorous physical activity over 18 months among multiethnic women with infants 2–12 months old . The study was design ed to test , via a r and omized controlled trial , the effectiveness of a tailored telephone counseling of moderate-to-vigorous physical activity intervention compared to a print/website material s-only condition . Healthy , underactive women ( mean age = 32 ± 5.6 years ) with a baby ( mean age = 5.7 ± 2.8 months ) were enrolled from 2008–2009 ( N = 278 ) . Of the total sample , 84 % were ethnic minority women , predominantly Asian – American and Native Hawaiian . Mean self-reported baseline level of moderate-to-vigorous physical activity was 40 minutes/week with no significant differences by study condition , ethnicity , infant 's age , maternal body mass index , or maternal employment . Women had high scores on perceived benefits , self-efficacy , and environmental support for exercise but low scores on social support for exercise . This multiethnic sample 's demographic and psychosocial characteristics and their perceived barriers to exercise were comparable to previous physical activity studies conducted largely with white postpartum women . The Nā Mikimiki Project 's innovative tailored technology-based intervention and unique population are significant contributions to the literature on moderate-to-vigorous physical activity in postpartum women Purpose . This study examined the broader use of a print-media intervention , which was previously shown to be effective at promoting physical activity to participants recruited from a regional Australian community , as a strategy suitable for a more diverse statewide population sample . Methods . Participants were r and omly selected adults who responded to a telephone interview conducted by the New South Wales Health Department and consented to participate in a r and omized controlled trial . Consenters were allocated to either intervention ( n = 361 ) or control ( n = 358 ) conditions . The intervention , a personalized letter plus stage-targeted booklets , was sent 1 week postbaseline . Data were collected via telephone interview at baseline and 2 and 8 months and were analyzed using repeated measures analysis of variance ( ANOVA ) and χ2 statistics . Results . The groups were similar at baseline ( mean age 43 ± 3 years ; 64 % women ) . Process evaluation showed high intervention recall ( 76 % at 2 months ) and high follow-up response rates ( > 85 % at 8 months ) were achieved . Nonsignificant increases in physical activity were observed ( F 1,719 = 2.18 , p = .14 ) . Discussion . A single mailing of stage-targeted print material s was not effective in promoting increases in physical activity among participants selected from the statewide population . Future research could examine how the effectiveness of print media might be enhanced , possibly by using supplementary media , community-based prompts , or other incentives Purpose . To examine the efficacy of a stage-targeted physical activity intervention among low-income African-Americans . Methods . 207 participants were r and omly assigned to groups and administered baseline measures . Intervention participants were mailed stage-targeted physical activity information , whereas control participants received low-sodium diet brochures . Measures were readministered by phone 1 and 6 months later , with response rates of 69 % and 46 % , respectively . Results . 69 % of participants were African-American and 64 % had a monthly household income of < $ 1000 . A doubly-multivariate analysis of variance indicated that intervention participants reported more physical activity than control participants at 1 month ( F(1 , 204 ) = 4.03 , p < .05 ) . Unlike control participants , intervention participants reported significant stage progression at 1 month , according to a McNemar χ2 test . Gains attenuated by 6 months . Conclusions . The current study supports the use of this intervention among low-income African-Americans . Limitations include use of self-report measures and small sample size Background Attempts to demonstrate the efficacy of interventions aim ed at increasing physical activity ( PA ) have been mixed . Further , studies are seldom design ed in a manner that facilitates the underst and ing of how or why a treatment is effective or ineffective and PA intervention design s should be guided by a heavier reliance upon behavioral theory . The use of a mediating variable framework offers a systematic method ological approach to testing the role of theory , and could also identify the effectiveness of specific intervention components . The primary purpose of this paper was to test the mediating role that cognitive constructs may have played in regards to the positive effect that a workplace behavioral intervention had on leisure-time PA for women . A subsidiary purpose was to examine the cross-sectional relationships of these cognitive constructs with PA behavior . Methods The Physical Activity Workplace Study was a r and omized controlled trial which compared the effects of stage-matched and st and ard print material s upon self-reported leisure-time PA , within a workplace sample at 6 and 12-months . In this secondary analysis we examined the mediation effects of 14 psychosocial constructs across 3 major social-cognitive theories which were operationalized for the intervention material s and measured at baseline , 6 and 12-months . We examined change in PA and change in the psychological constructs employing a mediation strategy proposed by Baron and Kenny for : ( 1 ) the first 6-months ( i.e. , initial change ) , ( 2 ) the second 6-months ( i.e. , delayed change ) , and ( 3 ) the entire 12-months ( overall change ) of the study on 323 women ( n = 213 control/st and ard material s group ; n = 110 stage-matched material s group ) . Results Of the 14 constructs and 42 tests ( including initial , delayed and overall change ) two positive results were identified ( i.e. , overall change in pros , initial change in experiential powerful intervention approaches processes ) , with very small effect sizes . However , these mediating results were eliminated after adjusting for the multiple statistical tests . Conclusions The intervention did not change these mediators in any substantive way , and show a similar pattern to prior research where interventions generally do not result in a change in mediation of behavior change . It is important to report mediation results in r and omized controlled trials whether the findings are null or positive . Future studies may wish to focus on more detailed dose-response issues between mediators and behavior , the inclusion of moderators that could affect individual change , or different mediator constructs at higher levels of measurement specificity . Continued work on innovative and more powerful PA intervention approaches are needed The Flexibility , Toning , and Balance ( FlexToBa ) Trial is a two-armed r and omized controlled trial which will contrast the effects of a DVD-delivered , home-based , physical activity intervention and a Healthy Aging attention control condition on physical activity , functional performance , functional limitations , and quality of life in low active , older adults . This innovative trial will recruit 300 participants across central Illinois who will be r and omized into the intervention arm or control arm of the study . The intervention will last 6 months with a 6 month follow-up . Assessment s at baseline , post intervention and follow-up will include physical activity ( self-report and accelerometry ) , a battery of functional performance measures , functional limitations , quality of life , and an array of psychological health measures . In addition , measures of external validity will be included to determine public health significance of a successful outcome . Participants will engage in a progressive series of activities focusing on flexibility , strengthening , and balance exercises which are demonstrated by a trained exercise leader and age-appropriate models on a series of DVDs . Delivery of the intervention has its basis in social cognitive theory . The specific aims of the trial are ( a ) to determine the effects of the DVD-delivered FlexToBa program on physical activity , functional performance , functional limitations , and quality of life , ( b ) to examine the mediators of the relationships between physical activity and functional limitations and quality of life , ( c ) to assess external validity indicators relative to the intervention , and ( d ) to determine differential effects of the intervention on psychosocial health measures Increasing physical activity is currently considered to be a possible prevention strategy for cancer , obesity , and cardiovascular disease , either alone or in combination with dietary changes . This paper presents results of a r and omized trial of moderate-to-vigorous intensity exercise in middle aged , sedentary women ; specifically , we report changes in and correlates of quality of life and functional status of this exercise intervention program for both the short ( three months ) and longer term ( 12 months ) . The intervention group showed a significant increase in Mental Health score from baseline to 3 months ( p < .01 ) , significantly greater than the change in the control group at 3 months ( p < .01 ) . A similar trend among exercisers was observed for the General Health score ( p < .01 ) , and this finding was significantly greater than the change in control group at 3 months ( p = .01 ) . Change in Social Support – Affection were predictors of the changes in quality of life variables . This study documented improvements in quality of life and general functioning that occurred as a result of participating in an exercise intervention in sedentary middle-aged women Background : Promoting physical activity is an important public health strategy for long-term reductions in incidence or severity of clinical disease . Benefits to health-related quality of life ( HRQL ) and subjective well-being may be as important and take less time to accrue . Purpose : We examined the HRQL benefits of a social-cognitive-theory-based intervention of the Activity Counseling Trial ( ACT ) , both directly in terms of changes in physical fitness and indirectly from increased self-efficacy associated with the intervention . Methods : In ACT , 395 female and 479 male inactive patients ages 35 to 75 years were r and omized to one of : physician advice , advice plus behavioral counseling during primary care visits , or advice plus behavioral counseling that also included telephone contact and behavioral classes . Participants were assessed at baseline , 6 months , and 24 months . HRQL was assessed as perceived quality of life , perceived stress , depression , and general health . Satisfaction with function and appearance , self-efficacy , and social support were also assessed . Results : At 24 months women who received counseling or assistance had significant reductions in daily stress and improvements in satisfaction with body function compared to those receiving advice only . Men had reductions in daily stress across all treatment arms . These results mirrored V02max changes observed per group . Change in barriers self-efficacy was significantly associated with reductions in daily stress at 24 months . Conclusions : Patient benefit from ACT intervention was mediated by enhanced cardiorespiratory fitness and by barriers self-efficacy Background Important health benefits can be derived when low-cost ( e.g. , computer-tailored ) physical activity interventions for older adults demonstrate sustained effects . Purpose The purpose of the study was to conduct in-depth analysis on the long-term efficacy of two tailored physical activity interventions for older adults . Methods A r and omized controlled trial ( n = 1,971 ) with two computer-tailored interventions and a no-intervention control group was conducted . The two tailored interventions consisted of three tailored letters , delivered during 4 months . The basic tailored intervention targeted psychosocial determinants alone , while the environmentally tailored intervention additionally targeted environmental determinants , by providing tailored environmental information . Self-reported behaviors ( i.e. , total physical activity , transport walking and cycling , leisure walking and cycling , and sports ) were measured at baseline and 12 months . Additionally , potential personal , health-related , and psychosocial moderators of the intervention effects were examined . Results The environmentally tailored intervention was effective in changing total physical activity , leisure cycling , and sports compared with the basic intervention and control group . No intervention effects were found for the basic intervention . Moderation analysis revealed that participants with a higher age , lower body mass index , and higher intention were unresponsive to the interventions . Conclusions Providing environmental information is an effective intervention strategy for increasing physical activity behaviors among older adults , especially among certain “ at-risk ” subgroups such as lower educated , overweight , or insufficiently active participants . Moderation analysis was perceived as a promising method for identifying meaningful subgroups that are unaffected by an intervention , which should receive special attention in future interventions Sedentary behavior among older adults increases risk for chronic diseases . Physicians in a primary care setting can play an important role in promoting physical activity adoption among their older patients . The Physically Active for Life ( PAL ) project was a r and omized , controlled trial comparing the efficacy of brief physician-delivered physical activity counseling to usual care on self-reported physical activity levels . The physical activity counseling was based on the Transtheoretical Model of Change and social learning theory . Twenty-four community-based primary care medical practice s were recruited into the study ; 12 were r and omized to the Intervention condition and 12 to the Control condition . Physicians in the Intervention practice s received training in the delivery of brief physical activity counseling . Subjects in the Intervention practice s ( n=181 ) received brief activity counseling matched to their stage of motivational readiness for physical activity , a patient manual , a follow-up appointment with their physician to discuss activity counseling , and newsletter mailings . Subjects in the Control practice s ( n=174 ) received st and ard care . Measures of motivational readiness for physical activity and the Physical Activity Scale for the Elderly ( PASE ) were administered to subjects in both conditions at baseline , 6 weeks following their initial appointment , and at 8 months . Results showed that at the 6-week follow-up , subjects in the Intervention condition were more likely to be in more advanced stages of motivational readiness for physical activity than subjects in the Control condition . This effect was not maintained at the 8 month follow-up and the intervention did not produce significant changes in PASE scores . Results suggest that more intensive , sustained interventions may be necessary to promote the adoption of physical activity among sedentary , middle-aged , and older adults in primary care medical practice Background : Ethnic minorities or those with low socioeconomic status ( SES ) are at increased risk of cardiovascular disease , type 2 diabetes , and all-cause mortality , compared to higher SES Whites . National surveys also indicate that low-income , ethnic minority women have the highest rates of inactivity in the United States . Purpose : This study ( the Increasing Motivation for Physical ACTivity or IMPACT study ) promoted adoption and maintenance of physical activity ( PA ) in sedentary , low-income women participating in federally funded job training programs . Methods : The study consisted of 2 months of weekly 1-hr classes , then r and om assignment to 10 months of either home-based telephone counseling for PA plus information and feedback via mailed newsletters ( Phone + Mail Counseling condition ) or just the mailed newsletters ( Mail Support condition ) . The IMPACT intervention included behavior change strategies for PA as well as discussion s related to motivational readiness for PA change . Participants completed surveys and physiological assessment s at baseline after the classes ended ( i.e. , at 10 weeks ) and at 6 and 12 months postbaseline . Seventy-three percent of r and omized participants ( n = 72 ) were Latina , with a mean age of 32 ± 10 years . More than half the women had not completed high school , and 73 % had an annual income less than $ 20,000 . Results : After 10 months of a homebased intervention , women in the phone + mail counseling condition had significantly greater increases in estimated total energy expenditure compared to women in the mail support condition ( p < .05 ) . Conclusions : Regular PA counseling delivered via the telephone and through the mail appears effective for encouraging regular PA among low-income women transitioning from welfare or job training to the workforce Background : Intervention trials with self-selected participants have shown that mailed stage-targeted print material s can increase participation in physical activity in the short term . We examined the effects of a mailed stage-targeted print intervention design ed to promote physical activity , in a r and om sample of adults living in a regional city . Method : Participants ( n = 462 , 40–60 years of age ) were r and omly allocated to an intervention in - 227 ) or control group ( n - 235 ) . Measures included vali date d 2-week physical activity recall and stage of motivational readiness for physical activity . The intervention consisted of a single mailing of a letter and full-color stage-targeted booklets ( specific to precontemplation , contemplation , preparation , and action/maintenance ) 1 week postbaseline . Follow-up interviews were conducted at 2 and 6 months postbaseline . Results : After 2 months , participants in the intervention group were significantly More likely to meet the current American College of Sports Medicine/Centers for Disease Control and Prevention recommendation for sufficient physical activity than those in the control group ( adjusted odds ratio [ OR ] - 2.40 ; 95 % confidence interval [ CI ] = 1.44–3.99 ) . After 6 months , intervention participants who reported receiving and reading the intervention material s were significantly more likely to be meeting the sufficient physical activity criterion compared with the control group ( adjusted OR = 2.03 ; 95 % Cl = 1.16–3.56 ) . Conclusions : The stage-targeted print intervention was effective in promoting short-term increases in physical activity and was most effective for participants who recognized and used the material s. This low-cost , generalizable intervention has demonstrated potential as a practical population -based physical activity promotion strategy . Further research is required before widespread dissemination would be justified , as additional strategies may be required to ensure sustained change Background Effective interventions are needed to reduce the chronic disease epidemic . The Internet has the potential to provide large population s with individual advice at relatively low cost . Objective The focus of the study was the Web-based tailored physical activity intervention Active-online . The main research questions were ( 1 ) How effective is Active-online , compared to a nontailored website , in increasing self-reported and objective ly measured physical activity levels in the general population when delivered in a real-life setting ? ( 2 ) Do respondents recruited for the r and omized study differ from spontaneous users of Active-online , and how does effectiveness differ between these groups ? ( 3 ) What is the impact of frequency and duration of use of Active-online on changes in physical activity behavior ? Methods Volunteers recruited via different media channels completed a Web-based baseline survey and were r and omized to Active-online ( intervention group ) or a nontailored website ( control group ) . In addition , spontaneous users were recruited directly from the Active-online website . In a subgroup of participants , physical activity was measured objective ly using accelerometers . Follow-up assessment s took place 6 weeks ( FU1 ) , 6 months ( FU2 ) , and 13 months ( FU3 ) after baseline . Results A total of 1531 respondents completed the baseline question naire ( intervention group n = 681 , control group n = 688 , spontaneous users n = 162 ) ; 133 individuals had valid accelerometer data at baseline . Mean age of the total sample was 43.7 years , and 1146 ( 74.9 % ) were women . Mixed linear models ( adjusted for sex , age , BMI category , and stage of change ) showed a significant increase in self-reported mean minutes spent in moderate- and vigorous-intensity activity from baseline to FU1 ( coefficient = 0.14 , P = .001 ) and to FU3 ( coefficient = 0.19 , P < .001 ) in all participants with no significant differences between groups . A significant increase in the proportion of individuals meeting the HEPA recommendations ( self-reported ) was observed in all participants between baseline and FU3 ( OR = 1.47 , P = .03 ) , with a higher increase in spontaneous users compared to the r and omized groups ( interaction between FU3 and spontaneous users , OR = 2.95 , P = .02 ) . There were no increases in physical activity over time in any group for objective ly measured physical activity . A significant relation was found between time spent on the tailored intervention and changes in self-reported physical activity between baseline and FU3 ( coefficient = 1.13 , P = .03 , intervention group and spontaneous users combined ) . However , this association was no longer significant when adjusting for stage of change . Conclusions In a real-life setting , Active-online was not more effective than a nontailored website in increasing physical activity levels in volunteers from the general population . Further research may investigate ways of integrating Web-based physical activity interventions in a wider context , for example , primary care or workplace health promotion Background The aim of this study was to explore the working mechanisms of a computer tailored physical activity intervention for older adults with environmental information compared to a basic tailored intervention without environmental information . Method A clustered r and omized controlled trial with two computer tailored interventions and a no-intervention control group was conducted among 1971 adults aged ≥ 50 . The two tailored interventions were developed using Intervention Mapping and consisted of three tailored letters delivered over a four-month period . The basic tailored intervention targeted psychosocial determinants alone , while the environmentally tailored intervention additionally targeted environmental determinants , by providing tailored environmental information . Study outcomes were collected with question naires at baseline , three and six months and comprised total physical activity ( days/week ) , walking ( min/week ) , cycling ( min/week ) , sports ( min/week ) , environmental perceptions and use and appreciation of the interventions . Results Mediation analyses showed that changes in cycling , sports and total physical activity behaviour induced by the environmentally tailored intervention were mediated by changes in environmental perceptions . Changes in environmental perceptions did not mediate the effect of the basic tailored intervention on behaviour . Compared with the basic tailored intervention , the environmentally tailored intervention significantly improved cycling behaviour ( τ = 30.2 ) . Additionally , the tailored letters of the environmentally tailored intervention were better appreciated and used , although these differences did not mediate the intervention effect . Discussion This study gave some first indications of the relevance of environmental perceptions as a determinant of changing physical activity behaviours and the potential effectiveness of providing environmental information as an intervention strategy aim ed at enhancing physical activity behaviour among older adults Background It is well recognised that the adoption and longer term adherence to physical activity by adults to reduce the risk of chronic disease is a challenge . Interventions , such as group and home based physical activity programs , have been widely reported upon . However few studies have directly compared these interventions over the longer term to determine their adherence and effectiveness . Participant preference for home based or group interventions is important . Some evidence suggests that home based physical activity programs are preferred by middle aged adults and provide better long term physical activity adherence . Physiotherapists may also be useful in increasing physical activity adherence , with limited research on their impact . Methods ' Physical Activity at Home ' is a 2 year pragmatic r and omised control trial , with a non-r and omised comparison to group exercise . Middle-aged adults not interested in , or unable to attend , a group exercise program will be targeted . Sedentary community dwelling 50 - 65 year olds with no serious medical conditions or functional impairments will be recruited via two mail outs using the Australian federal electoral roll . The first mail out will invite participants to a 6 month community group exercise program . The second mail out will be sent to those not interested in the group exercise program inviting them to take part in a home based intervention . Eligible home based participants will be r and omised into a 6 month physiotherapy-led home based physical activity program or usual care . Outcome measures will be taken at baseline , 6 , 12 , 18 and 24 months . The primary outcome is physical activity adherence via exercise diaries . Secondary outcomes include the Active Australia Survey , accelerometry , aerobic capacity ( step test ) , quality of life ( SF-12v2 ) , blood pressure , waist circumference , waist-to-hip ratio and body mass index . Costs will be recorded prospect ively and qualitative data will be collected . Discussion The planned 18 month follow-up post intervention will provide an indication of the effectiveness of the group and home based interventions in terms of adherence to physical activity , health benefits and cost . If the physiotherapy-led home based physical activity program is successful it could provide an alternative option for physical activity program delivery across a number of setting s . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : Two studies were undertaken to compare strategies for the adoption and maintenance of moderate-intensity , home-based exercise training . In the study of adoption , 52 men and women who had served for 6 months as controls for a study of moderate-intensity , home-based exercise training received 30 minutes of baseline instruction . They were then r and omized to receive continuing instruction and support through 10 staff-initiated telephone contacts of 5 minutes each every 2 weeks , or to receive no telephone contacts . In subjects receiving telephone contacts , peak oxygen uptake increased significantly after 6 months , whereas no increase was observed in subjects receiving no staff support ( p less than 0.05 ) . In the maintenance study , 51 men and women who had significantly increased their peak oxygen uptake by 6 months of moderate-intensity , home-based exercise training were r and omized to undergo daily self-monitoring and receive adherence instructions , or undergo weekly self-monitoring only , during a second 6-month period of training . Subjects performing daily self-monitoring reported completing significantly more exercise training sessions during the 6 months of training than subjects performing weekly self-monitoring ; functional capacity in both groups remained higher than before training ( p less than 0.05 ) . Taken together , these studies suggest that brief baseline instruction followed by continuing telephone contact with staff can be used to help people adopt a moderate-intensity , home-based exercise training program that can be maintained by simple self-monitoring strategies Background Increased physical activity levels benefit both an individuals ' health and productivity at work . The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention design ed to increase physical activity levels . Methods A total of 1260 participants from 44 UK worksites ( based within 5 organizations ) were recruited to a cluster r and omized controlled trial with worksites r and omly allocated to an intervention or control condition . Measurement of physical activity and other variables occurred at baseline , and at 0 months , 3 months and 9 months post-intervention . Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention . The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior , delivered in-house by nominated facilitators . Self-reported physical activity ( measured using the IPAQ short-form ) and health outcomes were assessed . Results and discussion Multilevel modelling found no significant effect of the intervention on MET minutes of activity ( from the IPAQ ) at any of the follow-up time points controlling for baseline activity . However , the intervention did significantly reduce systolic blood pressure ( B = -1.79 mm/Hg ) and resting heart rate ( B = -2.08 beats ) and significantly increased body mass index ( B = .18 units ) compared to control . The intervention was found not to be cost-effective , however the substantial variability round this estimate suggested that further research is warranted . Conclusions The current study found mixed support for this worksite physical activity intervention . The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale r and omized controlled trials in real-world setting s . Trial registration Current controlled trials IS RCT CONTEXT Physical activity is important for health , yet few studies have examined the effectiveness of physical activity patient counseling in primary care . OBJECTIVE To compare the effects of 2 physical activity counseling interventions with current recommended care and with each other in a primary care setting . DESIGN The Activity Counseling Trial , a r and omized controlled trial with recruitment in 1995 - 1997 , with 24 months of follow-up . SETTING Eleven primary care facilities affiliated with 3 US clinical research centers . PARTICIPANTS Volunteer sample of 395 female and 479 male inactive primary care patients aged 35 to 75 years without clinical cardiovascular disease . INTERVENTIONS Participants were r and omly assigned to 1 of 3 groups : advice ( n = 292 ) , which included physician advice and written educational material s ( recommended care ) ; assistance ( n = 293 ) , which included all the components received by the advice group plus interactive mail and behavioral counseling at physician visits ; or counseling ( n = 289 ) , which included the assistance and advice group components plus regular telephone counseling and behavioral classes . MAIN OUTCOME MEASURES Cardiorespiratory fitness , measured by maximal oxygen uptake ( VO(2)max ) , and self-reported total physical activity , measured by a 7-day Physical Activity Recall , compared among the 3 groups and analyzed separately for men and women at 24 months . RESULTS At 24 months , 91.4 % of the sample had completed physical activity and 77.6 % had completed cardiorespiratory fitness measurements . For women at 24 months , VO(2)max was significantly higher in the assistance group than in the advice group ( mean difference , 80.7 mL/min ; 99.2 % confidence interval [ CI ] , 8.1 - 153.2 mL/min ) and in the counseling group than in the advice group ( mean difference , 73.9 mL/min ; 99.2 % CI , 0.9 - 147.0 mL/min ) , with no difference between the counseling and assistance groups and no significant differences in reported total physical activity . For men , there were no significant between-group differences in cardiorespiratory fitness or total physical activity . CONCLUSIONS Two patient counseling interventions differing in type and number of contacts were equally effective in women in improving cardiorespiratory fitness over 2 years compared with recommended care . In men , neither of the 2 counseling interventions was more effective than recommended care OBJECTIVE To evaluate the cost-effectiveness of non-face-to-face interventions for increasing physical activity in sedentary adults . The study took place in Providence , Rhode Isl and between the years 2000 and 2004 . METHODS Two hundred and thirty-nine participants were r and omized to Phone , Print or a contact control . Phone and Print groups were mailed regular surveys regarding their level of physical activity , motivational readiness and self-efficacy . Surveys were scanned by a computer expert system to generate feedback reports . Phone group participants received feedback by telephone . Print group participants received feedback by mail . The contact control group received mailings unrelated to physical activity . Intervention costs were assessed prospect ively , from a payer perspective . Physical activity was measured using the 7-day Physical Activity Recall . Ambulatory health service use was assessed via monthly surveys . RESULTS The Print intervention was more economically efficient than the Phone intervention in engaging participants in a more active lifestyle . CONCLUSION The Print intervention provides an efficient approach to increasing physical activity . Research is needed to determine the cost-effectiveness of the intervention in a more diverse population , within the context of the health service delivery system and over a longer period of time Background Systematic review s have identified a range of brief interventions which increase physical activity in previously sedentary people . There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity . This study assesses whether it is worth providing motivational interviews , three months after giving initial advice , to those who have become more active . Methods / Design Study c and i date s ( n = 1500 ) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD . Only those that have increased their physical activity after three months ( n = 600 ) will be r and omised into the study . These participants will receive either a " mini booster " ( n = 200 ) , " full booster " ( n = 200 ) or no booster ( n = 200 ) . The " mini booster " consists of two telephone calls one month apart to discuss physical activity and maintenance strategies . The " full booster " consists of a face-to-face meeting with the facilitator at the same intervals . The purpose of these booster sessions is to help the individual maintain their increase in physical activity . Differences in physical activity , quality of life and costs associated with the booster interventions , will be measured three and nine months from r and omisation . The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield , which have large , ethnically diverse population s , high levels of economic deprivation , low levels of physical activity , poorer health and shorter life expectancy . Participants will be recruited through general practice s and community groups , as well as by postal invitation , to ensure the participation of minority ethnic groups and those with lower levels of literacy . Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities . A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10 % sample . Discussion The choice of study population , study interventions , brief intervention preceding the study , and outcome measure are discussed . Trial Registration Current Controlled Trials : IS RCT N56495859 ; Clinical Trials.gov : NCT00836459 BACKGROUND Sedentary lifestyle is associated with adverse health outcomes . Available evidence suggests that , despite positive attitudes toward regular exercise in promoting a healthy lifestyle , few physicians actually prescribe exercise for their patients . Barriers include lack of skills and st and ard office instruments . Because primary care physicians have regular contact with a large proportion of the population , the impact of preventive health interventions may be great . OBJECTIVES To determine the effect of an exercise prescription instrument ( i.e. , Step Test Exercise Prescription [ STEP ] ) , compared to usual-care exercise counseling delivered by primary care doctors on fitness and exercise self-efficacy among elderly community-dwelling patients . DESIGN R and omized controlled trial ; baseline assessment and intervention delivery with postintervention follow-up at 3 , 6 , and 12 months . SETTING Four large ( > 5000 active patient files ) academic , primary care practice s : three in urban setting s and one in a rural setting , each with four primary care physicians ; two clinics provided the STEP intervention and two provided usual care control . PARTICIPANTS A total of 284 healthy community-dwelling patients ( 72 per clinic ) aged > 65 years were recruited in 1998 - 1999 . INTERVENTION STEP included exercise counseling and prescription of an exercise training heart rate . MAIN OUTCOME MEASURES The primary outcome measure was aerobic fitness ( VO(2max ) ) . Secondary outcomes included predicted VO(2max ) from the STEP test , exercise self-efficacy ( ESE ) , and clinical anthropometric parameters . RESULTS A total of 241 subjects ( 131 intervention , 110 control ) completed the trial . VO(2max ) was significantly increased in the STEP intervention group ( 11 % ; 21.3 to 24ml/kg/min ) compared to the control group ( 4 % ; 22 to 23ml/kg/min ) over 6 months ( p < 0.001 ) , and 14 % ( 21.3 to 24.9ml/kg/min ) and 3 % ( 22.1 to 22.8ml/kg/min ) , respectively , at 12 months ( p < 0.001 ) . A similar significant increase in ESE ( 32 % ; 4.6 vs 6.8 ) was observed for the STEP group compared to the control group ( 22 % ; 4.2 vs 5.4 ) at 12 months ( p < 0.001 ) . Systolic blood pressure decreased 7.3 % and body mass index decreased 7.4 % in the STEP group , with no significant change in the control group ( p < 0.05 ) . Exercise counseling time was significantly ( p < 0.02 ) longer in the STEP ( 11.7+/-3.0 min ) compared to the control group ( 7.1+/-7.0 min ) , but more ( p < 0.05 ) subjects completed > or = 80 % of available exercise opportunities in the STEP group . CONCLUSIONS Primary care physicians can improve fitness and exercise confidence of their elderly patients using a tailored exercise prescription ( e.g. , STEP ) . Further , STEP appears to maintain benefits to 12 months and may improve exercise adherence . Future study should determine the impact of combining cognitive/behavior change strategies with STEP Background While there are increasing data implicating poor recognition of physical inactivity as a potential barrier to healthy behaviour change , the efficacy of feedback to promote physical activity is uncertain . Using a r and omised controlled trial nested within a population -based cohort study , we plan to test three variations of physical activity feedback against a control group . Our primary objective is to assess the efficacy of physical activity feedback in promoting physical activity behaviour change . Secondary objectives are to determine the influence of feedback on physical activity awareness and cognitions , and to compare behavioural effects by type of feedback . Methods / Design We aim to recruit 500 healthy participants aged 30 to 55 years from the ongoing Fenl and Study ( Cambridge , UK ) . Following careful phenotyping during baseline measurement ( anthropometric , clinical , body composition and fitness measurements , as well as question naires assessing self-reported and self-rated physical activity , psychosocial correlates of physical activity behaviour , diet , lifestyle and general health ) , participants wear a combined heart rate and movement sensor ( Actiheart ® ) for six continuous days and nights . After receipt of the physical activity data ( around 2 weeks later ) , participants are r and omly allocated to either a control group ( no feedback ) or one of three types of personalised physical activity feedback ( ' simple ' , ' visualised ' or ' context ualised ' ) , and complete repeat measures of self-rated physical activity and psychosocial correlates . Approximately five weeks after receiving feedback , all participants wear the Actiheart ® for another six-day follow-up period and complete repeat question naires . Values at outcome , adjusted for baseline , will be compared between r and omised groups . Discussion Given the r and omised trial design and use of objective measure of physical activity , this study is likely to provide valuable insights into the efficacy of a feedback intervention in changing physical activity behaviour , as well as the psychological mechanisms involved . Trial Registration Current Controlled Trials : IS RCT Background Epidemiological evidence suggests that decrease in sedentary behaviour is beneficial for health . This family based r and omized controlled trial examines whether face-to-face delivered counselling is effective in reducing sedentary time and improving health in adults and increasing moderate-to-vigorous activities in children . Methods The families are r and omized after balancing socioeconomic and environmental factors in the Jyväskylä region , Finl and . Inclusion criteria are : healthy men and women with children 3 - 8 years old , and having an occupation where they self-reportedly sit more than 50 % of their work time and children in all-day day-care in kindergarten or in the first grade in primary school . Exclusion criteria are : body mass index > 35 kg/m2 , self-reported chronic , long-term diseases , families with pregnant mother at baseline and children with disorders delaying motor development . From both adults and children accelerometer data is collected five times a year in one week periods . In addition , fasting blood sample s for whole blood count and serum metabonomics , and diurnal heart rate variability for 3 days are assessed at baseline , 3 , 6 , 9 , and 12 months follow-up from adults . Quadriceps and hamstring muscle activities providing detailed information on muscle inactivity will be used to realize the maximum potential effect of the intervention . Fundamental motor skills from children and body composition from adults will be measured at baseline , and at 6 and 12 months follow-up . Question naires of family-influence-model , health and physical activity , and dietary records are assessed . After the baseline measurements the intervention group will receive tailored counselling targeted to decrease sitting time by focusing on commute and work time . The counselling regarding leisure time is especially targeted to encourage toward family physical activities such as visiting playgrounds and non-built environments , where children can get diversified stimulation for play and practice fundamental of motor skills . The counselling will be reinforced during the first 6 months followed by a 6-month maintenance period . Discussion If shown to be effective , this unique family based intervention to improve lifestyle behaviours in both adults and children can provide translational model for community use . This study can also provide knowledge whether the lifestyle changes are transformed into relevant biomarkers and self-reported health . Trial registration numberIS RCT N : IS RCT OBJECTIVE To examine putative mediators of a 12-month motivationally tailored physical activity ( PA ) promotion intervention . DESIGN We r and omly assigned 239 healthy , underactive adults ( moderate-vigorous physical activity < 90 min/week ; mean age = 47.5 years ; 82 % women ) to receive ( a ) print-based feedback , ( b ) phone-based feedback , or ( c ) contact control . PRIMARY OUTCOME PA at baseline , 6 , and 12 months , as measured by the 7-day physical activity recall interview . MEDIATORS : Four TransTheoretical Model constructs explicitly targeted by the intervention ( i.e. , self-efficacy , decisional balance , cognitive and behavioral processes of change ) , as well as four additional constructs linked to PA behavior change ( i.e. , social support , outcome expectancy , PA enjoyment , exercise-induced feelings ) . RESULTS Multivariate mediation analyses were used to analyze longitudinal PA outcomes . Changes in behavioral processes and one aspect of exercise-induced feelings ( revitalization ) satisfied both action theory ( i.e. , treatment effects on mediators ) and conceptual theory ( i.e. , mediator effects on PA ) tests at 6 and 12 months and emerged as statistically significant mediators of treatment effects on PA across delivery channels ( ps < .014 ) . Cognitive processes , self-efficacy , decisional balance , and social support for PA participation satisfied Action Theory tests at both 6 and 12 months , but failed conceptual theory tests . Delayed intervention effects were observed on other aspects of exercise-induced feelings , PA enjoyment , and outcome expectancies , but these variables failed mediation testing at 12 months . CONCLUSION Findings are consistent with previous research illustrating the importance of behavioral processes of change , but also indicate that affective response to PA may warrant more attention as a potential target of behavior change programs The aim of this study was to evaluate the effectiveness of a computer-tailored physical activity intervention delivered through the Internet in a real-life setting . Healthy adults ( n=526 ) , recruited in six worksites , between 25 and 55 years of age were r and omized to one of three conditions receiving , respectively , ( i ) online-tailored physical activity advice + stage-based reinforcement e-mails , ( ii ) online-tailored physical activity advice only , ( iii ) online non-tailored st and ard physical activity advice . At 6-month follow-up , no differences in physical activity between study conditions were found ; total physical activity , physical activity at moderate intensity and physical activity in leisure time significantly increased in all study conditions between baseline and follow-up . Further evaluation of the intervention material s showed that the tailored advice was more read , printed and discussed with others than the st and ard advice . Most of the respondents in the e-mail group indicated to be satisfied about the number , frequency and usefulness of the stage-based e-mails . In conclusion , although tailored advice was appreciated more than st and ard advice , no evidence was found that an online-tailored physical activity intervention program outperformed online st and ard information Background Physical inactivity is an independent risk factor for diabetes and heart disease . There is evidence that increasing physical activity can reduce the risk of developing these chronic diseases , but less evidence about effective ways to increase adherence to physical activity . Interventions are therefore needed that produce sustained increases in adherence to physical activity , are cost-effective and improve clinical endpoints . Methods The Women 's Lifestyle Study is a two year r and omized controlled trial involving a nurse-led intervention to increase physical activity in 40–74 year old physically inactive women recruited from primary care . Baseline measures were assessed in a face-to-face interview with a primary care nurse . The intervention involved delivery of a ' Lifestyle script ' by a primary care nurse followed by telephone counselling for nine months and a face-to-face nurse visit at six months . Outcome measurements are assessed at 12 and 24 months . The primary outcome is physical activity measured using a vali date d physical activity question naire . Secondary outcomes include blood pressure , weight , waist circumference , physical fitness ( step test ) , serum HbA1c , fasting glucose , lipids , insulin , and quality of life ( SF36 ) . Costs were measured prospect ively to allow a subsequent cost-effectiveness evaluation if the trial is positive . Discussion Due to report in 2008 , the Women 's Lifestyle Study tests the effectiveness of an enhanced low-cost , evidence -based intervention in increasing physical activity , and improving cardiovascular and diabetes risk indicators over two years . If successful in demonstrating improvements in health outcomes , this r and omized controlled trial will be the first to demonstrate long-term cardiovascular and diabetes risk health benefit , in addition to improvements in physical activity , from a sustainable physical activity intervention based in primary care . Trial Registration Australian Clinical Trials Registry ( ACTR ) , ACTRN012605000490673 Background In many countries exercise prescriptions are used in an attempt to initiate a physically active lifestyle in sedentary population s. Previous studies have primarily evaluated low intensive exercise prescription interventions and found moderately positive effects on physical activity and aerobic fitness . In a highly intensive Danish exercise prescription scheme called ' Exercise on Prescription ' ( EoP ) the general practitioners can prescribe EoP to sedentary patients with lifestyle diseases . The aim of this r and omized trial is to assess the short- and long-term effects of the EoP scheme . Thus , the aim of this paper is to describe the r and omized controlled trial design ed for evaluating effectiveness of EoP , and to present results from validations of outcome measures . Methods / Design EoP involves a 16-week supervised training intervention and five counselling sessions ( health profiles ) . All patients referred to EoP were eligible for the trial and were offered participation during the baseline health profile . Comparisons between the EoP group and the control group were made at baseline , and after four and ten months . Physiological measures used were maximal oxygen uptake ( VO2max ) , glycosylated haemoglobin ( HbA1c ) , bodyweight , and BMI . Patient-reported measures used were physical activity , health-related quality of life , amount and intensity of exercise , compliance with national guidelines for physical activity , and physical fitness . The validation of the cycle ergometer test found a strong correlation between maximal work capacity and VO2max , and acceptable test-retest reliability at group level . Calibration of the HbA1c apparatus was stable over ten weeks with minimal use , and test-retest reliability was good . High agreement percents were found for test-retest reliability for the self-administered question naire . Discussion The trial is design ed to provide information about the effectiveness of the EoP scheme . The trial is part of a health technology assessment of EoP , which besides the effectiveness covers the patient perspective , the organization , and the health economy . All three methods vali date d were found useful for the EoP trial PURPOSE Given the prevalence of physical inactivity among American adults , convenient , low-cost interventions are strongly indicated . This study determined the 6- and 12-month effectiveness of telephone interventions delivered by health educators or by an automated computer system in promoting physical activity . DESIGN Initially inactive men and women age 55 years and older ( N = 218 ) in stable health participated . Participants were r and omly assigned to human advice , automated advice , or health education control . MEASURES The vali date d 7-day physical activity recall interview was used to estimate minutes of moderate to vigorous physical activity . Physical activity differences by experimental arm were verified on a r and om sub sample via accelerometry . RESULTS Using intention-to-treat analysis , at 6 months , participants in both interventions , although not differing from one another , showed significant improvements in weekly physical activity compared with controls . These differences were generally maintained at 12 months , with both intervention arms remaining above the target of 150 min per week of moderate to vigorous physical activity on average . CONCLUSION Automated telephone-linked delivery systems represent an effective alternative for delivering physical activity advice to inactive older adults There is growing interest in promoting health for people with disabilities , yet evidence regarding community-based interventions is sparse . This paper describes the design details of a r and omized controlled trial ( RCT ) that will test the effectiveness of a multi-component behaviorally based , intervention to promote exercise adoption ( over 6 months ) and maintenance ( up to one year ) among wheelchair users and includes descriptive data on participant characteristics at baseline . Participants were r and omly assigned to either a staff-supported intervention group or a self-guided comparison group . The primary study aim is to assess the effectiveness of the multi-component behaviorally based intervention for promoting physical activity adoption and maintenance . The RCT will also assess the physical and psychosocial effects of the intervention and the complex interplay of factors that influence the effectiveness of the intervention . Therefore , the primary outcome derives from participant reports of weekly exercise ( type , frequency , duration ) over 52 weeks . Secondary outcomes collected on four occasions ( baseline , 3 months , 6 months , 12 months ) included physiological outcomes ( VO(2 ) peak , strength ) , disability-related outcomes ( pain , fatigue , participation ) , and psychosocial outcomes ( exercise self-efficacy , exercise barriers , quality of life , depression , mood ) . This study will provide evidence regarding the effectiveness of a multi-component behaviorally based intervention for promoting exercise adoption among people with mobility impairments that necessitate wheelchair use BACKGROUND Little is known about factors affecting adherence to highly-structured and supervised exercise programs in older people . METHODS Healthy , inactive older ( ≥65 y ) women ( N = 30 ) were r and omized into a 1 ) higher- ( ATH-80 % VO₂peak ) ; 2 ) moderate- ( ATM-65 % VO₂peak ) intensity aerobic ; or 3 ) lower-intensity resistance ( RTL ; 50 % VO₂peak ) group . All 3 groups exercised 4 days·week⁻¹ for an average of 45 to 70 min·session⁻¹ over 9 months . Adherence ( % ) was defined as the proportion of prescribed sessions ( N = 144 ) in which subjects achieved their 1 ) prescribed heart rate ( intensity adherence ) and 2 ) their prescribed duration ( duration adherence ) . Primary determinants of adherence included prescribed intensity ( METs ) and prescribed duration ( min ) , as well as age , body composition , VO₂peak , and exercise self-efficacy score . RESULTS Intensity adherence was nearly 100 % for all 3 groups , while duration adherence was 95 % , 91 % , and 85 % in the RTL , ATH , and ATM groups , respectively . Prescribed exercise duration was the strongest determinant of duration adherence ( r = -0.72 ; P < .0001 ) , independent of prescribed METs , age , VO₂peak , and body composition . CONCLUSIONS Due to competing lifestyle dem and s , exercise intensity may be less of a factor in adherence among older women than is exercise duration Study objective : To compare health walks , a community based lay-led walking scheme versus advice only on physical activity and cardiovascular health status in middle aged adults . Design : R and omised controlled trial with one year follow up . Physical activity was measured by question naire . Other measures included attitudes to exercise , body mass index , cholesterol , aerobic capacity , and blood pressure . Setting : Primary care and community . Participants : 260 men and women aged 40–70 years , taking less than 120 minutes of moderate intensity activity per week . Main results : Seventy three per cent of people completed the trial . Of these , the proportion increasing their activity above 120 minutes of moderate intensity activity per week was 22.6 % in the advice only and 35.7 % in the health walks group at 12 months ( between group difference = 13 % ( 95 % CI 0.003 % to 25.9 % ) p=0.05 ) . Intention to treat analysis , using the last known value for missing cases , demonstrated smaller differences between the groups ( between group difference = 6 % ( 95 % CI −5 % to 16.4 % ) ) with the trend in favour of health walks . There were improvements in the total time spent and number of occasions of moderate intensity activity , and aerobic capacity , but no statistically significant differences between the groups . Other cardiovascular risk factors remained unchanged . Conclusions : There were no significant between group differences in self reported physical activity at 12 month follow up when the analysis was by intention to treat . In people who completed the trial , health walks was more effective than giving advice only in increasing moderate intensity activity above 120 minutes per week OBJECTIVE To evaluate three strategies for promoting physical activity ( PA ) in a primary care setting . METHOD Data were collected between 2002 and 2004 from 136 patients attending two general practice s in Brisbane , Australia . Inactive patients ( 50 - 70 years ) were r and omly allocated to one of three hierarchical intervention groups : the general practitioner ( GP ) group received ' brief ' advice ; the GP+ES group also received behavior change advice from an exercise scientist ( ES ) ; and the GP+ES+P group also received a pedometer . Self-reported PA and its determinants were measured at baseline and weeks 12 and 24 . Cardio-respiratory variables were measured at baseline and week 12 . RESULTS Overall , mean PA time increased by 84 and 128 min/week at weeks 12 and 24 ( p<.01 ) with no significant group differences . Small improvements in blood pressure and post-exercise heart rate were observed . At week 24 , the GP+ES+P group were more likely to report meeting PA guidelines than the GP group ( OR=2.39 95 % CI : 1.01 , 5.64 ) . CONCLUSION PA levels can be increased in mid- to older-age adults , either by brief advice from motivated GPs alone , or from collaboration between GPs and ESs . The most intense intervention ( GP+ES+P ) showed the most promising results BACKGROUND Ethnic minorities and lower-income adults have among the highest rates of obesity and lowest levels of regular physical activity ( PA ) . The Positive Action for Today 's Health ( PATH ) trial compares three communities that are r and omly assigned to different levels of an environmental intervention to improve safety and access for walking in low income communities . DESIGN AND SETTING Three communities matched on census tract information ( crime , PA , ethnic minorities , and income ) were r and omized to receive either : an intervention that combines a police-patrolled-walking program with social marketing strategies to promote PA , a police-patrolled-walking only intervention , or no-walking intervention ( general health education only ) . Measures include PA ( 7-day accelerometer estimates ) , body composition , blood pressure , psychosocial measures , and perceptions of safety and access for PA at baseline , 6 , 12 , 18 , and 24 months . INTERVENTION The police-patrolled walking plus social marketing intervention targets increasing safety ( training community leaders as walking captains , hiring off-duty police officers to patrol the walking trail , and containing stray dogs ) , increasing access for PA ( marking a walking route ) , and utilizes a social marketing campaign that targets psychosocial and environmental mediators for increasing PA . MAIN HYPOTHESES/ OUTCOMES : It is hypothesized that the police-patrolled walking plus social marketing intervention will result in greater increases in moderate-to-vigorous PA as compared to the police-patrolled-walking only or the general health intervention after 12 months and that this effect will be maintained at 18 and 24 months . CONCLUSIONS Implication s of this community-based trial are discussed PURPOSE Aging , in conjunction with decreasing physical activity , is associated with a range of health problems . Simple , low-maintenance , population -based means of promoting activity to counteract the age-associated decline are required . We therefore assessed the effect of pedometry and buddy support to increase physical activity . METHODS We undertook a clustered r and omized trial ( HKCTR-346 ) of 24 community centers involving 399 older Chinese participants ( ≥ 60 yr ) . Centers were r and omly allocated to 1 ) pedometry and buddy , 2 ) pedometry and no buddy , 3 ) no pedometry and buddy , and 4 ) no pedometry and no buddy with a 2 × 2 factorial design . The trial simultaneously tested the individual and combined effects of the interventions . The intervention groups also received monthly organized group activities to provide encouragement and support . Outcome measures were assessed at 6 and 12 months , including physical fitness and activity and cardiovascular disease risk factors ( anthropometry and blood pressure ) . RESULTS From the 24 centers , 356 volunteers ( 89.2 % ) completed the study . Those receiving the interventions had higher mean physical activity levels at 12 months of 1820 ( 95 % confidence interval ( CI ) = 1360 - 2290 ) and 1260 ( 95 % CI = 780 - 1740 ) MET·min·wk(-1 ) , respectively relative to the decrease in the control groups . The buddy peer support intervention significantly improved mean aerobic fitness ( 12 % [ 95 % CI = 4%-21 % ] ) and reduced both body fat ( -0.6 % [ 95 % CI = -1.1 % to 0.0 % ] ) and time to complete the 2.5-m get-up- and -go test ( -0.27 [ 95 % CI = -0.53 to -0.01 ] s ) . No other improvements in the cardiovascular disease risk factors were observed . The combination of motivational tools was no better than the individual interventions . CONCLUSIONS Both motivational interventions increased physical activity levels , and the buddy style improved fitness . These tools could be useful adjuncts in the prevention of obesity and age-related complications BACKGROUND Recent r and omized controlled trials indicated that exercise training for elderly significantly increased their physical fitness . However , very few studies have examined changes in physical activity after exercise training . The purpose of this study was to investigate whether six-month exercise training for older adults can increase and maintain their physical activity in daily life . METHODS Sixty-two men and women aged 60 to 81 years ( mean age 67.1 years ) , living in communities , were r and omly allocated into an exercise group ( n = 32 ) or a control group ( n = 33 ) . The intervention started in April 1998 and lasted for 25 weeks . The exercise regimen consisted of endurance training and resistance exercises in a two-hour class conducted at least twice a week . The subjects completed a physical activity diary at each pre-intervention ( March 1998 ) , post-intervention ( September 1998 ) and follow-up ( April 1999 ) measurement of physical activity . Physical activity , expressed as total daily energy expenditure , was calculated by multiplying the amount of time spent in each activity and the corresponding METs . RESULTS Total daily energy expenditure significantly increased from 40.8 kcal/kg/day to 43.5 kcal/kg/day in the exercise group ( p = 0.03 ) , but did not change in the control group . At the follow-up measurement , the mean total daily energy expenditure in the exercise group remained significantly higher , by 1.7 kcal/kg/day , than that at the pre-intervention ( p = 0.05 ) . CONCLUSIONS This r and omized controlled trial indicated that exercise training for elderly was effective in increasing physical activity in daily life Background The aim of the present research is to conduct a fully powered explanatory trial to evaluate the efficacy of a brief self-regulation intervention to increase walking . The intervention will be delivered in primary care by practice nurses ( PNs ) and Healthcare Assistants ( HCAs ) to patients for whom increasing physical activity is a particular priority . The intervention has previously demonstrated efficacy with a volunteer population , and subsequently went through an iterative process of refinement in primary care , to maximise acceptability to both providers and recipients . Methods / Design This two arm cluster r and omised controlled trial set in UK general practice s will compare two strategies for increasing walking , assessed by pedometer , over six months . Patients attending practice s r and omised to the self-regulation intervention arm will receive an intervention consisting of behaviour change techniques design ed to increase walking self-efficacy ( confidence in ability to perform the behaviour ) , and to help people translate their " good " intentions into behaviour change by making plans . Patients attending practice s r and omised to the information provision arm will receive written material s promoting walking , and a short unstructured discussion about increasing their walking . The trial will recruit 20 PN/HCAs ( 10 per arm ) , who will be trained by the research team to deliver the self-regulation intervention or information provision control intervention , to 400 patients registered at their practice s ( 20 patients per PN/HCA ) . This will provide 85 % power to detect a mean difference of five minutes/day walking between the self-regulation intervention group and the information provision control group . Secondary outcomes include health services costs , and intervention effects in sub-groups defined by age , ethnicity , gender , socio-economic status , and clinical condition . A mediation analysis will investigate the extent to which changes in constructs specified by the Theory of Planned Behaviour lead to changes in objective ly assessed walking behaviour . Discussion This trial addresses the current lack of evidence for interventions that are effective at increasing walking and that can be offered to patients in primary care . The intervention being evaluated has demonstrated efficacy , and has been through an extensive process of adaptation to ensure acceptability to both provider and recipient , thus optimising fidelity of intervention delivery and treatment receipt . It therefore provides a strong test of the hypothesis that a self-regulation intervention can help primary care patients increase their walking . Trial registration Current Controlled Trials IS RCT PURPOSE We compared the effectiveness of 2 physical activity prescriptions delivered in primary care — the st and ard time-based Green Prescription and a pedometer step-based Green Prescription — on physical activity , body mass index ( BMI ) , blood pressure , and quality of life in low-active older adults . METHODS We undertook a r and omized controlled trial involving 330 low-active older adults ( aged = 65 years ) recruited through their primary care physicians ’ patient data bases . Participants were r and omized to either the pedometer step-based Green Prescription group ( n = 165 ) or the st and ard Green Prescription group ( n = 165 ) . Both groups had a visit with the primary care practitioner and 3 telephone counseling sessions over 12 weeks aim ed at increasing physical activity . Outcomes were the changes in physical activity ( assessed with the Auckl and Heart Study Physical Activity Question naire ) , blood pressure , BMI , quality of life ( assessed with the 36-Item Short Form Health Survey ) , physical function status ( assessed with the Short Physical Performance Battery ) , and falls over a 12-month period . RESULTS Of the patients invited to participate , 57 % responded . At 12 months , leisure walking increased by 49.6 min/wk for the pedometer Green Prescription compared with 28.1 min/wk for the st and ard Green Prescription ( P=.03 ) . For both groups , there were significant increases across all physical activity domains at 3 months ( end of intervention ) that were largely maintained after 12 months of follow-up . BMI did not change in either group . Significant improvements in blood pressure were observed for both groups without any differences between them . CONCLUSIONS Pedometer use result ed in a greater increase in leisure walking without any impact on overall activity level . All participants increased physical activity , and on average , their blood pressure decreased over 12 months , although the clinical relevance is unknown OBJECTIVE Low-cost ( e.g. , computer-tailored ) interventions with sustained effects are needed to increase and maintain physical activity in older adults . This study examined the long-term efficacy of 2 computer-tailored physical activity interventions for older adults and its psychosocial and environmental mediators . METHODS A clustered r and omized controlled trial ( N = 1,971 ) was conducted that included 3 research arms : ( a ) basic computer-tailored print intervention , targeting psychosocial mediators ; ( b ) environmentally computer-tailored print intervention , targeting psychosocial and environmental mediators ; and ( c ) no-intervention control group . Interventions were developed using the intervention mapping approach and consisted of 3 computer-tailored letters delivered over 4 months . Question naires assessed the study outcomes ( i.e. , total weekly days and total weekly minutes of physical activity ) at baseline and 12 months . Potential mediators ( i.e. , awareness , attitude , self-efficacy , intention , social influence , intrinsic motivation , self-regulation , and perceived environment ) were assessed at baseline and at 3 or 6 months . RESULTS Multilevel regression analyses revealed that both interventions significantly changed total weekly days of physical activity compared with the control group , but only the environmentally computer-tailored print intervention significantly changed weekly minutes of physical activity . Multiple mediation models showed that the effects of both interventions on weekly days of physical activity were mediated by changes in awareness and intention . CONCLUSIONS Computer-tailored interventions were effective in inducing long-term behavioral changes in physical activity behavior of older adults . Awareness and intention were found to be important mediators of changing daily physical activity and should be included in future computer-tailored intervention studies OBJECTIVES To evaluate and compare the effectiveness and cost-effectiveness of a leisure centre-based exercise programme , an instructor-led walking programme and advice-only in patients referred for exercise by their GPs . DESIGN A single-centre , parallel-group , r and omised controlled trial , consisting of three arms , with the primary comparison at 6 months . SETTING Assessment s were carried out at Copthall Leisure Centre in Barnet , an outer London borough , and exercise programmes conducted there and at three other leisure centres and a variety of locations suitable for supervised walking throughout the borough . PARTICIPANTS Participants were aged between 40 and 74 years , not currently physically active and with at least one cardiovascular risk factor . INTERVENTIONS The 943 patients who agreed to participate in the trial were assessed in cohorts and r and omised to one of the following three arms : a 10-week programme of supervised exercise classes , two to three times a week in a local leisure centre ; a 10-week instructor-led walking programme , two to three times a week ; an advice-only control group who received tailored advice and information on physical activity including information on local exercise facilities . After 6 months the control group were rer and omised to one of the other trial arms . Assessment s took place before r and omisation , at 10 weeks ( in a r and om 50 % sub sample of participants ) , 6 months and 1 year in the leisure centre and walking arms . The control participants were similarly assessed up to 6 months and then reassessed at the same intervals as those initially r and omised to the leisure centre and walking groups . MAIN OUTCOME MEASURES The primary outcome measures were changes in self-reported exercise behaviour , blood pressure , total cholesterol and lipid subfractions . Secondary outcomes included changes in anthropometry , cardiorespiratory fitness , flexibility , strength and power , self-reported lifestyle behaviour , general and psychological health status , quality of life and health service usage . The costs of providing and making use of the service were quantified for economic evaluation . RESULTS There was a net increase in the proportion of participants achieving at least 150 minutes per week of at least moderate activity in the sport/leisure and walking categories in all three study groups : at 6 months , the net increases were 13.8 % in the leisure centre group , 11.1 % in the walking group and 7.5 % in the advice-only group . There were significant reductions in systolic and diastolic blood pressure in all groups at each assessment point compared with baseline . There were also significant and sustained improvements in cardiorespiratory fitness and leg extensor power , and small reductions in total and low-density lipoprotein cholesterol in all groups , but there were no consistent differences between the groups for any parameter over time . All three groups showed improvement in anxiety and mental well-being scores 6 months after the beginning of the trial . Leisure centre and walking groups maintained this improvement at 1 year . There were no differences between groups . Costs to the participants amounted to pound 100 for the leisure centre scheme and pound 84 for the walking scheme , while provider costs were pound 186 and pound 92 , respectively . Changes in overall Short Form 36 scores were small and advice only appeared the most cost-effective intervention . CONCLUSIONS The results of this trial suggest that referral for tailored advice , supported by written material s , including details of locally available facilities , supplemented by detailed assessment s may be effective in increasing physical activity . The inclusion of supervised exercise classes or walks as a formal component of the scheme may not be more effective than the provision of information about their availability . On cost-effectiveness grounds , assessment and advice alone from an exercise specialist may be appropriate to initiate action in the first instance . Subsidised schemes may be best concentrated on patients at higher absolute risk , or with specific conditions for which particular programmes may be beneficial . Walking appears to be as effective as leisure centre classes and is cheaper . Efforts should be directed towards maintenance of increased activity , with proven measures such as telephone support . Further research should include an up date d meta- analysis of published exercise interventions using the st and ardised mean difference approach The aim of the project was to reach inactive people through primary care offices and motivate them to become more active for health purpose s. Physical activity question naires based on the transtheoretical model ( TM ) of behaviour change were h and ed out to every person entering one of five primary care offices . All inactive people were entered into a r and omised controlled trial ( RCT ) . Individuals assigned to the feedback group were given feedback from their physician concerning their physical activity level . In addition , the advice plus group received further advice and stage matched leaflets and was offered a 45-min counselling session . Changes in physical activity behaviour were measured 7 weeks as well as 14 months after the intervention . Physicians and patients alike reacted positively to the project . Ninety percent of patients entering the primary care offices were willing to participate . Ninety percent of inactive people agreed to be entered into the RCT . The follow-up rate in this trial was 82 % at 14 months . At 7 weeks , 35 % of patients in the feedback group were now classified as active and 38 % of patients in the advice plus group . At 14 months , 47 % of the subjects in both groups were active . Inactive people can be reached effectively through primary care offices . Patients receiving feedback from their physician concerning their physical activity level improved their behaviour to the same extent as patients who were given further advice and written material s , and were offered a counselling session Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials . Recent empirical evidence in health care and physical activity promotion context s provides a foundation for testing the utility of a Self Determination Theory (SDT)-based exercise referral consultation . Methods / Design Design : An exploratory cluster r and omised controlled trial comparing st and ard provision exercise on prescription with a Self Determination Theory-based ( SDT ) exercise on prescription intervention . Participants : 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008 . The 13 exercise on prescription sites in Birmingham were r and omised to current practice ( n = 7 ) or to the SDT-based intervention ( n = 6 ) . Outcomes measured at 3 and 6-months : Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall ; physical health : blood pressure and weight ; health status measured using the Dartmouth CO-OP charts ; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score ; motivation and processes of change : perceptions of autonomy support from the advisor , satisfaction of the needs for competence , autonomy , and relatedness via physical activity , and motivational regulations for exercise . Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a st and ard programme and will test the underlying SDT-based process model ( perceived autonomy support , need satisfaction , motivation regulations , outcomes ) via structural equation modelling . Trial registration The trial is registered as Current Controlled trials IS RCT N07682833 OBJECTIVE Computer-tailored and Internet-based interventions to promote physical activity behavior have shown some promise , but only few have been tested among African Americans . We examined the feasibility and efficacy of three 1-year , multiple contact physical activity interventions ( Tailored Internet , Tailored Print , St and ard Internet ) in a sub sample of African American participants ( n = 38 ) enrolled in a r and omized controlled trial . MATERIAL S AND METHODS Participants r and omly assigned to Tailored Internet and Print programs received individually tailored computer expert system feedback delivered via Internet or print . Participants in the St and ard Internet program received access to six currently available physical activity Web sites . Self-reported physical activity was assessed at baseline and 6 and 12 months with the 7-Day Physical Activity Recall . RESULTS Across all participants , physical activity changed from 17.24 min/week ( st and ard deviation [ SD ] = 20.72 ) at baseline to 139.44 min/week ( SD = 99.20 ) at 6 months , to 104.26 min/week ( SD = 129.14 ) at 12 months . According to available consumer satisfaction data ( n = 30 ) , 70 % reported reading most or all of the physical activity information received by Internet or mail . Most participants described the Internet- and print-based physical activity programs as " somewhat " or " very " helpful ( 80 % ) and enjoyable ( 87 % ) . CONCLUSIONS These findings suggest that computer-tailored and Internet-based interventions are able to produce long-term increases in physical activity and associated process variables among African American participants . Future studies with larger numbers of African American participants are needed to determine which of the programs ( Tailored Print , Tailored Internet , St and ard Internet ) are more effective and what program modifications might be helpful in assisting this population in becoming more active BACKGROUND nearly 61 % of older adults do not maintain recommended exercise levels emphasising the need for interventions that promote exercise . OBJECTIVES to compare self-reported exercise behaviour and functional outcomes over 1 year across three groups of older adults : a cognitive-behavioural therapy group , an attention-control education group and a control group . DESIGN r and omised intervention . SETTING community exercise facilities . PARTICIPANTS three hundred and thirty-two older adults ( mean age = 71.8 ± 5.1 years ) . METHODS all three groups received exercise training three times per week for 2 weeks and then one time per week for 8 weeks , during which time the therapy and education groups received their interventions . Blinded data collectors measured follow-up exercise behaviour and functional outcomes at 3-month intervals . RESULTS after controlling for previous year exercise behaviour , results showed that relative to the control group , the therapy and education groups increased their strengthening exercises over time ( 0.05 and 0.06 h/week higher , respectively ) ; only the therapy group 's change was significant . Also , relative to the control group , the therapy and education groups significantly reduced their 6-min walking distances over time ( -1.6 m , P = 0.030 and -1.5 m , P = 0.026 , respectively ) . CONCLUSIONS although the therapy group increased their strength training , they reduced their 6-min walking distance Objective Swimming is often recommended in the prevention and treatment of hypertension . Few studies have investigated the effect of swimming training on blood pressure ( BP ) . Our objective was to evaluate 6 months of supervised moderate swimming or walking on BP in previously sedentary , normotensive , older women . Design Women aged 50–70 years ( n = 116 ) were r and omly assigned to a supervised 6-month swimming or walking programme . They were further r and omized to receive usual care or a behavioural intervention package . Methods Exercise comprised 3 sessions/week with a warm-up , cool down , and 30-min of moderate intensity walking or swimming . BP was recorded for 20 min supine , and 5 min st and ing . Assessment s were made at 0 and 6 months . Results At baseline , mean supine BP ( ± SD ) was 115.7 ± 1.3/66.8 ± 0.7 mmHg . Swimming improved swim distance by 78.1 m ( 29.3 % ) [ 95 % confidence interval ( CI ) ; 66.7 , 89.4 ] and walk time by 0.58 min ( 3.8 % ) ( 0.41 , 0.74 ) . Walking decreased walk time by 1.0 min ( 6.5 % ) ( 0.81 , 1.19 ) . After adjustment for initial BP , age , hypertension treatment status and change in weight , swimming increased supine and st and ing systolic BP relative to walking by 4.4 mmHg ( 1.2 , 7.5 ) ( P = 0.008 ) and 6.0 mmHg ( 2.6 , 9.5 ) ( P = 0.001 ) , respectively . Supine and st and ing diastolic BP increased by 1.4 mmHg ( −0.14 , 3.0 ) ( P = 0.07 ) and 1.8 mmHg ( −0.02 , 3.5 ) ( P = 0.05 ) , respectively . Conclusion Relative to moderately paced walking , regular swimming significantly elevates BP in previously sedentary , normotensive , older women . This finding may have important implication s for exercise prescription in older subjects BACKGROUND Physician counseling of patients to increase physical activity has had limited success in changing behavior . Providing organizational support to primary care providers and their patients may increase effectiveness . OBJECTIVE This study evaluates the effectiveness of a telephone-based intervention to increase physical activity among patients who exercised < 15 minutes daily and wanted to increase their physical activity over a 6-month period . DESIGN This was a r and omized controlled trial , conducted from 1997 to 1998 , of 316 patients aged 18 to 65 who were recruited from a mailed health risk assessment . Baseline and 6-month post-intervention telephone assessment s were conducted by telephone . SETTING One family physician 's patients in a suburban community . INTERVENTION Three sessions of telephone-delivered motivational counseling . MAIN OUTCOME MEASURES Physical activity score ( 11-item Physician-Based Assessment and Counseling for Exercise [ PACE ] ) 6 months after the intervention . RESULTS After adjusting for baseline exercise , there was a significantly higher level of self-reported exercise among individuals r and omized to the intervention at the 6-month follow-up . The mean level of activity at follow-up for the intervention group was a PACE score of 5.37 , compared to 4.98 in the control group ( p<0.05 ) . In the secondary analysis , which was limited to individuals who received the intervention , the effect was stronger ( PACE score of 5.58 compared to 4.94 , p<0.013 ) . CONCLUSIONS Patients can be recruited using a health-screening question naire to receive a telephone-delivered behavioral intervention to successfully increase their physical activity levels Background In Scotl and , older adults are a key target group for physical activity intervention due to the large proportion who are inactive . The health benefits of an active lifestyle are well established but more research is required on the most effective interventions to increase activity in older adults . The ' West End Walkers 65 + ' r and omised controlled trial aims to examine the feasibility of delivering a pedometer-based walking intervention to adults aged ≥65 years through a primary care setting and to determine the efficacy of this pilot . The study rationale , protocol and recruitment process are discussed in this paper . Methods / Design The intervention consisted of a 12-week pedometer-based graduated walking programme and physical activity consultations . Participants were r and omised into an immediate intervention group ( immediate group ) or a 12-week waiting list control group ( delayed group ) who then received the intervention . For the pilot element of this study , the primary outcome measure was pedometer step counts . Secondary outcome measures of sedentary time and physical activity ( time spent lying/sitting , st and ing or walking ; activPAL ™ monitor ) , mood ( Positive and Negative Affect Schedule ) , functional ability ( Perceived Motor-Efficacy Scale for Older Adults ) , quality of life ( Short-Form ( 36 ) Health Survey version 2 ) and loneliness ( UCLA Loneliness Scale ) were assessed . Focus groups with participants and semi-structured interviews with the research team captured their experiences of the intervention . The feasibility component of this trial examined recruitment via primary care and retention of participants , appropriateness of the intervention for older adults and the delivery of the intervention by a practice nurse . Discussion West End Walkers 65 + will determine the feasibility and pilot the efficacy of delivering a pedometer-based walking intervention through primary care to Scottish adults aged ≥65 years . The study will also examine the effect of the intervention on the well-being of participants and gain an insight into both participant and research team member experiences of the intervention . Trial registration numberIS RCT N : IS RCT OBJECTIVES We assessed the impact of existing best- practice physical activity programs for older adults on physical activity participation and health-related outcomes . METHODS We used a multisite , r and omized trial with 544 older adults ( mean age 66 years ) and measures at baseline , 5 , and 10 months to test the impact of a multiple-component physical activity program compared with results for a control group that did not participate in such a program . RESULTS For adults who participated in a multiple-component physical activity program , we found statistically significant benefits at 5 and 10 months with regard to self-efficacy for exercise adherence over time ( P < .001 ) , adherence in the face of barriers ( P = .01 ) , increased upper- and lower-body strength ( P = .02 , P = .01 ) , and exercise participation ( P = .01 ) . CONCLUSIONS Best- practice community-based physical activity programs can measurably improve aspects of functioning that are risk factors for disability among older adults . US public policy should encourage these inexpensive health promotion programs Background . Counseling sedentary primary care patients can increase physical activity , but whether this approach will increase exercise and fitness in elderly adults with chronic diseases remains to be determined . Methods . After receiving individualized nurse counseling to begin a program of walking for health , 60- to 80-year-old primary care patients were r and omized to one of three levels of telephone contacts over 10 months : ( i ) 20 nurse-initiated calls , ( ii ) 10 nurse-initiated calls plus 10 motivational calls programmed through an automated phone calling system , or ( iii ) no program-initiated phone contacts . Self-reported ( diary ) walking adherence was the primary outcome ; other activity , social support , health quality of life , and measured walking performance , mobility , and body mass index and girths were also assessed during the initiation ( months 1 - 6 ) and maintenance ( months 7 - 10 ) phases of the trial . Results . Average adherence for the 181 participants to the goal of walking at least 20 minutes on 3 or more days per week was 44 % for initiation and 42 % for maintenance . Participants receiving the combination of nurse-initiated personal and automated phone calls walked significantly more frequently than those with no phone contacts . Fitness improved in all three groups ; changes were generally correlated with self-reported walking . Having a companion was associated with more frequent walking . Perceived quality of physical and mental health did not change . Conclusions . Simple and relatively inexpensive nurse contacts can motivate elderly primary care patients to walk for exercise , and this activity is associated with measurable health benefits OBJECTIVE Fantasy realization theory ( Oettingen , 2012 ) proposes that fantasizing about a desired future or dwelling upon negative reality rarely changes behavior whereas mentally contrasting fantasy with reality can be an effective behavior change technique . This is because mental contrasting energizes people to overcome obstacles that st and in the way of their desired future . The present study tested whether mental contrasting promotes rates of physical activity among overweight , middle-aged , and low-SES men . METHOD A r and omized controlled trial was conducted with members of an angling club in the north of Engl and ( N = 467 ) . At baseline , participants completed a postal question naire that measured cognitions about physical activity . The intervention was embedded in the question naire for relevant participants . Behavior was followed up via telephone at 1 month and 7 months postbaseline . The key outcome measure was a vali date d , self-report measure of physical activity ( Godin , Jobin & Bouillon , 1986 ) taken at all three time-points . RESULTS Longitudinal , explanatory , and intention-to-treat analyses each indicated that mental contrasting was effective in enhancing rates of physical activity . Mental contrasting also aided the translation of beliefs about the value and worth of physical activity ( instrumental attitudes ) into action . CONCLUSION Mental contrasting appears to be an effective self-regulatory intervention for promoting physical activity and warrants further tests in health psychology Abstract Objective : To assess the long term effectiveness of the “ green prescription ” programme , a clinician based initiative in general practice that provides counselling on physical activity . Design : Cluster r and omised controlled trial . Practice s were r and omised before systematic screening and recruitment of patients . Setting : 42 rural and urban general practice s in one region of New Zeal and . Subjects : All sedentary 40–79 year old patients visiting their general practitioner during the study 's recruitment period . Intervention : General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations . Exercise specialists continued support by telephone and post . Control patients received usual care . Main outcome measures : Change in physical activity , quality of life ( as measured by the “ short form 36 ” ( SF-36 ) question naire ) , cardiovascular risk ( Framingham and D'Agostino equations ) , and blood pressure over a 12 month period . Results : 74 % ( 117/159 ) of general practitioners and 66 % ( 878/1322 ) of screened eligible patients participated in the study . The follow up rate was 85 % ( 750/878 ) . Mean total energy expenditure increased by 9.4 kcal/kg/week ( P=0.001 ) and leisure exercise by 2.7 kcal/kg/week ( P=0.02 ) or 34 minutes/week more in the intervention group than in the control group ( P=0.04 ) . The proportion of the intervention group undertaking 2.5 hours/week of leisure exercise increased by 9.72 % ( P=0.003 ) more than in the control group ( number needed to treat=10.3 ) . SF-36 measures of self rated “ general health , ” “ role physical , ” “ vitality , ” and “ bodily pain ” improved significantly more in the intervention group ( P<0.05 ) . A trend towards decreasing blood pressure became apparent but no significant difference in four year risk of coronary heart disease . Conclusion : Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months . What is already known on this topic Counselling patients in general practice on exercise has result ed in gains in physical fitness and activity , but no health benefits have been found What this study adds Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects The intervention may reduce blood pressure by an average of 1–2 mm Hg over 12 months No changes in the risk of coronary heart disease were observed The intervention is sustainable in usual general practice Prompting practice staff to deliver the intervention may have increased its Background Since many individuals who initiate physical activity programs are highly likely to return to a sedentary lifestyle , innovative strategies to efforts to increase the number of physically active older adults who successfully maintain beneficial levels of PA for a substantial length of time are needed . Methods / Design The Keep Active Minnesota Trial is a r and omized controlled trial of an interactive phone- and mail-based intervention to help 50–70 year old adults who have recently increased their physical activity level , maintain that activity level over a 24-month period in comparison to usual care . Baseline , 6 , 12 , and 24 month measurement occurred via phone surveys with kilocalories expended per week in total and moderate-to-vigorous physical activity ( CHAMPS Question naire ) as the primary outcome measures . Secondary outcomes include hypothesized mediators of physical activity change ( e.g. , physical activity enjoyment , self-efficacy , physical activity self-concept ) , body mass index , and depression . Seven day accelerometry data were collected on a sub- sample of participants at baseline and 24-month follow-up . Discussion The Keep Active Minnesota study offers an innovative approach to the perennial problem of physical activity relapse ; by focusing explicitly on physical activity maintenance , the intervention holds considerable promise for modifying the typical relapse curve . Moreover , if shown to be efficacious , the use of phone- and mail-based intervention delivery offers potential for widespread dissemination . Trial registration Clinical Trials.gov Identifier : NCT00283452 Objective To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period . Design R and omised controlled trial . Setting 17 primary care practice s in Wellington , New Zeal and Participants 1089 women aged 40 - 74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months . Main outcome measure Physical activity assessed at baseline and 12 and 24 months . Secondary outcomes were quality of life ( SF-36 ) , weight , waist circumference , blood pressure , concentrations of fasting serum lipids , glycated haemoglobin ( HbA1c ) , glucose , insulin , and physical fitness . Results Mean age was 58.9 ( SD 7 ) years . Trial retention rates were 93 % and 89 % at 12 and 24 months , respectively . At baseline , 10 % of intervention participants and 11 % of control participants were achieving 150 minutes of at least moderate intensity physical activity a week . At 12 months rates increased to 43 % and 30 % and at 24 months to 39.3 % and 32.8 % ( P<0.001 ) , respectively . SF-36 physical functioning ( P=0.03 ) and mental health ( P<0.05 ) scores improved more in intervention compared with control participants , but role physical scores were significantly lower ( P<0.01 ) . There were no significant differences in clinical outcomes . More falls ( P<0.001 ) and injuries ( P=0.03 ) were recorded in the intervention group . Conclusions This programme of exercise on prescription increased physical activity and quality of life over two years , although falls and injuries also increased . This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ANZCTRN012605000490673 Background Increasing prevalence of obesity and disorders associated with sedentary living constitute a major global public health problem . While previous evaluations of interventions to increase physical activity have involved communities or individuals with established disease , less attention has been given to interventions for individuals at risk of disease . Methods / design ProActive aims to evaluate the efficacy of a theoretical , evidence - and family-based intervention programme to increase physical activity in a sedentary population , defined as being at-risk through having a parental family history of diabetes . Primary care diabetes or family history registers were used to recruit 365 individuals aged 30–50 years , screened for activity level . Participants were assigned by central r and omisation to three intervention programmes : brief written advice ( comparison group ) , or a psychologically based behavioural change programme , delivered either by telephone ( distance group ) or face-to-face in the family home over one year . The protocol -driven intervention programme is delivered by trained facilitators , and aims to support increases in physical activity through the introduction and facilitation of a range of self-regulatory skills ( e.g. goal setting ) . The primary outcome is daytime energy expenditure and its ratio to resting energy expenditure , measured at baseline and one year using individually calibrated heart rate monitoring . Secondary measures include self-report of individual and family activity , psychological mediators of behaviour change , physiological and biochemical correlates , acceptability , and costs , measured at baseline , six months and one year . The primary intention to treat analysis will compare groups at one-year post r and omisation . Estimation of the impact on diabetes incidence will be modelled using data from a parallel ten-year cohort study using similar measures . Discussion ProActiveis the first efficacy trial of an intervention programme to promote physical activity in a defined high-risk group accessible through primary care . The intervention programme is based on psychological theory and evidence ; it introduces and facilitates the use of self-regulatory skills to support behaviour change and maintenance . The trial addresses a range of method ological weaknesses in the field by careful specification and quality assurance of the intervention programme , precise characterisation of participants , year-long follow-up and objective measurement of physical activity . Due to report in 2005 , ProActivewill provide estimates of the extent to which this approach could assist at-risk groups who could benefit from changes in behaviours affecting health , and inform future pragmatic trials Background Declining physical activity is associated with a rising burden of global disease . There is little evidence about effective ways to increase adherence to physical activity . Therefore , interventions are needed that produce sustained increases in adherence to physical activity and are cost-effective . The purpose is to assess the effectiveness of a primary care physical activity intervention in increasing adherence to physical activity in the general population seen in primary care . Method and design R and omized controlled trial with systematic r and om sampling . A total of 424 subjects of both sexes will participate ; all will be over the age of 18 with a low level of physical activity ( according to the International Physical Activity Question naire , IPAQ ) , self-employed and from 9 Primary Healthcare Centres ( PHC ) . They will volunteer to participate in a physical activity programme during 3 months ( 24 sessions ; 2 sessions a week , 60 minutes per session ) . Participants from each PHC will be r and omly allocated to an intervention ( IG ) and control group ( CG ) . The following parameters will be assessed pre and post intervention in both groups : ( 1 ) health-related quality of life ( SF-12 ) , ( 2 ) physical activity stage of change ( Prochaska 's stages of change ) , ( 3 ) level of physical activity ( IPAQ-short version ) , ( 4 ) change in perception of health ( vignettes from the Cooperative World Organization of National Colleges , Academies , and Academic Associations of Family Physicians , COOP/WONCA ) , ( 5 ) level of social support for the physical activity practice ( Social Support for Physical Activity Scale , SSPAS ) , and ( 6 ) control based on analysis ( HDL , LDL and glycated haemoglobin ) . Participants ' frequency of visits to the PHC will be registered over the six months before and after the programme . There will be a follow up in a face to face interview three , six and twelve months after the programme , with the reduced version of IPAQ , SF-12 , SSPAS , and Prochaska 's stages . Discussion The pilot study showed the effectiveness of an enhanced low-cost , evidence -based intervention in increased physical activity and improved social support . If successful in demonstrating long-term improvements , this r and omised controlled trial will be the first sustainable physical activity intervention based in primary care in our country to demonstrate long-term adherence to physical activity . Trial Registration A service of the U.S. National Institutes of Health . Developed by the National Library of Medicine . Clinical Trials.gov ID : NCT00714831 BACKGROUND Regular physical activity produces beneficial effects on health , but the exercise prescription needed to improve cardiovascular disease risk factors in free-living sedentary individuals remains unclear . METHODS Sedentary adults ( N = 492 , 64.0 % women ) were r and omized to 1 of 4 exercise-counseling conditions or to a physician advice comparison group . The duration ( 30 minutes ) and type ( walking ) of exercise were held constant , while exercise intensity and frequency were manipulated to form 4 exercise prescriptions : moderate intensity-low frequency , moderate intensity-high frequency ( HiF ) , hard intensity (HardI)-low frequency , and HardI-HiF. Comparison group participants received physician advice and written material s regarding recommended levels of exercise for health . Outcomes included 6- and 24-month changes in cardiorespiratory fitness ( maximum oxygen consumption ) , high-density lipoprotein cholesterol ( HDL-C ) level , and the total cholesterol-HDL-C ratio . RESULTS At 6 months , the HardI-HiF , HardI-low-frequency , and moderate-intensity-HiF conditions demonstrated significant increases in maximum oxygen consumption ( P < .01 for all ) , but only the HardI-HiF condition showed significant improvements in HDL-C level ( P < .03 ) , total cholesterol-HDL-C ratio ( P < .04 ) , and maximum oxygen consumption ( P < .01 ) compared with physician advice . At 24 months , the increases in maximum oxygen consumption remained significantly higher than baseline in the HardI-HiF , HardI-low-frequency , and moderate-intensity-HiF conditions and in the HardI-HiF group compared with physician advice ( P < .01 for all ) , but no significant effects on HDL-C level ( P = .57 ) or total cholesterol-HDL-C ratio ( P = .64 ) were observed . CONCLUSIONS Exercise counseling with a prescription for walking at either a HardI or a HiF produced significant long-term improvements in cardiorespiratory fitness . More exercise or the combination of HardI plus HiF exercise may provide additional benefits , including larger fitness changes and improved lipid profiles Background Despite the significant health benefits of regular physical activity , approximately half of American adults , particularly women and minorities , do not meet the current physical activity recommendations . Mobile phone technologies are readily available , easily accessible and may provide a potentially powerful tool for delivering physical activity interventions . However , we need to underst and how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women . The purpose of this paper is to describe the study design and protocol of the mPED ( mobile phone based physical activity education ) r and omized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions . Methods A r and omized controlled trial ( RCT ) with three arms ; 1 ) PLUS ( 3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention ) , 2 ) REGULAR ( 3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention ) , and 3 ) CONTROL ( pedometer only , but no intervention will be conducted ) . A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be r and omized into one of the three groups . The mobile phone serves as a means of delivering the physical activity intervention , setting individualized weekly physical activity goals , and providing self-monitoring ( activity diary ) , immediate feedback and social support . The mobile phone also functions as a tool for communication and real-time data capture . The primary outcome is objective ly measured physical activity . Discussion If efficacy of the intervention with a mobile phone is demonstrated , the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth . Trial Registration Clinical Background To our knowledge , no studies have aim ed at improving the PA level in south Asian immigrant men residing in Western countries , and few studies have considered the relevance of SCT constructs to the PA behaviour of this group in the long term . The observed low physical activity ( PA ) level among south Asian immigrants in Western countries may partly explain the high prevalence of cardiovascular diseases ( CVD ) and type 2 diabetes ( T2D ) in this group . We have shown previously in a r and omised controlled trial , the Physical Activity and Minority Health study ( PAMH ) that a social cognitive based intervention can beneficially influence PA level and subsequently reduce waist circumference and insulin resistance in the short-term . In an extended follow-up of the PAMH study : we aim ed 1 ) to determine if the intervention produced long-term positive effects on PA level six months after intervention ( follow-up 2 ( FU2 ) ) , and 2 ) to identify the social cognitive mediators of any intervention effects . Methods Physically inactive Pakistani immigrant men ( n = 150 ) who were free of CVD and T2D were r and omly assigned to a five months PA intervention or a control group . Six months after the intervention ended , we telephoned all those who attended FU1 and invited them for a second follow-up test ( FU2 ) ( n = 133 ) . PA was measured using ActiGraph accelerometers . Statistical differences between groups were determined by use of ANCOVA . Results Significant differences ( baseline to FU2 ) between the groups were found for all PA variables ( e.g. , total PA level , sedentary time , PA intensity ) . Support from family and outcome expectancies increased more in the intervention group compared with the control group . Self-efficacy did not differ significantly between groups . Conclusions Our results show that a multi component PA programme can increase PA over the short and long term in a group of immigrant Pakistani men . However , we could not identify the factors that mediated these changes in PA . Protocol ID07112001326 , NCT ID : BACKGROUND Despite well-known benefits of physical activity for older adults , about two thirds are underactive . Community-based programs are needed to facilitate increased physical activity . We examine the effectiveness of CHAMPS II , an inclusive , choice-based physical activity promotion program to increase lifetime physical activity levels of seniors . CHAMPS guided participants to choose activities that took into account their health , preferences , and abilities . It offered information on ways for them to exercise safely , motivate themselves , overcome barriers , and develop a balanced exercise regimen . METHODS A 1-year r and omized controlled trial was conducted with physically underactive seniors in a multispecialty group practice . Changes in self-reported physical activity by group were evaluated using ANCOVA , controlling for age and sex . RESULTS Of 173 r and omized subjects , 164 ( 95 % ) completed the trial . Subjects were aged 65 to 90 years ( M = 74 , SD = 6 ) ; 66 % were female . The intervention group increased estimated caloric expenditure by 487 calories/week in moderate ( or greater ) intensity activities ( MET > /= 3.0 ; p < .001 ) and by 687 calories/week in physical activities of any intensity ( p < .001 ) . Control group changes were negligible . Between-group analyses found that the changes were significantly different in both measures ( p values < .05 ) . Overweight persons especially benefited from this program . The program was as effective for women , older adults ( 75 + ) , and those who did not set aside time to exercise at baseline . CONCLUSIONS The program led to meaningful physical activity increases . Individually tailored programs to encourage lifestyle changes in seniors may be effective and applicable to health care and community setting Objective —To investigate the impact of a simple written prescription for physical activity given by a general practitioner and the effect of supplementing this with mailed information material s about physical activity . Methods —A controlled trial was conducted in 27 general practice s in New South Wales , Australia . Subjects were sequential routine care patients between 25 and 65 years old . Controls ( n = 386 ) were recruited first , and intervention subjects two weeks later . Intervention subjects were r and omised to receive a prescription only ( n = 380 ) or a prescription plus a mailed booklet ( n = 376 ) . Self reported physical activity levels were measured by interview at baseline , 6–10 weeks , and seven to eight months . Results —By intention to treat , the average changes in minutes of total physical activity did not differ significantly between the groups . Inactive people in the prescription plus supplementary booklet group were significantly more likely than controls to report an increase in their physical activity by at least 60 min/week after 6–10 weeks ( odds ratio 1.58 , 95 % confidence interval 1.06 to 2.35 ) . No significant short term improvements in self reported activity were shown in the prescription only group . In the supplemented group , the proportion reporting an increase in physical activity to 3344 kJ/week at 6–10 weeks was not significant , and neither intervention group showed significant increases in any of the outcome measures at seven to eight months by intention to treat . Treatment received analysis showed greater improvements in intervention groups , especially the prescription plus booklet group , in which the odds of inactive people in this group reporting increased activity became significant at seven to eight months . Conclusions —A prescription for physical activity from a general practitioner , supplemented by additional written material s , can lead to modest short term improvements in self reported physical activity levels among inactive patients . A prescription alone was found not to be effective BACKGROUND Physical activity interventions tailored to individual characteristics and delivered via print produce greater increases in activity compared with nontailored interventions and controls . Using the Internet to deliver a tailored physical activity intervention offers an alternative to print that might be available to larger population s at a lower cost . METHODS Participants ( N=249 adults ; mean [ SD ] age , 44.5 [ 9.3 ] years ; and mean [ SD ] body mass index [ calculated as weight in kilograms divided by height in meters squared ] , 29.4 [ 6.1 ] ) were r and omized to 1 of 3 physical activity interventions : ( 1 ) motivationally tailored Internet ( tailored Internet , n=81 ) , ( 2 ) motivationally tailored print ( tailored print , n=86 ) ; and ( 3 ) 6 research er-selected Web sites available to the public ( st and ard Internet , n=82 ) . Participants in the tailored Internet and tailored print arms received the same tailored intervention content . Participants were assessed at baseline and at 6 and 12 months . RESULTS At 6 months , participants in the tailored print arm reported a median of 112.5 minutes of physical activity per week , those in the tailored Internet arm reported 120.0 minutes , and those in the st and ard Internet arm reported 90.0 minutes ( P=.15 ) . At 12 months , the physical activity minutes per week were 90.0 , 90.0 , and 80.0 for those in the tailored print , tailored Internet , and st and ard Internet arms , respectively ( P=.74 ) . Results indicated no significant differences between the 3 arms . CONCLUSIONS The use of tailored Internet , tailored print , and st and ard Internet as part of a behavior change program increased physical activity behavior similarly . Because the use of the Internet was not different from the print-based intervention , this may be an opportunity to reach more sedentary adults in a more cost-effective way . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00200317 BACKGROUND In the U.S. , Latinos report particularly high levels of inactivity and related chronic illnesses and are in need of intervention . Thus , the purpose of the current study was to culturally and linguistically adapt an empirically supported , individually tailored physical activity print intervention for Latinos and then conduct an RCT of the modified program . DESIGN An RCT was conducted . SETTING / PARTICIPANTS The sample included 93 overweight/obese ( 80 % ) Latinas with low income and acculturation . INTERVENTION Data were collected in 2007 - 2008 and analyzed by intent-to-treat in 2009 . Participants were r and omly assigned to either ( 1 ) a culturally and linguistically adapted physical activity intervention ( Seamos Activas ) or ( 2 ) a wellness contact control condition . MAIN OUTCOME MEASURES Self-report physical activity , as measured pre- and post-intervention ( 6 months , 87 % retention ) by the 7-Day Physical Activity Recall . RESULTS Moderate-intensity ( or greater ) physical activity increased from an average of 16.56 minutes/week ( SD=25.76 ) at baseline to 147.27 ( SD=241.55 ) at 6 months in the intervention arm ( n=45 ) , and from 11.88 minutes/week ( SD=21.99 ) to 96.79 ( SD=118.49 ) in the wellness contact control arm ( n=48 ) . No between-group differences were seen in overall physical activity . Intervention participants reported significantly greater increases in cognitive ( F[1 , 91]=9.53 , p=0.003 ) and behavioral processes of change ( F[1 , 91]=8.37 , p=0.005 ) and available physical activity supplies and equipment at home ( F[1 , 91]=4.17 , p=0.04 ) than control participants . CONCLUSIONS Results supported the hypothesized feasibility , acceptability , and preliminary efficacy of individually tailored physical activity print interventions among Latinas . Although more research is needed to corroborate these findings , such high-reach , low-cost approaches have great potential to positively affect public health . TRIAL REGISTRATION NCT00724165 BACKGROUND The study examined the effectiveness of primary -care counseling using a 2-pronged intervention to increase physical activity ( PA ) in a southeastern US city . METHODS Two hundred thirty-seven patients were r and omly assigned to 1 of 3 groups ( experimental [ counseling and educational map ] , control group # 1 [ counseling only ] , or control # 2 [ st and ard care ] ) to identify PA differences . The experimental group received physician counseling and an educational map highlighting accessible recreational facilities within a 2-mile radius of the health center . RESULTS Patients in the experimental group increased their weekly PA in comparison with patients in the controls . Significant differences were observed for patients between groups for PA ( F = 7.648 , df 3,423 , P = .000 ) , PA x visits interaction ( F = 5.500 , df 3,423 , P = .001 ) , and the PA x group interaction ( F = 3.068 , df 6,848 , P = .006 ) . CONCLUSIONS This approach can perhaps increase the PA levels of underserved adults One fifth of Americans smoke ; many have no plans to quit . Motivational Interviewing ( MI ) is an effective approach to intervention with precontemplative smokers , yet a substantial number of healthcare practitioners lack training in this approach . Two interactive online tutorials were developed to teach practitioners to deliver brief tobacco cessation interventions grounded in the MI approach . The tutorials emphasized the unique aspects of working with precontemplative smokers , incorporating audio and video examples of best practice s , interactive exercises , targeted feedback , and practice opportunities . One hundred and fifty-two healthcare providers-in-training were r and omly assigned to use the online tutorials or to read training material that was matched for content . A virtual st and ardized patient evaluation was given before and after the training . Both groups improved their scores from pre- to posttest ; however , the tutorial group scored significantly better than the reading group at posttest . The results of this study demonstrate the promise of interactive online tutorials as an efficient and effective way to deliver clinical education Purpose . To determine the efficacy of community-based , culturally tailored exercise intervention on the moderate and vigorous physical activity and physiologic outcomes of low-income Latino women ( Latinas ) . Design . A r and omized trial contrasted safety education to an aerobic dance intervention . Setting . Interventions were held in a “ store-front ” exercise site near a community clinic . Subjects . Sedentary low-income Latinas ( N = 151 ; 18—55 years ; 70 % overweight/obese ) were recruited . Retention was 91 % for follow-up measures . Intervention . Three sessions per week of supervised aerobic dance were provided for 6 months . Controls attended 18 safety education sessions over 6 months . Measures . Physical activity and aerobic fitness ( VO2max ) were primary outcomes . Results . Participants in the exercise group reported more vigorous exercise ( p < .001 ) and walking ( p = .005 ) at post-test than controls . Aerobic dance and unsupervised activity result ed in a five-fold greater increase in relative VO2max compared with controls ( p < .001 ) . Although exercise and fitness decreased at follow-up , vigorous exercise ( p = .001 ) and relative VO2max ( p < .001 ) remained higher in the exercise group , suggesting maintenance at 1 year . Conclusion . Culturally tailored aerobic dance can increase vigorous physical activity , possibly generalizing to walking , and the combination can improve cardiorespiratory fitness in low-income , overweight , sedentary Latinas OBJECTIVE To enhance a previously efficacious individually tailored physical activity ( PA ) promotion intervention by adding theoretical constructs to the tailored feedback . DESIGN We r and omly assigned 248 healthy , underactive ( moderate to vigorous physical activity [ MVPA ] min/week < 90 ) adults ( mean age = 48.8 years , SD = 10.0 ) to receive either ( a ) a theoretically tailored ( based on 5 constructs from the transtheoretical model and social-cognitive theory [ SCT ] ) print-based PA promotion intervention ( print ) or ( b ) the same theoretically tailored print-based PA promotion intervention plus enhanced tailoring addressing 5 additional SCT constructs ( enhanced print ) . MAIN OUTCOME MEASURE The 7-day physical activity recall administered at baseline , Month 6 , and Month 12 , with outcomes operationalized as percentage achieving 150 min/week of MVPA . RESULTS When controlling for covariates , there was a nonsignificant trend in favor of the enhanced print condition reflecting 46 % and 50 % greater odds of achieving 150 min/week of MVPA at Month 6 and Month 12 , respectively . CONCLUSION Enhanced tailoring based on additional theoretical constructs may result in marginal improvements in physical activity outcomes INTRODUCTION Impact exercise is known to be beneficial for bones , but information regarding its effects on other health aspects is scarce . The aim of this study was to assess the effects of high-impact exercise on physical performance and glucose and lipid profiles . METHODS We performed a 12-month , population -based , r and omized controlled trial with 120 women ( 60 in the exercise group and 60 in the control group ; ages 35 - 40 yr ) . The exercise regimen comprised supervised , progressive , high-impact exercises two to three times per week and an additional home program . Physical activity was continuously recorded using an accelerometer-based method and was analyzed as the daily number of impacts within five acceleration ranges between 0.3 and 9.2 g ( g = acceleration of gravity : 9.81 m x s(-2 ) ) . The changes in physical performance and in glucose and lipid profiles were determined . RESULTS Thirty-nine women in the exercise group and 41 women in the control group completed the study . Maximal oxygen uptake ( 6.2 vs 3.1 mL x kg(-1 ) x min(-1 ) ; P = 0.008 ) and countermovement ( 2.3 vs -0.3 cm ; P < 0.001 ) and static ( 1.4 vs -0.3 cm ; P = 0.004 ) jump heights increased significantly more in the exercise group than in the control group . Exercise training also decreased waist ( -1.1 vs 0.9 cm ; P = 0.048 ) and hip circumference ( -1.0 vs 1.1 cm ; P = 0.037 ) . Total cholesterol and LDL cholesterol decreased significantly more in women , with the highest number of impacts compared with the lowest quartile at intensities exceeding 1.1 g , with differences being up to -0.5 mM ( P = 0.005 ) . Additionally , poor baseline values predicted greater exercise effects . CONCLUSION The moderate-intensity exercise regimen , initially targeted at weight-bearing bones , improved cardiorespiratory fitness , speed-strength , and lipid profiles . In addition to bone health , impact exercise may be recommended for prevention of cardiovascular diseases OBJECTIVE To examine if a website-delivered physical activity intervention , that provides participants with computer-tailored feedback , can improve physical activity in the general population . METHODS Healthy adults ( n=434 ) , recruited from parents and staff of 14 primary and secondary schools in Belgium in the spring of 2005 , were allocated into one of two intervention groups ( receiving intervention with or without repeated feedback ) or a no-intervention control group . Physical activity-levels were self-reported at baseline and at 6 months ( n=285 ) , using a computerized long version of the International Physical Activity Question naire online . Repeated measures analysis of co-variances were used to examine differences between the three groups . RESULTS Intent-to-treat analysis showed significant time by group interaction effects in favor of both intervention groups compared with the control group . Significant increases were found for active transportation ( + 20 , + 24 , + 11 min/week respectively ) and leisure-time physical activity ( + 26 , + 19 , -4 min/week respectively ) ; a significant decrease for minutes sitting on weekdays ( -22 , -34 , + 4 min/day respectively ) . No significant differences were found between both intervention groups . CONCLUSION A website-delivered intervention , including computer-tailoring , was able to increase physical activity when compared to a no-intervention control group . High drop-out rate and the low number of participants who received repeated feedback indicated that engagement and retention are important challenges in e-health studies BACKGROUND There is increasing interest in developing interventions to promote physical activity ( PA ) that do not involve face-to-face contact with health professionals . We developed a fully automated PA counseling system ( telephone-linked communication , TLC-PA ) that was delivered via telephone . DESIGN A r and omized , controlled trial with 298 adult , sedentary members ( mean age , 45.9 years ; 72 % women ; 45 % white ; and 45 % African American ) of a multi-site medical practice . The comparison group ( TLC-Eat ) received an automated intervention promoting healthy eating , which was also delivered via telephone . INTERVENTION The TLC-PA promoted moderate-intensity PA ( MI-PA ) based on the transtheoretical model of behavior change and social cognitive theory . The system was available to participants for 6 months . MAIN OUTCOMES Energy expenditure in MI-PA , proportion of participants who met recommendations for MI-PA , and motivational readiness for PA . MEASURES Self-reports of PA behavior and motivational readiness at baseline , 3 months , and 6 months . RESULTS At 3 months , intention-to-treat analyses showed that the TLC-PA group was more likely to meet recommendations for MI- or vigorous-intensity PA ( VI-PA ) compared to the TLC-Eat group ( TLC-PA=26 % vs TLC-Eat=19.6 % , p=0.04 ) . Among study completers , TLC-PA subjects reported significantly higher daily kilocalorie energy expenditure in MI-PA ( 2.3 kcal/kg/d vs 2.0 kcal/kg/d , p=0.02 ) ; a larger proportion met recommendations for MI- or VI-PA ( 31.2 % vs 21.3 % , p=0.02 ) and were in more advanced stages of motivational readiness than TLC-Eat subjects ( TLC-PA=52.5 % vs TLC-Eat=42.2 % , p=0.04 ) . Results were not maintained at 6 months . The proportion of TLC-PA users decreased significantly over the intervention period . CONCLUSIONS A fully automated counseling system had positive short-term effects on PA among sedentary adults . Lack of maintenance of effects may be due to a decrease in the number of participants who continued to use the system This article describes the equivalency testing results of a 12-week behavior change program on targeted determinates of physical activity ( PA ) and self-reported health status . Participants ( n = 192 ) were r and omized to face-to-face , combined Internet and face-to-face , and Internet-only groups . Equivalency testing was used to examine differences and statistical equivalency across groups for all outcome measures ( social support , self-efficacy , perceived health status , and motivational readiness for PA ) . Participants were assessed at baseline , postintervention , and 2 and 5 months postintervention . Motivational readiness for PA increased across all groups . The face-to-face and combined groups showed changes in social support ; however , they were not statistically different and were equivalent . There were no changes in self-efficacy or physical health status . Overall face-to-face and the Internet delivery modes show similar results . If Internet-based programs can be shown to be as effective as face-to-face , they may in turn be a more efficient and cost-effective delivery method OBJECTIVE To determine the effects of adding stages of change-based counseling to an exercise prescription for older , sedentary adults in family practice . DESIGN The Step Test Exercise Prescription Stages of change counseling study was a 12-month cluster r and omized trial . SETTING Forty family practice s in 4 regions of Canada . PARTICIPANTS Healthy , community-dwelling men ( 48 % ) and women ( 52 % ) with a mean ( SD ) age of 64.9 ( 7.1 ) years ( range 55 to 85 years ) . There were a total of 193 participants in the intervention group and 167 in the control group . INTERVENTION Intervention physicians were trained to deliver a tailored exercise prescription and a transtheoretical behaviour change counseling program . Control physicians were trained to deliver the exercise prescription alone . MAIN OUTCOME MEASURES Predicted cardiorespiratory fitness , measured by predicted maximal oxygen consumption ( pVO2max ) , and energy expenditure , measured by 7-day physical activity recall . RESULTS Mean increase in pVO2max was significant for both the intervention ( 3.02 [ 95 % confidence interval 2.40 to 3.65 ] mL/kg/min ) and control ( 2.21 [ 95 % confidence interval 1.27 to 3.15 ] mL/kg/min ) groups at 12 months ( P < .001 ) ; however , there was no difference between groups . Women in the intervention group improved their fitness significantly more than women in the control group did ( 3.20 vs 1.23 mL/kg/min ) . The intervention group had a 4-mm Hg reduction in systolic blood pressure , while the control group 's mean reduction was 0.4 mm Hg ( P < .001 ) . The mean ( SD ) energy expended significantly increased and was higher in the intervention group than in the control group ( 69.06 [ 169.87 ] kcal/d vs -6.96 [ 157.06 ] kcal/d , P < .006 ) . Practice setting characteristics did not significantly affect the primary outcomes . CONCLUSION The Step Test Exercise Prescription Stages of change exercise and behavioural intervention improved fitness and activity and lowered systolic blood pressure across a range of Canadian practice s , but this was not significantly different from the control group , which received only the exercise prescription . Women in the intervention group showed higher levels of fitness than women in the control group did ; men in both groups showed similar improvement The purpose of this paper was to report the physical activity and health outcomes results from the Physical Activity Counselling ( PAC ) trial . Patients ( n = 120 , mean age 47.3 ± 11.1 years , 69.2 % female ) who reported less than 150 min of physical activity per week were recruited from a large community-based Canadian primary care practice . After receiving brief physical activity counselling from their provider , they were r and omized to receive 6 additional patient-centered counselling sessions over 3 months from a physical activity counsellor ( intensive-counselling group ; n = 61 ) , or no further intervention ( brief-counselling group ; n = 59 ) . Physical activity ( self-reported and accelerometer ) was measured every 6 weeks up to 25 weeks ( 12 weeks postintervention ) . Quality of life was also assessed , and physical and metabolic outcomes were evaluated in a r and omly selected subset of patients ( 33 % ) . In the intent-to-treat analyses of covariance , the intensive-counselling group self-reported significantly higher levels of physical activity at 6 weeks ( p = 0.009 ) and 13 weeks ( p = 0.01 ) . There were no differences in self-reported physical activity between the groups after the intervention in the follow-up period , nor was there any increase in accelerometer-measured physical activity . Finally , the intensive-counselling patients showed greater decreases in percent body fat and total fat mass from 13 weeks to 25 weeks . Results for physical activity depended on the method used , with positive short-term results with self-report and no effects with the accelerometers . Between-group differences were found for body composition in that the intensive-counselling patients decreased more . A multisite r and omized controlled trial with a longer intensive intervention and follow-up is warranted This study compared the effects of 3 home-based exercise promotion programs for African Americans . Sixty , sedentary African-American adults were r and omly assigned to either a st and ard behavioral counseling group ( N=22 ) , a culturally sensitive counseling group ( N=20 ) , or a physician advice comparison group ( N=10 ) . The key study outcomes measured at baseline and after 6 months included cardiorespiratory fitness and physical activity . Acculturation was examined as a moderating variable . Participants in all 3 groups reported significant increases in walking , but significant improvements in fitness were observed only in the 2 intervention groups . Participants in the culturally sensitive intervention reported significantly higher levels of exercise social support compared to members of the other 2 groups . These findings show that home-based exercise counseling programs are effective for improving fitness , yet the addition of culturally tailored components may not be sufficient to produce better outcomes than st and ard behavioral counseling PURPOSE We examined the efficacy of an intervention tailored to the individual 's stage of change for exercise adoption on exercise stage of change , physical activity , and physical function in community-dwelling older adults . DESIGN AND METHODS We r and omized participants to a print and telephone intervention or a contact comparison group . Through the use of longitudinal analyses we examined the intervention 's effectiveness in promoting stage progression , altering decisional balance and the processes of change , increasing self-efficacy and physical activity , and improving physical function among older adults who completed the 24-month study ( N = 966 ) . We conducted similar analyses that excluded individuals who were in maintenance at baseline and 24 months . RESULTS At the end of the study , there were no differences in stage progression , self-efficacy , decisional balance , the processes of change , physical activity , or physical function by intervention assignment . When the analyses excluded those participants ( n = 358 ) who were in the maintenance stage for exercise throughout the intervention , we found that , compared with the comparison group , a greater proportion of individuals who received the exercise intervention progressed in stage by 24 months . Conversely , more individuals in the comparison group remained stable or regressed in stage compared with the intervention group . IMPLICATION S Results indicate that a tailored intervention is effective in increasing motivational readiness for exercise in individuals who were in stages of change other than maintenance OBJECTIVES To examine the effectiveness of prescription-based counseling and self-monitoring in the promotion of physical activity in primary health care . METHODS The study was conducted in Finl and during 2003 - 2004 . Physicians from 24 health care units ( N = 67 ) were r and omized to a prescription or a non-prescription group . The patients ( N = 265 ) were assigned to the groups according to their physician . Every other patient of the non-prescription physicians received a pedometer and a physical activity log ( MON ) and feedback about their 5-day-recordings , the rest served as controls ( CON ) . PA was assessed prior and 2 and 6 months after the physician 's appointment with a question naire . RESULTS The mean increase in weekly overall physical activity at 2 months was 1.0 ( 95 % CI 0.0 to 2.0 ) session more in the prescription group than in controls . In at least moderate-intensity physical activity , the mean difference in changes was 0.8 ( 95 % CI 0.1 to 1.5 ) sessions at 2 months and 0.9 ( 95 % CI 0.2 to 1.5 ) sessions at 6 months for the favor of the prescription group . Compared to controls , self-monitoring increased the weekly duration of overall PA at 2 months on average by 217 min ( 95 % CI 23 to 411 ) . CONCLUSIONS Prescription can be recommended as a tool for primary health care physicians to promote physical activity . Self-monitoring with an expert feedback can be useful in increasing especially the weekly duration of overall physical activity in the short term The aim of this study was to assess the effects of implementation intentions on leisure-time physical activity , taking into account the stability of intention . At baseline ( T0 ) , 349 participants completed a psychosocial question naire and were r and omly assigned to implementation intention or control condition . Three months after baseline assessment ( T1 ) , participants in the experimental group were asked to plan where , when , and how they would exercise . Leisure-time physical activity was assessed 3 mo . later ( i.e. , at 6-mo . follow-up ; T2 ) . The intervention had no significant effect on physical activity at 6-mo . follow-up . However , a significant interaction of group and intention stability was observed , with the effect of the intervention on behaviour statistically significant only among those with unstable intention . Intention stability thus moderated the effect of the intervention , i.e. , the intervention was more successful among individuals who needed support to change ( unstable intenders ) BACKGROUND Pedometers have been identified as a potential motivational aid for increasing physical activity , but their efficacy has not been demonstrated in a community-based , non clinical sample . DESIGN A r and omized controlled trial was conducted from August to December 2005 . Analysis was completed in June 2006 . SETTING / PARTICIPANTS Inactive adults aged 30 - 65 years ( n=369 ) recruited from the community . INTERVENTION Comparison of a theoretically based self-help walking program ( WP ) and weekly diaries ( sent by mail ) ; the same walking program with a pedometer ( WPP ) ( also by mail ) ; and a no-treatment control group ( C ) . MEASURES Change in self-reported leisure time in any sports/recreation in the last 3 months , and all- purpose walking ( APW ) for exercise , recreation , and travel , and other moderate , vigorous physical activity in the last week . Proportions meeting physical activity recommendations ( equal to or greater than 150 minutes and equal to or greater than five sessions/week(-1 ) ) were determined . RESULTS A 3-month follow-up interview was conducted with 314 ( 85 % ) participants . Intention-to-treat analyses indicated significance within-group increases of APW and leisure-time walking ( LTW ) , but mean and median sessions and minutes changes were greatest in the WPP group . There were no significant between-group differences in regular LTW ( walked equal to or greater than 5 sessions/week(-1 ) for at least 30 minutes/session ) , but the WPP group increased significantly participation in other sports/recreations and was more likely than the control group to meet physical activity recommendations by all leisure-time physical activity ( adjusted odds ratio=2.40 , 95 % CI=1.17 - 4.93 ) , by APW ( adjusted odds ratio=1.75 95 % CI=0.92 - 3.34 ) and all physical activity ( adjusted odds ratio=1.59 95 % CI=0.92 - 2.79 ) in the last week . CONCLUSIONS Pedometers enhanced the effects of the self-help walking program . This low-cost intervention should be tested for sustainability Background and Objective : Recommendations for physical activity to lower risk of cardiovascular disease ( CVD ) are widely known but not often followed . The purpose of this study was to determine the demographic , lifestyle , and psychosocial variables that predict improved physical activity among participants in a CVD prevention lifestyle intervention trial . Subjects and Methods : Adult family members ( N = 501 ; 66 % female ; 36 % nonwhite ; mean age , 48 years ) of cardiac patients were r and omized to a 1-year special intervention that received education on physical activity or to a control intervention . Demographics , physical activity , stage of change , and CVD risk factors were measured systematic ally at baseline and 1 year ( 94 % follow-up ) . Lipids were analyzed in a core laboratory . Linear regression models were adjusted for confounders . Results : At baseline , 21 % of participants reported exercising more than 3 d/wk , which did not differ by group assignment . The special intervention and control intervention experienced significant increases in physical activity at 1 year with mean physical activity days per week in the special intervention significantly greater than the control intervention ( 2.5 vs 2.0 d/wk , P = .03 ) . Significant predictors of increased physical activity at 1 year were group assignment ( P = .03 ) , female sex ( P = .04 ) , nonminority status ( P < .01 ) , greater readiness to change ( P < .01 ) , and baseline measurements of lower body mass index ( P < .01 ) and waist size ( P < .01 ) , greater diet adherence ( P < .01 ) , higher high-density lipoprotein cholesterol ( P < .01 ) , lower high-sensitivity C-reactive protein ( P = .02 ) , less depression ( P < .01 ) , and higher social support ( P = .03 ) . In multiple regression models , group assignment , female , and nonminority status remained independent predictors of higher physical activity levels at 1 year . Conclusion : Several predictors of improved physical activity levels at 1 year were documented among clinical trial participants . Racial/ethnic minorities and men were significantly less likely to make positive changes and may need more targeted efforts to improve physical activity levels OBJECTIVE To evaluate the effects of a lifestyle intervention and a structured exercise intervention on physical activity in older adults . METHOD Participants were r and omly assigned to a lifestyle intervention ( n=60 ) , including an individualized home-based program supported by phone calls , or to a structured intervention ( n=60 ) consisting of three weekly supervised sessions . Results were compared with a control group ( n=66 ) . Physical activity was measured with self-report question naires , pedometers , and accelerometers before the start ( pretest ) , at the end ( 11 months , posttest ) , and after 23 months ( follow-up ) . The study took place in Belgium from March 2004 until April 2006 . RESULTS At posttest , both intervention groups had significantly increased their total physical activity compared with the control group . At follow-up , the lifestyle group showed significantly larger increases in active transportation and total steps than the control and structured group respectively . There were no longer significant differences between the structured intervention and the control group . CONCLUSIONS The structured and lifestyle interventions were equally effective at the end of the intervention . One year after the intervention the lifestyle group maintained a significant increase in physical activity , which highlights the potential of lifestyle programs in the battle against inactivity in older adults There is compelling evidence supporting the benefits of increased regular physical activity in older adults . The Experience Corps program in Baltimore MD was design ed in part as a community based approach to increasing physical activity that would also appeal to older adults who have historically not utilized health promotion programs . The Baltimore Experience Corps program places older volunteers in public elementary schools for 15 h a week in roles design ed to improve the academic outcomes of children and , simultaneously , increase the physical , cognitive and social activity of volunteers . This paper reports on the change in physical activity levels among older adults associated with participation in the Baltimore Experience Corps . In a pilot r and omized controlled evaluation , older adults were r and omly assigned to Experience Corps ( EC participants ) or a waiting list control group . Ages ranged from 59–86 years , 96 % were African American , 94 % were women , and 84 % had annual incomes less than $ 15,000 . EC participants were required to serve ≥15 h a week . At follow-up after 4–8 months , an analysis of 113 r and omized volunteers revealed 53 % of the EC participants were more active than the previous year by self-report , as compared to 23 % of the controls ( p<0.01 ) . When adjusted for age , gender and education , there was a trend toward increased physical activity in the EC participants as calculated by a kilocalorie per week increase of 40 % , versus a 16 % decrease in the controls ( p=0.49 ) . EC participants who reported “ low activity ” at baseline experienced an average 110 % increase in their physical activity at follow-up . Among the controls who were in the “ low activity ” group at baseline , there was , on average , only a 12 % increase in physical activity ( p=0.03 ) . Among those who were previously active , there was no significant difference ( p=0.30 ) . The pilot results suggest that a high intensity volunteer program that is design ed as a health promotion intervention can lead , in the short-term , to significant improvements in the level of physical activity of previously inactive older adult volunteers Little research exists on the impact of behavior change interventions in disadvantaged communities . We conducted a prospect i ve study to explore the effectiveness of motivational interviewing on physical activity change within a deprived community and the social- psychological and motivational predictors of change in physical activity including stage of change , self-efficacy , social support , and variables from self-determination theory and the theory of planned behavior . Five motivational interviewing counsellors recruited 207 patients and offered motivational interviewing sessions to support physical activity behavior change . At 6-months there were significant improvements in physical activity , stage of change , and social support . A dose – response relationship was evident ; those who attended 2 or more consultations increased their total physical activity , stage of change and family social support more than those who attended just one . Hierarchical regression analyses indicated that number of sessions and change in stage of change predicted 28.4 % of the variance in change in total physical activity and , with social support from friends , 21.0 % of the variance in change walking time . Change in perceived behavioral control and attitudes , friend social support , and number of sessions predicted 16.8 % of the variance in change in vigorous physical activity . Motivational interviewing is an effective approach for promoting physical activity amongst lower socio-economic status groups in the short term . The study demonstrates good translational efficacy , and contributes to a limited number of physical activity interventions targeting low income groups in the UK OBJECTIVE Internet-based physical activity ( PA ) interventions have shown promise , although findings remain equivocal . We used formative research to enhance a previously demonstrated program ( Step into Motion ) with the goal of developing an Internet program poised for dissemination . METHODS We conducted focus groups to identify Internet features targeted to theoretical constructs ( social cognitive theory ) predictive of PA behavior and rated as " useful for increasing PA . " We identified 5 theory-targeted Internet features as useful for increasing PA : ( 1 ) a PA tracking/logging calendar targeting self-monitoring and goal setting ; ( 2 ) geographic mapping tools targeting perceived environment ; ( 3 ) a discussion forum targeting social support ; ( 4 ) exercise videos targeting observational learning ; and ( 5 ) regular up date s of peer PA progress targeting situation . We then tested the efficacy of the enhanced program ( enhanced Internet , EI ; N = 25 ) in relation to publicly available PA Websites ( st and ard Internet , SI ; N = 28 ) among 53 participants in a r and omized controlled trial . RESULTS The EI arm increased PA in relation to the SI arm at 3 months ( 18.4 to 186.0 min/wk vs. 20.9 to 57.3 min/wk ; p = .03 ) but between-groups differences were not observed at 6 months ( 176.8 vs. 133.5 min/wk ; p = .44 ) . EI participants maintained PA from 3 to 6 months ( 186.0 to 176.8 min/wk ) , and the SI group increased PA ( 57.3 to 133.5 min/wk ) . CONCLUSION The EI program was efficacious at improving PA levels in relation to publicly available Websites initially , but differences in PA levels were not maintained at 6 months . Future research should identify Internet features that promote long-term maintenance Objective : To determine whether patterns of exercise adoption by older women would conform to the Transtheoretical Model ( TTM ) of behavior change . Methods : Participants were r and omized into an exercise group ( walk 30 minutes per day , 5 days per week , plus balance exercises twice per week ) or attention control ( health education on topics other than exercise ) . The intervention was conducted over 28 weeks with 1-year follow-up . Results : Participants included 272 sedentary women aged 70 and above . Exercise adoption was higher in the intervention group ( 83 % vs. 17 % among controls ) . After 1 year , 60 % of the intervention group was in action or maintenance , compared to 16 % of the control group . Self-efficacy following the intervention predicted long-term exercise adherence . Discussion : Few studies have addressed longitudinal analysis of the TTM for exercise adoption . Most constructs from the TTM were useful in explaining exercise adoption in older sedentary women OBJECTIVES To determine the effectiveness of a behavior change intervention ( BCI ) with or without a pedometer in increasing physical activity in sedentary older women . DESIGN Prospect i ve r and omized controlled trial . SETTING Primary care , City of Dundee , Scotl and . PARTICIPANTS Two hundred four sedentary women aged 70 and older . INTERVENTIONS Six months of BCI , BCI plus pedometer ( pedometer plus ) , or usual care . MEASUREMENTS PRIMARY OUTCOME change in daily activity counts measured by accelerometry . SECONDARY OUTCOMES Short Physical Performance Battery , health-related quality of life , depression and anxiety , falls , and National Health Service re source use . RESULTS One hundred seventy-nine of 204 ( 88 % ) women completed the 6-month trial . Withdrawals were highest from the BCI group ( 15/68 ) followed by the pedometer plus group ( 8/68 ) and then the control group ( 2/64 ) . After adjustment for baseline differences , accelerometry counts increased significantly more in the BCI group at 3 months than in the control group ( P = .002 ) and the pedometer plus group ( P = .04 ) . By 6 months , accelerometry counts in both intervention groups had fallen to levels that were no longer statistically significantly different from baseline . There were no significant changes in the secondary outcomes . CONCLUSION The BCI was effective in objective ly increasing physical activity in sedentary older women . Provision of a pedometer yielded no additional benefit in physical activity , but may have motivated participants to remain in the trial RATIONALE , AIMS AND OBJECTIVES Systematic review s point to inconclusive evidence that counselling patients in a primary care setting is effective in increasing adults ' physical activity ( PA ) levels . This study evaluates the impact of an innovative physician counselling programme on physicians ' PA counselling behaviour and their patients ' PA levels . METHODS A controlled educational study conducted at six Yale School of Medicine hospitals . Sixty-five internal medicine residents and 316 primary care patients were r and omized to intervention or control groups . Intervention physicians participated in five interactive sessions outlining details of the Pressure System Model , while control physicians received usual residency training . Intervention and control patients ' PA levels and residents counselling behaviour were assessed using a vali date d question naire and compared pre- and post intervention . Data analysis was performed using paired t-tests and repeated measures anova . RESULTS At 6-month follow-up intervention , patients ' PA levels increased significantly from baseline ( 1.77 + /- 0.84 ; P = 0.0376 ) . A similar pattern was observed after 12 months ( 1.94 + /- 0.98 ; P = 0.0486 ) . Control patients ' PA did not change significantly from baseline at 6 or 12 months ( 0.35 + /- 1.00 ; P = 0.7224 and 0.99 + /- 1.52 ; P = 0.5160 , respectively ) . At 12 months , intervention residents provided PA counselling 1.5 times more than they did at baseline ( P < 0.05 ) compared with no significant changes in the control group . CONCLUSIONS The present study has shown that providing residents with a practical tool , enabling them to deal with patients ' barriers and previous failure in behavioural change , is efficacious in increasing PA levels of adult patients BACKGROUND A growing number of the population are using the Internet for health information , such as physical activity ( PA ) . The aim of this study was to examine the effectiveness of delivery modes for a behavior change program targeting PA . METHODS A r and omized trial was conducted with 192 subjects r and omly allocated to either a face-to-face , Internet-mediated , or Internet-only arm of a 12-wk intervention . Subjects included inactive adults with Internet access . The primary outcome variable was self-reported PA , assessed at four time points . RESULTS The results showed no group x time interaction for PA F(6 , 567 ) = 1.64 , p > 0.05 , and no main effect for group F(2 , 189 ) = 1.58 , p > 0.05 . However , a main effect for time F(3 , 567 ) = 75.7 , p < 0.01 was observed for each group . All groups were statistically equivalent immediately post-intervention ( p < 0.05 ) , but not at the follow-up time points ( p > 0.05 ) . The Internet-mediated and Internet-only groups showed similar increases in PA to the face-to-face group immediately post-intervention . CONCLUSIONS This study provides evidence in support of the Internet in the delivery of PA interventions and highlights avenues for future research OBJECTIVE To examine in previously sedentary older women the effects of exercise mode and a behavioural intervention on short and long-term retention and adherence . METHODS Healthy , sedentary women aged 50 - 70 years ( N=116 ) were r and omly assigned to a supervised 6-month swimming or walking program 3 sessions a week . They were further r and omised to usual care or a behavioural intervention . The same program was further continued unsupervised for 6 months . We assessed retention , adherence , stage of exercise behaviour and changes in fitness . RESULTS One hundred women ( 86 % ) completed 6 months and 86 ( 74 % ) continued for 12 months . Retention rates were similar for both exercise modes at 6 and 12 months . Adherence to swimming or walking was similar after 6 months ( 76.3 ( 95 % CI : 69.5 , 83.1)% vs. 74.3 ( 67.7 , 80.9)% ) and 12 months ( 65.8 ( 57.9 , 73.8)% vs. 62.2 ( 54.6 , 70.0)% ) . The behavioural intervention did not enhance retention or adherence . Fitness improved for both exercise modes after 6 months and was maintained at 12 months . CONCLUSIONS Either swimming or walking programs initiated with careful supervision over 6 months result ed in similar high retention and adherence rates by highly motivated older women over 12 months . Behavioural intervention in this setting did not improve these rates further OBJECTIVE The objective was to test , in a trial cohort of sedentary adults at risk of Type 2 diabetes , whether theory of planned behaviour ( TPB ) cognitions about becoming more physically active predicted objective and self-reported activity levels and change . DESIGN Participants of a r and omized controlled trial underwent measurement at baseline , 6 and 12 months . METHODS Participants ( N= 365 , 30 - 50 years ) were recruited via their parent or family history registers at 20 general practice s in the UK . Energy expenditure was measured objective ly at baseline and 1 year . Participants completed question naires assessing physical activity and beliefs about becoming more physically active over the next year at baseline , 6 and 12 months . RESULTS Between baseline and 12 months , objective energy expenditure in the cohort increased by an average of 20 minutes of brisk walking per day . Based on the 252 participants who provided complete data , affective attitude and perceived behavioural control consistently predicted intention , but intention and perceived behavioural control failed to predict physical activity levels or change ( p-values > .05 ) . CONCLUSIONS Failure of the theory to predict behaviour and behaviour change may be due to inapplicability of the theory to this at-risk population or to trial participation and intensive measurement facilitating behaviour change without affecting measured cognitions , or lack of correspondence between cognitive and behavioural measures . A wide range of potential personal and environmental mediators should be considered when design ing physical activity interventions among at-risk groups . High- quality experimental tests of the theory are needed in clinical population OBJECTIVES To evaluate a faith-based intervention ( Sisters in Motion ) intended to increase walking in older , sedentary African-American women . DESIGN R and omized controlled trial using within-church r and omization . SETTING Three Los Angeles churches . PARTICIPANTS Sixty-two African-American women aged 60 and older who reported being active less than 30 minutes three times per week and walked less than 35,000 steps per week as measured using a baseline pedometer reading . INTERVENTION Intervention participants received a multicomponent curriculum including scripture readings , prayer , goal - setting , a community re source guide , and walking competitions . Intervention and control participants both participated in physical activity sessions . MEASUREMENTS The primary outcome was change in weekly steps walked as measured using the pedometer . Secondary outcomes included change in systolic blood pressure ( SBP ) . Outcomes were assessed at baseline and 6 months after the intervention . RESULTS Eighty-five percent of participants attended at least six of eight sessions . Intervention participants averaged 12,727 steps per week at baseline , compared with 13,089 steps in controls . Mean baseline SBP was 156 mmHg for intervention participants and 147 mmHg for controls ( P=.10 ) . At 6 months , intervention participants had increased their weekly steps by 9,883 on average , compared with an increase of 2,426 for controls ( P=.02 ) ; SBP decreased on average by 12.5 mmHg in intervention participants and only 1.5 mmHg in controls ( P=.007 ) . CONCLUSION The Sisters in Motion intervention led to an increase in walking and a decrease in SBP at 6 months . This is the first r and omized controlled trial of a faith-based physical activity program to increase physical activity in older African-American women and represents an attractive approach to stimulate lifestyle change in this population BACKGROUND Declining physical activity is associated with a rising burden of global disease . Efforts to reverse this trend have not been successful . We aim ed to assess the efficacy of a facilitated behavioural intervention to increase the physical activity of sedentary individuals at familial risk of diabetes . METHODS We enrolled 365 sedentary adults who had a parental history of type 2 diabetes . They were recruited from either diabetes or family history registers at 20 general practice clinics in the UK . Eligible participants were r and omly assigned to one of two intervention groups , or to a comparison group . All participants were posted a brief advice leaflet . One intervention group was offered a 1-year behaviour-change programme , to be delivered by trained facilitators in participants ' homes , and the other the same programme by telephone . The programme was design ed to alter behavioural determinants , as defined by the theory of planned behaviour , and to teach behaviour-change strategies . The principal outcome at 1 year was daytime physical activity , which was objective ly measured as a ratio to resting energy expenditure . Analysis was by intention to treat . This study is registered as IS RCT N61323766 . FINDINGS Of 365 patients , we analysed primary endpoints for 321 ( 88 % ) for whom we had data after 1 year of follow-up . At 1 year , the physical-activity ratio of participants who received the intervention , by either delivery route , did not differ from the ratio in those who were given a brief advice leaflet . The mean difference in daytime physical-activity ratio , adjusted for baseline , was -0.04 ( 95 % CI -0.16 to 0.08 ) . The physical-activity ratio did not differ between participants who were delivered the intervention face-to-face or by telephone ( mean difference -0.05 ; 95 % CI -0.19 to 0.10 ) . INTERPRETATION A facilitated theory-based behavioural intervention was no more effective than an advice leaflet for promotion of physical activity in an at-risk group ; therefore health-care providers should remain cautious about commissioning behavioural programmes into individual preventive health-care services AIM To assess the cost-effectiveness of the ' Green Prescription ' physical activity counselling programme in general practice . METHOD Prospect i ve cost-effectiveness study undertaken as part of a cluster r and omised controlled trial with 12-month follow-up of 878 ' less-active ' patients aged 40 - 79 years in 42 general practice s in the Waikato . The intervention was verbal advice and a written exercise prescription given by general practitioners , with telephone exercise specialist follow-up compared with usual care . Main outcome measures included cost per total and leisure-time physical activity gain from health-funders ' and societal perspectives . RESULTS Significant increases in physical activity were found in the r and omised controlled trial . Programme-cost per patient was NZ170 dollars from a funder 's perspective . The monthly cost-effectiveness ratio for total energy expenditure achieved was 11 dollars per kcal/kg/day . The incremental cost of converting one additional ' sedentary ' adult to an ' active ' state over a twelve-month period was NZ1,756 dollars in programme costs . CONCLUSION Verbal and written physical activity advice given in general practice with telephone follow-up is an inexpensive way of increasing activity for sedentary people , and has the potential to have significant economic impact through reduction in cardiovascular and other morbidity and mortality OBJECTIVE To assess the cost-effectiveness of a primary care based intervention aim ed at increasing levels of physical activity in inactive people aged 45 - 74 . METHODS A total of 714 inactive people aged 45 - 74 , taken from two west London general practice s , were r and omised into two groups . Intervention subjects were invited to a consultation with an exercise development officer , and offered a personalised 10 week programme to increase their level of regular physical activity , combining leisure centre and home based activities . Control subjects were sent information on local leisure centres . All subjects were followed up at eight months . RESULTS There was a net 10.6 % ( 95 % confidence interval 4.5 to 16.9 % ) reduction in the proportion of people classified as sedentary in the intervention group compared with the control group , eight months after the intervention . The intervention group also reported an increase in the mean number of episodes of physical activity per week , as compared with the control group ( an additional 1.52 episodes ( 95 % confidence interval 1.14 to 1.95 ) ) . The cost of moving a person out of the sedentary group was shown to be less than 650 Pounds . The cost of moving someone to the now commonly recommended level was estimated at almost 2500 Pounds . CONCLUSIONS Moderate physical activity can be successfully encouraged in previously sedentary men and women aged 45 - 74 through a primary care based intervention . The process of recruitment was the most important variable cost . A high uptake rate would maximise cost-effectiveness , and sensitivity analysis suggests that unit costs could be halved with a more effective recruitment strategy BACKGROUND AND OBJECTIVE Assessing levels and determinants of physical activity as outcome measurements might have an independent effect on participant 's physical activity behavior . The objective is to study this effect in a r and omized controlled trial ( RCT ) promoting regular physical activity in Dutch general practice . METHODS Using a Solomon four-group design , participants were r and omized twice . After r and omization to a control or intervention-condition at general practice level ( N = 29 ) , participants were r and omized to a group participating in measurements at baseline , 2 and 6 months ( 3M-group , N = 361 ) , or a group only participating in measurements at 6 months ( 1M-group , N = 356 ) . Outcome measures assessed at 6 months included : level of physical activity ( self-reported and objective ly measured with accelerometry ) , meeting ACSM/CDC guideline for regular physical activity , stage of change , and determinants of physical activity . RESULTS Follow-up data on 635 participants ( 89 % ) was collected . Statistically significant measurement effects were found for meeting the ACSM/CDC guideline ( self-reported ) , self-efficacy for resisting relapse , knowledge , and on awareness . Other outcome measures showed positive trends , except stages of change . CONCLUSION Measurements of physical activity affect participant 's physical activity behavior , possibly triggered by a raised awareness about their own physical activity level . Implication s for future research are discussed , as well as method ologic limitations of the study design OBJECTIVE Older adults have low rates of physical activity participation , but respond positively to telephone-mediated support programs . Programs are often limited by reliance on professional staff . This study tested telephone-based physical activity advice delivered by professional staff versus trained volunteer peer mentors . DESIGN A 12-month , r and omized , controlled clinical trial was executed from 2003 - 2008 . Twelve volunteer peer mentors and 181 initially inactive adults ages 50 years and older were recruited from the San Francisco Bay Area . Participants were r and omized to : ( 1 ) telephone-based physical activity advice delivered by professional staff , ( 2 ) telephone-based physical activity advice delivered by trained volunteer peers , or ( 3 ) an attention-control arm of staff-delivered telephone support for nutrition . MAIN OUTCOME MEASURES Moderate-intensity or more vigorous physical activity ( MVPA ) was assessed at baseline , 6 , and 12 months with the Community Healthy Activities Model Program for Seniors ( CHAMPS ) Question naire , with accelerometry validation ( Actigraph ) in a r and omly selected sub sample . Treatment fidelity was examined through analysis of quantity and quality of intervention delivery . RESULTS At 6 and 12 months , both physical activity arms significantly increased MVPA relative to the control arm . Both physical activity arms were comparable in quantity of intervention delivery , but peers demonstrated more versatility and comprehensiveness in quality of intervention content . CONCLUSIONS This study demonstrates that trained peer volunteers can effectively promote physical activity increases through telephone-based advice . The results support a program delivery model with good dissemination potential for a variety of community setting BACKGROUND Over the last 10 years ' exercise referral schemes ' have been popular even though the evidence for effectiveness of any one-to-one intervention in primary care is deficient . We report the results of a primary care based one-to-one intervention that compared the effect of two communication styles with a no-intervention control group on self-reported physical activity at 12 months . METHODS In all , 1658 middle-aged men and women were r and omly assigned to 30 minutes of brief negotiation or direct advice in primary care or a no-intervention control group . The main outcome was self-reported physical activity at 12 months . Secondary outcome measures included change in blood pressure and body mass index . RESULTS Intention-to-treat analysis revealed no significant differences in physical activity between groups . Brief negotiation group participants who completed the study increased their physical activity significantly more than controls . There was no change in body mass index in any group . The brief negotiation group produced a greater reduction in diastolic blood pressure than direct advice . CONCLUSION If patients whose health may benefit from increased physical activity seek advice in primary care , 20 - 30 minutes of brief negotiation to increase physical activity is probably more effective than similar attempts to persuade or coerce . However , blanket physical activity promotion in primary care is not effective . The most effective way of increasing physical activity in primary care has yet to be determined The aim of this study was to compare short- ( 0 - 4 months ) and long-term ( 0 - 10 months ) effects of high-intensive Exercise on Prescription ( EoP ) intervention ( counseling and supervised exercise ) implemented in primary healthcare in a number of Danish counties with a low-intensive intervention ( counseling ) using maximal oxygen uptake ( VO(2max ) ) as the primary outcome . The study was conducted as a r and omized trial in 2005 - 2006 with a high and a low-intensive group . All the patients referred to the EoP scheme by their GP in the counties of Vejle and Ribe , Denmark , were eligible for the trial . The high-intensive EoP group received 4 months of group-based supervised training and attended five motivational counseling sessions . The low-intensive group only attended four motivational counseling sessions . Three hundred and twenty-seven patients entered the EoP scheme , and 52 ( 16 % ) volunteered for the r and omized trial . No short- or long-term differences were found between the high and the low-intensive groups for VO(2max ) ( short-term 95 % CI -1.1 ; 4.4 mL O(2)/(kg min ) , long-term 95 % CI -1.6 to 2.1 ) . The present study did not demonstrate any significant clinical outcome for the high-intensive EoP intervention as opposed to the low-intensive intervention OBJECTIVE The research tested the efficacy of planning and partner-based interventions to promote physical activity over six months . METHOD Local government ( council ) employees ( N = 257 ) were r and omly allocated to one of four conditions ( collaborative implementation intentions ; partner-only ; implementation intentions ; control group ) before completing measures at baseline and follow-ups at 1 , 3 and 6 months . Outcome measures comprised vali date d self-report measures of physical activity : the international physical activity question naire ( IPAQ ; Craig et al. , 2003 ) and self-report walking and exercise tables ( SWET ; Prestwich et al. , 2012 ) ; psychosocial mediators ( enjoyment , intention , self-efficacy , social influence ) ; weight and waist size ( baseline and 6 months only ) . RESULTS As well as losing the most weight , there was evidence that participants in the collaborative implementation-intention group were more physically active than each of the other three groups at 1- , 3- and 6-month follow-ups . Those in the implementation-intention and partner-only conditions did not outperform the control group on most measures . CONCLUSION Collaborative implementation intentions represent a potentially useful intervention to change important health behaviors that help reduce weight Voluntary employees ( N = 155 ) from nine different companies were screened by question naire for the study . They were r and omized into three study groups : counseling ( n = 52 ) , counseling + fitness testing ( n = 51 ) and control group ( n = 52 ) . The counseling was based on a goal -oriented conversation session for each participant and three follow-up appointments with an occupational nurse over a period of 1 year . The fitness tests were adapted from the UKK Health-related Fitness Test Battery . The outcome measures were the changes in the amount of leisure-time physical activity ( LTPA ) assessed by diary , pedometer and question naire at baseline and at 6 and 12 month follow-up visits . As a result , no statistically significant differences were detected between the three groups at either of the follow-up visits . It seemed , thus , that the two PA counseling methods implemented had no direct mid- or long-term effects on the LTPA of voluntary employees with no specific disease-related indication to increase LTPA OBJECTIVES To evaluate the long-term effects of a lifestyle intervention and a structured exercise intervention on physical fitness and cardiovascular risk factors in older adults . DESIGN Controlled trial with r and omization between the intervention groups . SETTING Belgium , Vlaams-Brabant . PARTICIPANTS One hundred eighty-six sedentary but healthy men and women aged 60 to 83 . INTERVENTIONS Participants in the lifestyle intervention were stimulated to integrate physical activity into their daily routines and received an individualized home-based program supported by telephone calls . The structured intervention consisted of three weekly supervised sessions in a fitness center . Both interventions lasted 11 months and focused on endurance , strength , flexibility , and postural and balance exercises . MEASUREMENTS Cardiorespiratory fitness , muscular strength , functional performance , blood pressure , and body composition were measured before ( pretest ) , at the end ( 11 months , posttest ) , and 1 year after the end ( 23 months , follow-up ) of the interventions . RESULTS The results from pretest to posttest have already been published . The current study analyzed the results from posttest to follow-up . There was a decrease in cardiorespiratory fitness , muscular fitness , and functional performance from posttest to follow-up in the structured intervention group but not in the control group or the lifestyle intervention group . At 23 months , participants in both groups still showed improvements in cardiorespiratory fitness . In addition , the structured group showed long-term improvements in muscular fitness , whereas the lifestyle group showed long-term improvements in functional performance . No long-term effects were found for blood pressure or body composition . CONCLUSION These results highlight the potential of a structured fitness center-based intervention and a home-based lifestyle intervention in the battle against inactivity in older adults . Lifestyle programs are especially valuable because they require fewer re sources and less time from health institutions and health practitioners Objective : This study investigated the role of coping plans and the use of selection , optimisation and compensation ( SOC ) strategies within an experimental evaluation of a 26-week physical exercise intervention . Methods : Older women ( N = 86 , M age = 73.7 years ) were r and omly assigned to a telephone-assisted or a self-administered coping planning intervention after 6 weeks ’ participation in an exercise programme . The number of different coping plans formulated , exercise-specific SOC strategy use and their interaction were used to predict objective ly measured long-term adherence to the intervention . Results : The number of coping plans formulated ( β = 0.28 ) and goal -pursuit strategies reported ( sum score of optimisation and compensation strategies , β = 0.39 ) predicted adherence to the exercise programme over 20 weeks . The predictive strength of coping plans increased with decreasing numbers of goal -pursuit strategies ( β = −0.21 ) . Women supported via telephone reported significantly more coping plans than did women in the self-administered coping planning group , F(1,80 ) = 9.47 , p = 0.003 . Conclusion : Coping plans have a buffering effect on adherence levels when use of SOC strategies is low . Older women 's adherence to physical activities may be improved if they are given direct support in generating coping plans involving strategies of selection , optimisation and compensation Aim To assess the cost-effectiveness of exercise on prescription with ongoing support in general practice . Methods Prospect i ve cost-effectiveness study undertaken as part of the 2-year Women 's lifestyle study r and omised controlled trial involving 1089 ‘ less-active ’ women aged 40–74 . The ‘ enhanced Green Prescription ’ intervention included written exercise prescription and brief advice from a primary care nurse , face-to-face follow-up at 6 months , and 9 months of telephone support . The primary outcome was incremental cost of moving one ‘ less-active ’ person into the ‘ active ’ category over 24 months . Direct costs of programme delivery were recorded . Other ( indirect ) costs covered in the analyses included participant costs of exercise , costs of primary and secondary healthcare utilisation , allied health therapies and time off work ( lost productivity ) . Cost – effectiveness ratios were calculated with and without including indirect costs . Results Follow-up rates were 93 % at 12 months and 89 % at 24 months . Significant improvements in physical activity were found at 12 and 24 months ( p<0.01 ) . The exercise programme cost was New Zeal and dollars ( NZ$ ) 93.68 ( € 45.90 ) per participant . There was no significant difference in indirect costs over the course of the trial between the two groups ( rate ratios : 0.99 ( 95 % CI 0.81 to 1.2 ) at 12 months and 1.01 ( 95 % CI 0.83 to 1.23 ) at 24 months , p=0.9 ) . Cost – effectiveness ratios using programme costs were NZ$687 ( € 331 ) per person made ‘ active ’ and sustained at 12 months and NZ$1407 ( € 678 ) per person made ‘ active ’ and sustained at 24 months . Conclusions This nurse-delivered programme with ongoing support is very cost-effective and compares favourably with other primary care and community-based physical activity interventions internationally OBJECTIVES To assess the long-term effectiveness of a telephone counseling intervention on physical activity and health-related quality of life in low-active older adults recruited through their primary care physician . DESIGN R and omized , controlled trial . SETTING Three primary care practice s from different socioeconomic regions of Auckl and , New Zeal and . PARTICIPANTS One hundred and eighty-six low-active adults ( aged 65 ) recruited from their primary care physicians ' patient data bases . INTERVENTION Eight telephone counseling sessions over 12 weeks based on increasing physical activity . Control patients received usual care . MEASUREMENTS Change in physical activity ( as measured using the Auckl and Heart Study Physical Activity Question naire ) and quality of life ( as measured using the Short Form-36 Health Survey ( SF-36 ) ) over a 12-month period . RESULTS Moderate leisure physical activity increased by 86.8 min/wk more in the intervention group than in the control group ( P=.007 ) . More participants in the intervention group reached 2.5 hours of moderate or vigorous leisure physical activity per week after 12 months ( 42 % vs 23 % , odds ratio=2.9 , 95 % confidence interval=1.33 - 6.32 , P=.007 ) . No differences on SF-36 measures were observed between the groups at 12 months . CONCLUSION Telephone-based physical activity counseling is effective at increasing physical activity over 12 months in previously low-active older adults This study investigated the effectiveness of a 10-week primary care exercise referral intervention on the physical self-perceptions of 40 - 70 year olds . Participants ( N=142 ) were assessed , r and omized to an exercise or control group , and reassessed at 16 and 37 weeks . The Physical Self-Perception Profile ( PSPP ; K. R. Fox , 1990 ) , fitness , physical activity , body mass index , body fat ( skinfolds ) , and hip and waist circumference were assessed . A multivariate analysis of variance revealed significant Group X Time interactions , with the exercise group showing greater physical self-worth , physical condition , and physical health at 16 and 37 weeks . Changes in all PSPP scales at baseline and 37 weeks were related to changes in anthropometric measures and adherence to the 10-week exercise program but not to changes in submaximal fitness parameters OBJECTIVE To evaluate the use of a local neighborhood environment-focused physical activity website and its effects on walking and overall physical activity in middle-aged adults . METHOD One-hundred and six ( 72 % women ) inactive adults aged 52+/-4.6 years were r and omly allocated to receive access to a neighborhood environment-focused website , ( Neighborhood group , n=52 ) or a motivational-information website ( Comparison group n=54 ) . Participants also received eleven emails over the 26 weeks . Study outcomes were objective ly-monitored website use , and self-reported total walking ( min/wk ) , total physical activity ( min/wk ) and neighborhood walking ( min/wk ) collected at baseline , 12 and 26 weeks . The study was conducted between August 2005 and February 2006 in Brisbane , Australia . RESULTS Website use was significantly greater among Neighborhood participants ( p=0.01 ) . Statistically significant increases in walking and total physical activity were observed in both groups . There was also a statistically significant interaction effect for total physical activity , with Neighborhood group participants maintaining more of their initial increase in physical activity at week-26 ( p<0.05 ) . Further , those in the Neighborhood group who used the website more often reported significantly more walking along the community trail at week-26 ( p=0.05 ) compared with those who did not . CONCLUSIONS A local neighborhood-environment focused physical activity website was more effective at engaging participants than a motivational-information website . Moreover , its use result ed in meaningful increases in physical activity relative to the comparison website To compare the effects of a pedometer-based behavioral intervention ( Fitness for Life [ FFL ] program ) and a traditional high-intensity fitness ( TRAD ) program on physical activity ( PA ) , Army Physical Fitness Test ( APFT ) , and coronary heart disease risk factors in Army National Guard members who failed the APFT 2-mile run . From a pool of 261 Army National Guard , a total of 156 were r and omized to TRAD or FFL for 24 weeks consisting of a 12-week progressive conditioning program followed by 12 weeks of maintenance . For both groups , the total APFT score and 2-mile run time/score improved from baseline to 12 weeks ( FFL : down 7.4 % , p = 0.03 ; TRAD : down 5 % , p = 0.08 ) but at 24 weeks they had regressed toward baseline . PA improved modestly and coronary risk profile changed minimally in both groups . A pedometer-based exercise intervention had results similar to a high-intensity program for improving PA , APFT , and 2-mile run times/score . Neither group sustained the improved run times over the 12 weeks of maintenance Primary care is a promising venue to build patient motivation and confidence to increase physical activity ( PA ) . Physician PA counselling has demonstrated some success ; however , maintenance of behaviour change appears to require more intensive interventions . In reality , most physicians do not have the necessary training nor the time for this type of counselling . The purpose of this paper is to outline the rationale , methods , and interventions for the ongoing physical activity counselling ( PAC ) r and omized controlled trial ( RCT ) , which aims to assess the impact of integrating a PA counsellor into a primary care practice . This RCT has 2 arms : ( i ) brief PA counselling ( 2 - 4 min ) from a health care provider and ( ii ) brief PA counselling+intensive PA counselling from a PA counsellor ( 3 months ) . The impact of this intervention is being evaluated using the comprehensive RE- AIM framework . One hundred twenty insufficiently active adult patients , aged 18 to 69 y and recruited during regular primary care visits have been r and omized . Dependent measures include psychological mediators , PA participation , quality of life , and physical and metabolic outcomes . The PAC project represents an innovative , theoretically-based approach to promoting PA in primary care , focusing on psychological mediators of change . We anticipate that key lessons from this study will be useful for shaping future public health interventions , theories , and research BACKGROUND Perceptions of personal efficacy have been consistently identified as being determinants of exercise adherence in asymptomatic , rehabilitative , younger , and older population s. The present study incorporated a r and omized control design in an effort to examine the effects of an efficacy-based intervention in enhancing exercise adherence in a large sample ( N = 114 ) of formerly sedentary middle-aged males and females . METHODS Subjects r and omly assigned to an exercise plus intervention group or an exercise plus attentional control group participated in a 5-month long walking program led by trained personnel . Exercise behavior ( frequency , miles walked , duration ) were assessed on a continuous basis and self-efficacy was measured at 1 , 2 , and 4 months . RESULTS Repeated measures multivariate analyses revealed a significant treatment effect with subjects in the intervention group exercising more frequently , for longer duration , and walking greater distances over the course of the program . Path analysis indicated that the effect of the treatment on adherence was direct rather than through self-efficacy as hypothesized . Self-efficacy was , however , a significant predictor of exercise behavior in the early and middle stages of the exercise program but not during the last month . CONCLUSIONS An intervention program design ed to maximize information pertaining to participants ' capabilities appears to have had a reasonable effect on reducing attrition in middle-aged males and females and self-efficacy was a significant predictor of exercise frequency over time . Further research efforts are required to tease out those cognitive factors that might underlie any effects of interventions in exercise adherence OBJECTIVE Given that only 25 % of Americans meet physical activity recommendations , there is a need to develop and disseminate effective , evidence -based interventions to promote physical activity . The authors tested 2 delivery channels , telephone and print , to determine whether one was more effective in promoting physical activity . DESIGN The authors r and omly assigned 239 healthy , sedentary adults to ( a ) telephone-based individualized feedback , ( b ) print-based individualized feedback , or ( c ) contact control . Both intervention arms were guided by a motivationally tailored , theoretically driven computer expert system . MAIN OUTCOME MEASURES Physical activity as measured by the 7-day Physical Activity Recall interview . RESULTS At 6 months , both telephone and print arms significantly increased in minutes of moderate intensity physical activity compared with control , with no differences between the intervention arms . At 12 months , print participants reported a significantly greater number of moderate intensity minutes than both telephone and control participants , who did not differ . CONCLUSION Results suggest that both telephone and print enhance the adoption of physical activity among sedentary adults ; however , print interventions may be particularly effective in maintaining physical activity in the longer term The objectives were to investigate in older adults ( 1 ) whether regular preventive home visits are associated with change or stability in physical activity and ( 2 ) whether education of home visitors influences stability and change in physical activity . The design was a prospect i ve controlled r and omised follow-up study with r and omization at municipality level ( 17 intervention and 17 control municipalities ) and outcomes measured at individual level . Visitors in the intervention-municipalities received regular education during 3 years . The effect of the intervention was measured by a question naire survey among 1,913 old persons living in the 34 municipalities at baseline and 4½-year follow-up . Changes in physical activity were measured through self-reported frequencies of vigorous physical activity . All logistic regression analyses were stratified by sex and age group ( 75 and 80 years old ) . There was no effect of receiving preventive home visits on change in physical activity among the men and among the 75-year-old women . Among the physically active 80-year-old women those who accepted and received more than four preventive home visits were more likely to go on being physically active compared to women who did not receive preventive home visits . Among the sedentary 80-year-old women those living in the intervention municipalities tended to increase their physical activity compared to the control women . These results were not seen in the old men . Preventive home visits as part of daily routine in primary care and education of home visitors and general practitioners may promote physical activity in older women BACKGROUND Faith-based interventions using a community-based participatory approach hold promise for eliminating ethnic health disparities . This study evaluated the effects of a volunteer-led statewide program to increase physical activity among members of African-American churches . METHODS African Method ist Episcopal churches within six regions ( Conferences ) were r and omly assigned to receive training in the program immediately or 1 year later . A cohort of 20 r and omly selected churches and 571 members within them took part in telephone surveys at baseline ( May-September 2003 ) and 1 year ( May-August 2004 ) and 2 years later ( June-September 2005 ) . Primary outcomes were physical activity participation , meeting physical activity recommendations , and stage of readiness for physical activity change . Statistical analyses were completed in April 2006 . RESULTS Volunteers ( N=889 ) from 303 churches were trained . Among survey respondents , physical activity did not increase significantly over time , although 67 % were aware of the program . Program awareness was significantly related to all three physical activity outcomes and to fruit and vegetable consumption . Pastoral support was significantly associated with physical activity . CONCLUSIONS Although this intervention reached a large number of churches and created awareness of intervention components , no effects on physical activity behaviors were found . Potential reasons for the lack of significant effects are discussed The health effects of increased physical activity in the prevention or treatment of any disease can only be meaningfully assessed if compliance to the exercise regimen is maintained . The current research examined compliance in a clinical trial investigating the effect of walking on bone loss in 229 postmenopausal women , r and omized into either a walking or a control group . Although at baseline there was no difference in physical activity between the two groups , after a period of 2 yr , the walking group reported significantly greater physical activity as measured by reported mean blocks walked daily and objective activity monitor day readings . Closer examination of the walking group revealed that compliers ( average 7 + miles walked/wk over the 2 yr ) , when compared to non-compliers , tended at baseline to be more active , lighter weight , and non-smokers . However , the variable that best differentiated between the two compliance groups was the frequency of reported illness over the 2-yr period , with compliers cl aim ing significantly less illness Background Web-based interventions are popular for promoting healthy lifestyles such as physical activity . However , little is known about user characteristics , adherence , attrition , and predictors of repeated participation on open access physical activity websites . Objective The focus of this study was Active-online , a Web-based individually tailored physical activity intervention . The aims were ( 1 ) to assess and compare user characteristics and adherence to the website ( a ) in the open access context over time from 2003 to 2009 , and ( b ) between trial participants and open access users ; and ( 2 ) to analyze attrition and predictors of repeated use among participants in a r and omized controlled trial compared with registered open access users . Methods Data routinely recorded in the Active-online user data base were used . Adherence was defined as : the number of pages viewed , the proportion of visits during which a tailored module was begun , the proportion of visits during which tailored feedback was received , and the time spent in the tailored modules . Adherence was analyzed according to six one-year periods ( 2003 - 2009 ) and according to the context ( trial or open access ) based on first visits and longest visits . Attrition and predictors of repeated participation were compared between trial participants and open access users . Results The number of recorded visits per year on Active-online decreased from 42,626 in 2003 - 2004 to 8343 in 2008 - 2009 ( each of six one-year time periods ran from April 23 to April 22 of the following year ) . The mean age of users was between 38.4 and 43.1 years in all time periods and both context s. The proportion of women increased from 49.5 % in 2003 - 2004 to 61.3 % in 2008 - 2009 ( P < .001 ) . There were differences but no consistent time trends in adherence to Active-online . The mean age of trial participants was 43.1 years , and 74.9 % were women . Comparing context s , adherence was highest for registered open access users . For open access users , adherence was similar during the first and the longest visits ; for trial participants , adherence was lower during the first visits and higher during the longest visits . Of registered open access users and trial participants , 25.8 % and 67.3 % respectively visited Active-online repeatedly ( P < .001 ) . Predictors of repeated use were male sex ( odds ratio [ OR ] = 1.2 , 95 % confidence interval [ CI ] = 1.04 - 1.38 ) and increasing age category in registered open access users , and age 46 - 60 versus < 30 years ( OR = 3.04 , 95 % CI = 1.25 - 7.38 ) and Swiss nationality ( ORnonSwiss= 0.64 , 95 % CI = 0.41 - 1.00 ) in trial participants . Despite reminder emails , attrition was much higher in registered open access users compared with trial participants , with a median lifetime website usage of 0 days in open access users and 290 days in trial participants . Conclusions Adherence , patterns of use , attrition , and repeated participation differed between trial participants and open access users . Reminder emails to encourage repeated participation were effective for trial participants but not for registered open access users . These issues are important when interpreting results of r and omized controlled effectiveness trials The aim of this study was to explore the feasibility of an exercise scientist ( ES ) working in general practice to promote physical activity ( PA ) to 55 to 70 year old adults . Participants were r and omised into one of three groups : either brief verbal and written advice from a general practitioner ( GP ) ( G1 , N=9 ) : or individualised counselling and follow-up telephone calls from an ES , either with ( G3 , N=8 ) or without a pedometer ( G2 , N=11 ) . PA levels were assessed at week 1 , after the 12-wk intervention and again at 24 weeks . After the 12-wk intervention , the average increase in PA was 116 ( SD=237 ) min/wk : N=28 , p<0.001 . Although there were no statistically significant between-group differences , the average increases in PA among G2 and G3 participants were 195 ( SD=207 ) and 138 ( SD=315 ) min/wk respectively , compared with no change ( 0.36 , SD=157 ) in G1 . After 24 weeks , average PA levels remained 56 ( SD=129 ) min/wk higher than in week 1 . The small numbers of participants in this feasibility study limit the power to detect significant differences between groups , but it would appear that individualised counselling and follow-up contact from an ES , with or without a pedometer , can result in substantial changes in PA levels . A larger study is now planned to confirm these findings OBJECTIVES To build upon state-of-the-art theory and empirical data to estimate the strength of multiple mediators of the efficacious Keep Active Minnesota ( KAM ) physical activity ( PA ) maintenance intervention . METHODS The total , direct , and indirect effects through which KAM helped r and omized participants ( KAM n = 523 ; UC n = 526 ) maintain moderate or vigorous PA ( MVPA ) for up to 2 years were estimated using structural equation modeling . RESULTS Multiple mediators explained half ( beta = .052 , P = .13 ) of the effect of KAM on MVPA ( beta = .105 , P = .004 ) . Self-efficacy was the upstream variable in 2 endogenously mediated effects , and the self-concept mediator emerged as the strongest predictor of MVPA . CONCLUSIONS KAM positively impacted self-efficacy , which was associated with PA enjoyment , integration into the self-concept , and PA maintenance . Successful long-term PA maintenance appears to be influenced by multiple small interrelated mediational pathways . Future research evaluating maintenance models should specify recursive relationships among mediators and outcomes BACKGROUND Given the low rates of physical activity participation , innovative intervention approaches are needed to make a public health impact . METHODS The study was conducted at the Miriam Hospital/Brown Medical School in Providence , RI , and in communities of Southeastern Massachusetts from 2002 to 2005 . Previously sedentary women ( n = 280 ; mean age = 47.1 ; 94.6 % Caucasian ) were r and omly assigned to one of three conditions : ( 1 ) Choose to Move , a self-help printed booklet ( n = 93 ) , ( 2 ) Jumpstart , a motivationally tailored , print based intervention ( n = 95 ) ; or ( 3 ) Wellness , women 's health material s ( n = 92 ) . Face-to-face contact at months 3 ( M3 ) and 12 ( M12 ) occurred within participants ' communities in local libraries . RESULTS At M3 , participants in the Jumpstart condition reported significantly more minutes of physical activity per week ( M = 140.4 , SE = 14.82 ) than participants in the Wellness condition ( M = 98.1 , SE = 15.09 ) , ( t(275 ) = 2.00 , p < 0.05 ) . The Jumpstart arm showed a trend towards significance ( t(275 ) = 1.93 , p = 0.054 ) when compared with the CTM arm ( M = 99.5 , SE = 15.11 ) ; there was no significant difference between the CTM and Wellness arms ( t(275 ) = 0.07 , p = NS ) . At M12 , there were no significant differences ( F(2,275 ) = 0.147 , p = NS ) between any of the treatment arms . CONCLUSIONS Results suggest that print-based programs for physical activity may be efficacious short-term , but more research is needed to find approaches that are effective long-term . It is possible to deliver print-based programs through existing community infrastructures , however these approaches need further evaluation to examine maintenance effects apart from the dem and characteristics of a research study Background The Active Plus project is a systematic ally developed theory- and evidence -based , computer-tailored intervention , which was found to be effective in changing physical activity behavior in people aged over 50 years . The process and effect outcomes of the first version of the Active Plus project were translated into an adapted intervention using the RE- AIM framework . The RE- AIM model is often used to evaluate the potential public health impact of an intervention and distinguishes five dimensions : reach , effectiveness , adoption , implementation , and maintenance . Objective To gain insight into the systematic translation of the first print-delivered version of the Active Plus project into an adapted ( Web-based ) follow-up project . The focus of this study was on the reach and effectiveness dimensions , since these dimensions are most influenced by the results from the original Active Plus project . Methods We optimized the potential reach and effect of the interventions by extending the delivery mode of the print-delivered intervention into an additional Web-based intervention . The interventions were adapted based on results of the process evaluation , analyses of effects within subgroups , and evaluation of the working mechanisms of the original intervention . We pretested the new intervention material s and the Web-based versions of the interventions . Subsequently , the new intervention conditions were implemented in a clustered r and omized controlled trial . Results Adaptations result ed in four improved tailoring interventions : ( 1 ) a basic print-delivered intervention , ( 2 ) a basic Web-based intervention , ( 3 ) a print-delivered intervention with an additional environmental component , and ( 4 ) a Web-based version with an additional environmental component . Pretest results with participants showed that all new intervention material s had modest usability and relatively high appreciation , and that filling in an online question naire and performing the online tasks was not problematic . We used the pretest results to improve the usability of the different interventions . Implementation of the new interventions in a clustered r and omized controlled trial showed that the print-delivered interventions had a higher response rate than the Web-based interventions . Participants of both low and high socioeconomic status were reached by both print-delivered and Web-based interventions . Conclusions Translation of the ( process ) evaluation of an effective intervention into an adapted intervention is challenging and rarely reported . We discuss several major lessons learned from our experience . Trial Registration Nederl and s Trial Register ( NTR ) : 2297 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2297 ( Archived by WebCite at http://www.webcitation.org/65TkwoESp ) Brief planning interventions , usually delivered within paper and pencil question naires , have been found to be effective in changing health behaviours . Using a double-blind r and omised controlled trial , this study examined the efficacy of two types of planning interventions ( action plans and coping plans ) in increasing physical activity levels when they are delivered via the internet . Following the completion of self-reported physical activity ( primary outcome ) and theory of planned behaviour ( TPB ) measures at baseline , students ( N = 1273 ) were r and omised into one of four conditions on the basis of a 2 ( received instructions to form action plans or not ) × 2 ( received instructions to form coping plans or not ) factorial design . Physical activity ( primary outcome ) and TPB measures were completed again at two-month follow-up . An objective measure ( attendance at the university 's sports facilities ) was employed 6 weeks after a follow-up for a duration of 13 weeks ( secondary outcome ) . The interventions did not change self-reported physical activity , attendance at campus sports facilities or TPB measures . This might be due to low adherence to the intervention protocol ( ranging from 58.8 to 76.7 % ) . The results of this study suggest that the planning interventions under investigation are ineffective in changing behaviour when delivered online to a sample of participants unaware of the allocation to different conditions . Possible moderators of the effectiveness of planning interventions in changing health behaviours are discussed OBJECTIVES To establish the effectiveness of the Green Prescription physical activity counseling program in increasing activity and quality of life in older community-dwelling people . DESIGN Post hoc subgroup analysis of a large cluster r and omized , controlled trial . SETTING One hundred seventeen doctors in 42 primary care practice s ( 74 % participation rate ) in the Waikato region of New Zeal and . PARTICIPANTS Two hundred seventy sedentary primary healthcare patients aged 65 and older ( 67 % participation rate ) . INTERVENTION Patients in intervention practice s prompted their primary care doctors or practice nurse to deliver brief activity counseling . A " Green Prescription " was written involving the negotiation of activity goals . Trained exercise specialists from a regional sports foundation gave follow-up telephone support over 3 months . MEASUREMENTS Leisure moderate and vigorous physical activity , total energy expenditure , systolic and diastolic blood pressure , health-related quality of life , musculoskeletal injuries , falls , and hospitalizations . RESULTS After 12 months of follow-up , leisure time moderate activity increased by 0.67 h/wk more in the intervention group than the control group ( 95 % confidence interval (CI)=0.17 - 1.17 ) and energy expenditure increased by 2.67 kcal/kg per week ( 95 % CI=0.87 - 4.47 ) more . For intervention group participants , vitality and general health scales of the 36-item Short Form showed statistically and clinical ly relevant improvements , and there was a decrease in hospitalizations ( P<.03 ) . There were no observable changes in blood pressure , injuries , or falls as a result of the Green Prescription program . CONCLUSION This physical activity intervention improved activity , energy expenditure , health-related quality of life , and hospitalizations for older primary care patients . Systematic inclusion of the Green Prescription in routine primary health care will probably lead to health gain for older people OBJECTIVE To examine the contribution of social-cognitive factors ( self-efficacy and affect ) in predicting long-term physical activity in a sample of older adults ( N=174 ) . DESIGN A prospect i ve design assessed physical activity and psychosocial variables at 2 and 5 years following a 6-month r and omized , controlled exercise trial . MAIN OUTCOME MEASURES The primary outcome variable was self-reported physical activity , with previous behavior , self-efficacy , and affect assessed as determinants of physical activity . RESULTS Covariance modeling analyses indicated that physical activity at Year 2 was the strongest predictor of physical activity at 5-year follow-up . Both self-efficacy and affect at Year 2 were also associated with physical activity at Year 5 , as was original treatment condition . Variables accounted for 35 % of the variance in Year 5 activity . CONCLUSION Older adults with higher levels of physical activity , more positive affect , and higher self-efficacy at Year 2 were more likely to continue to be active at Year 5 . This study is one of the longest follow-ups of exercise behavior in older adults and has implication s for structuring environments to maximize the maintenance of physical activity Background : Data regarding the effect of exercise programmes on older adults ’ health-related quality of life ( HRQOL ) and habitual physical activity are inconsistent . Objective : To determine whether a functional tasks exercise programme ( enhances functional capacity ) and a resistance exercise programme ( increases muscle strength ) have a different effect on the HRQOL and physical activity of community-dwelling older women . Methods : Ninety-eight women were r and omised to a functional tasks exercise programme ( function group ) , a resistance exercise programme ( resistance group ) , or normal activity group ( control group ) . Participants attended exercise classes three times a week for 12 weeks . The SF-36 Health Survey question naire and self-reported physical activity were obtained at baseline , directly after completion of the intervention ( 3 months ) , and 6 months later ( 9 months ) . Results : At 3 months , no difference in mean change in HRQOL and physical activity scores was seen between the groups , except for an increased SF-36 physical functioning score for the resistance group compared with the control group ( p = 0.019 ) and the function group ( p = 0.046 ) . Between 3 and 9 months , the self-reported physical functioning score of the function group decreased to below baseline ( p = 0.026 ) , and physical activity ( p = 0.040 ) decreased in the resistance group compared with the function group . Conclusions : Exercise has a limited effect on the HRQOL and self-reported physical activity of community-living older women . Our results suggest that in these subjects HRQOL measures may be affected by ceiling effects and response shift . Studies should include performance-based measures in addition to self-report HRQOL measures , to obtain a better underst and ing of the effect of exercise interventions in older adults PURPOSE To investigate the effectiveness of a peer-mentored exercise program , this study compared the program perception , retention and participation rates , and physical improvements of older adults trained by peer mentors ( PMs ) with those of a group trained by student mentors ( SMs ) . METHODS After a 30-week peer-mentor preparation , 60 older adults ( M + /- SD age : 68.7 + /- 6.1 yr ) were recruited and r and omly assigned to either the PM or the SM group . Both groups completed an identical 14-week fitness program . Pre- and posttraining assessment s of fitness were completed , and the efficacy of the PMs and SMs was surveyed . RESULTS High retention was observed in both groups , but the SM group had higher participation . Both groups improved their fitness significantly , with no significant posttest differences between the groups in most fitness measures or in program perception rates . DISCUSSION Findings suggest effectiveness of the peer-mentor model in an older adult exercise program OBJECTIVE To assess the effectiveness of a primary care referral scheme on increasing physical activity at 1 year from referral . Design Two-group r and omized controlled trial recruiting primary care referrals to a borough-based exercise scheme . Setting A local authority borough in the north-west of Engl and . Participants 545 patients defined as sedentary by a primary care practitioner . Intervention Referral to a local-authority exercise referral scheme and written information compared with written information only . Main outcome measures Meeting physical activity target at 12 months following referral , with a secondary outcome measured at 6 months from referral . RESULTS At 12 months , a non-significant increase of 5 per cent was observed in the intervention compared with control group , for participation in at least 90 minutes of moderate/vigorous activity per week ( 25.8 versus 20.4 per cent , OR 1.45 , 0.84 to 2.50 , p = 0.18 ) . At 6 months , a 10 per cent treatment effect was observed which was significant ( 22.6 versus 13.6 per cent , OR 1.67 , 1.08 to 2.60 , p = 0.05 ) . The intervention increased satisfaction with information but this did not influence adherence with physical activity . CONCLUSION Community-based physical activity referral schemes have some impact on reducing sedentary behaviour in the short-term , but which is unlikely to be sustained and lead to benefits in terms of health OBJECTIVES To describe activity patterns associated with a pedometer intervention in university freshmen and compare the intervention participants to controls for several health outcomes . METHODS Forty-six university freshmen were r and omized to a group that wore a pedometer across the academic year with a goal of 10,000 steps/day or to a control group . RESULTS Pedometer counts were highest initially but decreased over the academic year . December presented the fewest counts . There was little difference between groups in fitness or body composition . CONCLUSIONS Consideration of high-risk months and recommended steps/day may be important to effectively use pedometers to influence some health outcomes in university freshmen ABSTRACT A 6-month home-based ( HB ) physical activity program was compared to a control ( CTL ) condition in terms of effect on physical activity and health-related fitness in three generations of women ( daughter/mother/maternal gr and mother ) . Volunteers were r and omly assigned to a HB or CTL condition . HB participants ( n = 28 ) were asked to participate in lifestyle , aerobic , muscular strength , and flexibility activities at least 3 times per week and they completed 73 % of the recommended PA bouts . CTL condition participants ( n = 9 ) were asked to continue their usual pattern of physical activity . Changes in physical activity were measured pre- and post-intervention using the Physical Best question naire and pedometer step counts ( 3-day average ) . Changes in health-related fitness were assessed using Fitnessgram tests . Group × Time interactions were significant for changes in participation in flexibility activity ( d/wk ) and steps/day , indicating that the HB group experienced significant positive changes in the expected direction ( + 305 % and + 37 % , respectively ) , while the CTL group regressed ( −15 % and −13 % , respectively ) . The G × T interaction for mile time was significant , although not in the expected direction ( CTL group < by 14 % and HB group < by 5 % ) . Findings should be interpreted with caution due to several limitations of the study , but several suggestions are made for more effectively study ing this topic in the future Background : Both urban and rural adults are likely to be inactive , but rural adults have less access to exercise classes or facilities to increase physical activity . Objectives : To evaluate whether a telephone-only motivational interviewing ( MI ) intervention would increase daily physical activity of rural adults . Methods : This r and omized controlled trial enrolled 86 physically inactive adults living in rural communities ( mean age = 58 years , range = 30 - 81 years ) who stated that they were ready to increase physical activity during the next 6 months . Participants were assigned r and omly to MI intervention ( n = 43 ) or control ( n = 43 ) groups . The MI group participants received a pedometer and monthly MI telephone calls over 6 months from a counselor . Control group participants received an equal number of telephone calls without MI content . Physical activity was measured by self-report using the Community Healthy Activities Model Program For Seniors Physical Activity Question naire for Older Adults . Data were collected by mailed surveys and analyzed using analysis of variance . Results : Seventy-two participants completed the study ( 35 in the intervention group and 37 in the control group ) . The telephone-only MI intervention increased self-efficacy for exercise ( p = .019 ) but did not increase levels of physical activity ( p = .572 ) compared with controls . Discussion : The intervention increased self-efficacy for exercise but did not increase physical activity , possibly due to seasonal effects , the control condition , or the length of the MI intervention . Even so , future studies are warranted because telephone-only MI has potential as a practical , relatively inexpensive method to provide health counseling to rural adults in a broad geographic area . This study produced an effect size on physical activity that will be useful to guide future studies OBJECTIVE To increase walking activity in sedentary women . METHODS Women ( N = 253 ) were r and omly assigned to 1 of 3 groups : video education/control , brief telephone calls with no counseling , and telephone calls with counseling . Assessment s were made at baseline , 6 months , and 1 year . RESULTS All interventions increased the number of reported minutes walked and decreased the time to walk a mile . CONCLUSIONS The variability in the telephone counseling and brief telephone call groups seemed to suggest a group of participants who were high responders Despite the importance of self-care for dementia caregivers , few interventions have included a focus on health behaviors . This study reports outcomes of a telephone-based exercise intervention design ed for women caring for a spouse with dementia . Caregivers ( N = 137 ) were r and omized to intervention or control conditions . Participants with at- or below-median exercise scores at baseline had a significantly greater increase in exercise at 6-month follow-up compared with their control counterparts . At 6 months , participants had greater reductions in perceived stress relative to controls . Participants also reported significantly greater increases in exercise self-efficacy than caregivers in the control group at both follow-up points . Results indicate that spouse caregivers are able to increase their physical activity and that a focus on exercise in multicomponent interventions may be beneficial . Debate and discussion are needed to inform expectations for program effects and their maintenance and to explore the interface between enhanced self-care and caregiving perceptions BACKGROUND Computerized , tailored interventions have the potential to be a cost-effective means to assist a wide variety of individuals with behavior change . This study examined the effect of computerized tailored physical activity reports on primary care patients ' physical activity at 6 months . DESIGN Two-group r and omized clinical trial with physicians as the unit of r and omization . Patients were placed in the intervention ( n=187 ) or control group ( n=207 ) based on their physician 's assignment . SETTING / PARTICIPANTS Primary care physicians ( n=22 ) and their adult patients ( n=394 ) from Philadelphia PA . The study and analyses were conducted from 2004 to 2010 . INTERVENTION The intervention group completed physical activity surveys at baseline , 1 , 3 , and 6 months . Based on their responses , participants received four feedback reports at each time point . The reports aim ed to motivate participants to increase physical activity , personalized to participants ' needs ; they also included an activity prescription . The control group received identical procedures , except that they received general reports on preventive screening based on their responses to preventive screening questions . MAIN OUTCOME MEASURES Minutes of physical activity measured by the 7-Day Physical Activity Recall interview at 6 months . RESULTS Participants were 69 % female , 59 % African-American , and had diverse educational and income levels ; the retention rate was 89.6 % . After adjusting for baseline levels of activity and gender , there were no differences in physical activity at 6 months . The intervention group increased their total physical activity by a mean of 139 minutes ; the control group had a mean increase of 109 minutes ( p=0.45 ) . CONCLUSIONS Although physical activity increased within both groups , computerized tailored physical activity reports did not significantly increase physical activity between groups at 6 months among ethnically and socioeconomically diverse adults in primary care OBJECTIVE --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy , sedentary older adults . DESIGN --Year-long r and omized , controlled trial comparing ( 1 ) higher-intensity group-based exercise training ; ( 2 ) higher-intensity home-based exercise training ; ( 3 ) lower-intensity home-based exercise training ; or ( 4 ) assessment -only control . SETTING --General community located in northern California . PARTICIPANTS --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease . One out of nine persons contacted through a community r and om-digit-dial telephone survey and citywide promotion were r and omized . INTERVENTIONS --For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise training , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . MAIN OUTCOME MEASURES --Treadmill exercise test performance , exercise participation rates , and heart disease risk factors . RESULTS --Compared with controls , subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months ( P less than .03 ) . Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training . Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition ( P less than .0005 ) . There were no significant training-induced changes in lipid levels , weight , or blood pressure . CONCLUSIONS --We conclude that ( 1 ) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary , healthy older adults ; ( 2 ) home-based exercise was as effective as group exercise in producing these changes ; ( 3 ) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting ; and ( 4 ) the exercise programs were relatively safe BACKGROUND Project STRIDE is a 4-year r and omized controlled trial comparing two computer-based expert system guided intervention delivery channels ( phone vs. print ) for physical activity adoption and short-term maintenance among previously sedentary adults . METHODS Sedentary adults ( n=239 ) were r and omized to one of the following ( 1 ) telephone-based , individualized motivationally-tailored feedback ; ( 2 ) print-based , individualized motivationally-tailored feedback ; ( 3 ) contact-control delayed treatment group ( received intervention after 12 months as control ) . This paper : ( 1 ) outlines the study design , rationale , and participant sample ; and ( 2 ) describes relationships between baseline variables to better underst and their influence on the efficacy of the intervention . RESULTS Participants averaged 19.8+/-25.0 min of physical activity/week that was at least of moderate intensity , with no group differences . The average estimated VO(2 ) at 85 % of maximum heart rate was 25.6 ml/kg/min . Body fat was 34.1 % for women and 23.2 % for men and the BMI of the sample averaged 28.5 kg/m(2 ) . CONCLUSIONS Project STRIDE examines non face-to-face approaches for promoting physical activity behavior . It has unique features including a direct comparison of an expert system guided intervention delivered via phone or print . Future analyses will examine the cost-effectiveness of the interventions and this will likely yield important information for policy-makers Over two-thirds of Americans access the Internet and therefore , the Internet may be an important channel for reaching the large population of sedentary individuals . The purpose of this paper is to describe the methods for a r and omized controlled trial examining the efficacy of an Internet-based physical activity intervention relative to a print intervention that has been shown to be effective in previous trials . Specifically , 249 sedentary participants were r and omized to receive one of three interventions : 1 ) Internet-based motivationally-tailored individualized feedback ( Tailored Internet ) ; 2 ) print-based motivationally-tailored individualized feedback ( Tailored Print ) ; or 3 ) physical activity websites currently available to the public ( St and ard Internet ) . Participants completed the 7-Day Physical Activity Recall interview , wore an objective physical activity monitor ( i.e. , ActiGraph ) , and participated in a treadmill fitness test at baseline , 6 , and 12 months . The sample consisted of mostly women ( 84.2 % ) and Caucasian individuals ( 76.4 % ) who reported exercising an average of 21 min per week at baseline . This is the first study that we are aware of , that has examined the efficacy of a tailored Internet-based physical activity intervention . This study will have implication s for the dissemination of Internet-based physical activity interventions The purpose of this study was to test the feasibility of the WALC intervention ( Walk ; Address pain , fear , fatigue during exercise ; Learn about exercise ; Cue by self-modeling ) , and determine its effects on self-efficacy and outcome expectations , exercise activity and free living activity , physical and mental health status , and falls and fall-related injuries . A total of 17 sedentary older women with a mean age of 88 + /- 3.7 years were r and omly assigned to receive either the WALC intervention or routine care . Ninety percent of those in the treatment group initiated and engaged in a regular exercise program during the 6 months of the study . There was a statistically significant difference in self-efficacy expectations , exercise behavior , and overall activity between the two groups . Those in the treatment group had stronger self-efficacy expectations related to exercise ; engaged in more exercise and more free living activity ; and although not statistically significant , had stronger outcome expectations following exposure to the WALC intervention when compared with those who received routine care . To help older adults initiate and adhere to an exercise program , nurses can easily implement the WALC intervention in a variety of setting OBJECTIVES This study examined the health-related effects of two worksite interventions , physical exercise and reduced workhours , on women employed in dentistry . METHODS Six workplaces were r and omized to one of the following three conditions : ( i ) 2.5 hours of weekly , m and atory physical exercise of middle-to-high intensity to be performed during workhours ( N=62 ) , ( ii ) a reduction of full-time weekly workhours from 40 to 37.5 hours ( N=50 ) , and ( iii ) reference . In all , 177 women participated . Biomarkers and self-ratings in question naires were obtained before the intervention ( T ( 1 ) ) , and six ( T ( 2 ) ) and 12 months ( T ( 3 ) ) after the intervention . RESULTS The results showed increased levels of physical activity and exercise in all of the groups , the level of physical exercise being significantly greater in the physical exercise group . Repeated- measures analyses of variance using data from T ( 1 ) and T (3)for biological measures and all three time points for self-ratings produced significant interaction effects for glucose , waist-to-hip ratio , and work ability and clear trends for general symptoms and upper-extremity disorders . Posthoc analyses showed that the results of the health-related measures differed between the interventions , decreased glucose and upper-extremity disorders in the exercise group , and increased high-density lipoprotein and waist-to-hip ratio among those working reduced hours . CONCLUSIONS These results show that the two interventions had small and varied effects on biomarkers and self-reports of different aspects of health among women . It is suggested that interventions involving a modest reduction in workhours seem to be more effective if these hours are used for physical exercise The effects of one year of exercise training on cardiorespiratory fitness , levels of daily leisure activity , and blood lipids ( cholesterol and high density lipoproteins ) were studied in a prospect i ve , r and omized clinical trial . Two hundred and twenty-four men aged 55 to 65 years volunteered for the study and were r and omly allocated to a control ( n = 111 ) or an activity ( n = 113 ) group with stratification on blue or white collar job classification . After the attrition due to loss to follow-up , 100 men remained in each of the control and activity groups . The exercising men met an average of 2.5 times per week over the year and their VO2 max or peak VO2 ( ml X kg-1 X min-1 ) increased significantly ( p = .001 , 11 % ) compared with controls . There were no significant changes in maximal heart rate ( 155 bpm ) and respiratory exchange ratio ( 1.1 ) , although ventilation ( 80 to 90 l X min-1 ) increased significantly in the trained group . In addition , the VO2 at a heart rate of 125 bpm increased significantly ( p less than .001 ) in the trained group ( 14.7 % ) over that observed in the control ( 1.9 % ) . There were no significant differences between the groups with respect to the remaining end-points To assess the effectiveness of physician prescribed exercise , health education , and patient self-monitoring , 124 firefighters were medically screened and r and omly allocated to a control and two treatment groups . Physiologic and reporting methods were employed to assess adherence to regular exercise at three months and six months after the initial exercise prescription . Addition of a health education program significantly improved compliance over that achieved by a physician consultation . Self-monitoring did not produce a further increase in compliance . Improvement in the treatment groups was limited to three months after prescription ; at six months , the treatment and control population s had similar exercise patterns BACKGROUND Regular physical activity reduces the risk for chronic diseases among older adults . Older adults are likely to be seen by primary care clinicians who can play a role in promoting physical activity among their patients . DESIGN In this r and omized controlled trial ( 1998 - 2003 ; data analyzed 2004 - 2005 ) , we compared the effects of brief advice to exercise from a clinician supplemented by telephone-based counseling by health educators ( extended advice ) to brief advice from a clinician alone ( brief advice ) . SETTING / PARTICIPANTS A total of 100 primary care patients ( 63.2 % female , 14.7 % minority , mean age=68.5 years ) participated in the trial . INTERVENTIONS The extended-advice intervention consisted of clinician advice plus exercise counseling via telephone provided by research staff , and the brief advice condition consisted of clinician advice alone . Both interventions focused on promoting moderate-intensity physical activity . MAIN OUTCOME MEASURES Self-reported physical activity using the 7-Day Physical Activity Recall instrument and objective activity monitoring using Biotrainers were assessed at baseline , and at 3 and 6 months . RESULTS Participants in the extended-advice arm reported significantly greater participation in moderate-intensity physical activity than the brief-advice group at 3 months ( + 57.69 minutes vs 12.45 minutes ; 3.84 kcal/week vs 0.83 kcal/week ) and 6 months ( + 62.84 minutes vs 16.60 minutes ; 4.19 kcal/week vs 1.1 kcal/week ) . Objective activity monitoring also showed significantly increased physical activity among extended-advice versus brief-advice participants at both time points ( + 50.79 vs -11.11 ; + 42.39 vs -24.18 , respectively ) . CONCLUSIONS These data indicate that clinician advice with follow-up counseling can promote adoption of moderate-intensity physical activity among older , primary care patients To investigate the applicability and effectiveness of a peer-mentored exercise program , this study compared the retention and participation rates , and physical improvements of older adults trained by peer mentors ( PM ) to a group trained by young qualified student mentors ( SM ) . A group of older adults were prepared as peer mentors through a 30-week preparation program . Later , 60 older adults ( mean ± SD age : 68.7 ± 6.1 years ) were recruited and r and omly assigned to either the PM or SM group . Both groups completed an identical 35-week fitness program . Pre- , midterm- and post-training assessment s of fitness were completed and rates of participation and retention were documented . The same retention rates were observed in the two groups , but SM group had higher participation . Both groups improved significantly in all measures of fitness and there were no significant post-test differences between the groups in the fitness measures . Findings suggest that the peer mentor model is applicable in an older adult exercise program and may be as effective as a program mentored by young professionals Sixty-four male and female sedentary employees were r and omly assigned to an intervention group or control group to determine the effects of behavioral skill training on adoption and maintenance of exercise . Both received a 9-month membership at a local fitness facility . The control group received a 12-week semistructured course , which included a facility orientation and three meetings with a personal trainer . The intervention group received a 12-week behavioral skills course and were encouraged to participate in a 12-week semistructured exercise course followed by a 3-month problem-solving support intervention . Both groups improved their daily energy expenditure , the amount of moderate and vigorous activity they performed , and their strength and flexibility . The study sample was too small to show substantial differences between the intervention and control group . Changes in mediator variables were mixed Purpose . To compare the effects of stage-matched and st and ard print material s for physical activity ( PA ) change . Design . Participants were r and omized into ( 1 ) a stage-matched intervention group ( n = 165 ) , ( 2 ) a st and ard intervention group ( n = 176 ) , or ( 3 ) a no-contact control group ( n = 166 ) . The stage-matched and st and ard intervention groups both received material s at baseline , 3 months , and 6 months . Assessment s of all three groups were conducted at baseline , 6 , and 12 months . Setting . Canadian worksites . Subjects . Employees ( N = 507 ) . Interventions . Five motivationally targeted booklets were developed for the stage-matched group . The st and ard group received Canada 's Physical Activity Guide and h and book . Measures . The main dependent variable was PA , expressed as metabolic equivalent ( MET ) minutes and measured using the Godin Leisure-Time Exercise Question naire . Demographic characteristics and stages of change for PA were also assessed . Results . At 12 months mean weekly MET minutes for combined moderate and vigorous activity increased from baseline by 223 , 67 , and 78 for the stage-matched , st and ard , and control groups , respectively ; however , differences were not significant ( p > .05 ) . Women in the stage-matched group over the 12-month period significantly increased their activity by 327 weekly MET minutes whereas the st and ard and control groups declined their activity ( F = 3.01 , p < .05 ) . Conclusion . PA stage-matched material s delivered in the workplace are efficacious for women but not men . Future interventions should explore the use of these intervention material s in conjunction with multilevel strategies , and particular attention should be paid to possible gender differences |
2,121 | 30,157,250 | Retrospective comparisons of recruitment methods showed that non-web-based advertisement and recruitment by clinical research staff each have advantages in efficiency .
Financial incentives , abridged question naires and pre-notification had a positive effect on retention rates .
The recruitment studies included showed differences in strategies , clinical setting s , mental health conditions and study design .
It is difficult to assess the overall effectiveness of any particular recruitment strategy as some strategies that worked well for a particular population may not work as well for others .
Paying attention to the accessibility of information and consent material s may help improve recruitment . | BACKGROUND Recruitment and retention challenges are very common in mental health r and omised trials .
Investigators utilise different methods to improve recruitment or retention .
However , evidence of the effectiveness and efficiency of these strategies in mental health has not been synthesis ed .
This systematic review is to investigate and assess the effectiveness and cost-effectiveness of different strategies to improve recruitment and retention in mental health r and omised trials . | Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity Background Recruiting participants to r and omized controlled trials of health interventions can be very difficult . Internet-based recruitment is becoming an increasingly important mode of recruitment , yet there are few detailed accounts of experiences recruiting participants to mental health interventions . Objective To report on our experience with Internet-based recruitment to an online depression prevention intervention and pass on lessons we learned . Methods Participants were recruited to the Mood Memos study , an online preventive depression intervention , purely through Internet-based sources . The study was targeted to adults with subthreshold depression symptoms from several English-speaking countries . A variety of online recruitment sources were trialed , including search engine advertising ( Google , Yahoo ! , Bing ) , Facebook advertising , posts in forums and online noticeboards , and promotion through relevant websites and email newsletters of mental health organizations . Results The study website received visits from 94,808 individuals over the 14-month recruitment period . The recruitment target was reached with 1699 individuals signing up to the r and omized controlled trial and 1326 fully enrolling . Most visitors arrived via Google advertising , which promoted a depression-screening question naire . Google advertising accounted for nearly half of the total participants who signed up to the study , at an average cost of AUD $ 12 per participant . Promoting the study through trustworthy organizations and websites known to participants was also effective . Recruitment techniques that were less effective were contacting forums , email groups , and community noticeboards . Conclusions Several techniques , including Google advertising , were successful in recruiting participants to a trial evaluating an online depression intervention . Results suggest that Internet-based recruitment to mental health interventions is feasible and can be relatively affordable . Trial Registration Background Under-recruitment to r and omised controlled trials ( RCTs ) is often problematic and there may be particular difficulties in recruiting patients with severe mental illness . Aim To evaluate reasons for under-recruitment in an RCT of patients with severe mental illness Methods Qualitative study during the recruitment phase of an RCT of supported employment . Trial staff and recruiting clinicians were interviewed . Data were analyzed thematically using constant comparative techniques . Results Recruitment rates were low . Five main reasons for recruitment difficulties were found . These included : ( i ) misconceptions about trials , ( ii ) lack of equipoise , ( iii ) misunderst and ing of the trial arms , ( iv ) variable interpretations of eligibility criteria , ( v ) paternalism . Conclusion Reasons for recruitment difficulties in trials involving patients with severe mental illness include issues that occur in trials in general , but others are more specific to these patients . Clinician and patient involvement in the study design may improve recruitment in future similar trials Background Patient and public involvement in research ( PPIR ) may improve trial recruitment rates , but it is unclear how . Where trials use PPIR to improve design and conduct , many do not communicate this clearly to potential participants . Better communication of PPIR might encourage patient enrolment , as trials may be perceived as more socially valid , relevant and trustworthy . We aim ed to evaluate the impact on recruitment of directly advertising PPIR to potential trial participants . Methods This is a cluster trial , embedded within a host trial ( ‘ EQUIP ’ ) recruiting service users diagnosed with severe mental illness . The intervention was informed by a systematic review , a qualitative study , social comparison theory and a stakeholder workshop including service users and carers . Adopting Participatory Design approaches , we co- design ed the recruitment intervention with PPIR partners using a leaflet to advertise the PPIR in EQUIP and sent potential participants invitations with the leaflet ( intervention group ) or not ( control group ) . Primary outcome was the proportion of patients enrolled in EQUIP . Secondary outcomes included the proportions of patients who positively responded to the trial invitation . Results Thirty-four community mental health teams were r and omised and 8182 service users invited . For the primary outcome , 4 % of patients in the PPIR group were enrolled versus 5.3 % of the control group . The intervention was not effective for improving recruitment rates ( adjusted OR = 0.75 , 95 % CI = 0.53 to 1.07 , p = 0.113 ) . For the secondary outcome of positive response , the intervention was not effective , with 7.3 % of potential participants in the intervention group responding positively versus 7.9 % of the control group ( adjusted OR = 0.74 , 95 % CI = 0.53 to 1.04 , p = 0.082 ) . We did not find a positive impact of directly advertising PPIR on any other outcomes . Conclusion To our knowledge , this is the largest ever embedded trial to evaluate a recruitment or PPIR intervention . Advertising PPIR did not improve enrolment rates or any other outcome . It is possible that rather than advertising PPIR being the means to improve recruitment , PPIR may have an alternative impact on trials by making them more attractive , acceptable and patient-centred . We discuss potential reasons for our findings and implication s for recruitment practice and research .Trial registration numbersIS RCT N , IS RCT N16488358 . Registered on 14 May 2014 . Study Within A Trial , SWAT-26 . Registered on 21 January 2016 Background Patient underst and ing of study information is fundamental to gaining informed consent to take part in a r and omised controlled trial . In order to meet the requirements of research ethics committees , patient information material s can be long and need to communicate complex messages . There is concern that st and ard approaches to providing patient information may deter potential participants from taking part in trials . The Systematic Techniques for Assisting Recruitment to Trials ( MRC-START ) research programme aims to test interventions to improve trial recruitment . The aim of this study was to investigate the effect on recruitment of optimised patient information material s ( with improved readability and ease of comprehension ) compared with st and ard material s. The study was embedded within two primary care trials involving patients with long-term conditions . Methods The Healthlines Study involves two linked trials evaluating a telehealth intervention in patients with depression ( Healthlines Depression ) or raised cardiovascular disease risk ( Healthlines CVD ) . We conducted two trials of a recruitment intervention , embedded within the Healthlines host trials . Patients identified as potentially eligible in each of the Healthlines trials were r and omised to receive either the original patient information material s or optimised versions of these material s. Primary outcomes were the proportion of participants r and omised ( Healthlines Depression ) and the proportion expressing interest in taking part ( Healthlines CVD ) . Results In Healthlines Depression ( n = 1364 ) , 6.3 % of patients receiving the optimised patient information material s were r and omised into the study compared to 4.0 % in those receiving st and ard material s ( OR = 1.63 , 95 % CI = 1.00 to 2.67 ) . In Healthlines CVD ( n = 671 ) 24.0 % of those receiving optimised patient information material s responded positively to the invitation to participate , compared to 21.9 % in those receiving st and ard material s ( OR = 1.12 , 95 % CI = 0.78 to 1.61 ) . Conclusions Evidence from these two embedded trials suggests limited benefits of optimised patient information material s on recruitment rates , which may only be apparent in some patient population s , with no effects on other outcomes . Further embedded trials are needed to provide a more precise estimate of effect , and to explore further how effects vary by trial context , intervention , and patient population .Trial registration Current Controlled Trials : Healthlines Depression ( IS RCT N27508731 ) on 26 June 2012 ; and Healthlines CVD ( IS RCT N14172341 ) on 5 July Background Mindfulness interventions to reduce psychological distress are well-suited to pregnancy , due to their brief and non-pharmacological nature , but there is a need for more robust evidence determining their usefulness . This pilot study was design ed to explore the feasibility of a r and omised controlled trial of a mindfulness intervention to reduce antenatal depression , anxiety and stress . Methods The study was design ed in two parts 1 ) a non-r and omised trial targeting women at risk of mental health problems ( a selected population ) and 2 ) a r and omised controlled trial ( RCT ) of a universal population . Process evaluation focused on feasibility of recruitment pathways , participant retention , acceptability of study measures , and engagement with mindfulness practice s. Measurement of psychological distress was taken pre and post intervention through the Centre for Epidemiologic Studies Depression Scale Revised , the Depression Anxiety and Stress Scale-21 , the State-Trait Anxiety Inventory , and the Perceived Stress Scale . Results 20 women were recruited to the non-r and omised trial , and 32 to the RCT . Recruitment through a mailed study brochure at the time of booking-in to the hospital result ed in the largest number of participants in the RCT ( 16/32 ; 50 % ) , and result ed in considerably earlier recruitment ( 50 % in first trimester , 50 % second trimester ) compared to recruitment through the antenatal clinic waiting room ( 86 % in second trimester , 14 % third trimester ) . Over a third of women in the universal population scored above clinical cut-offs for depression and anxiety , indicating a sample with more symptomology than the general population . The most common reason for loss to follow-up was delivery of baby prior to follow-up ( n = 9 ) . In the non-r and omised study , significant within group improvements to depression and anxiety were observed . In the intervention arm of the RCT there were significant within group improvements to anxiety and mindfulness . No between group differences for the intervention and ` care as usual ’ control group were observed . Conclusions This small pilot study provides evidence on the feasibility of an antenatal mindfulness intervention to reduce psychological distress . Major challenges include : finding ways to facilitate recruitment in early pregnancy and engaging younger women and other vulnerable population s . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12613000742774 ( 31/10/2012 ) OBJECTIVE Our aim was to analyze monetary incentives and shortening the question naire as means of increasing response rates in a mailed follow-up survey 1 year after inpatient psychotherapeutic treatment . Additionally , effects on partial nonresponse and the assessment of treatment outcome were examined . STUDY DESIGN AND SETTING In a 2x2 factorial design , a sample of 3,825 patients was r and omized to the two following interventions : ( 1 ) receiving a prepaid monetary incentive or none ; and ( 2 ) getting a short or a long question naire . Treatment outcome was measured prospect ively by a self- assessment instrument for psychopathology . RESULTS When using incentives , the response rate significantly increased by 7.3 % ( 95 % confidence interval [ CI ] 2.6 - 11.9 % ) . Receiving a short question naire led to an augmentation of the response rate of 3.7 % ( 95 % CI 0.9 - 8.3 % ) , which was not significant . The corresponding odds ratios were significantly increased for monetary incentives ( 1.36 ; 95 % CI 1.30 - 1.88 ) , and when abridging the question naire ( 1.15 ; 95 % CI 1.01 - 1.31 ) . However , partial nonresponse and treatment outcome were independent of the two factors . CONCLUSION Incentives and a shorter question naire led to higher return rates but did not affect partial nonresponse and self-report of treatment outcome in a r and omized postal survey Limitations of printed , text-based , consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity , such as those with schizophrenia . We conducted a r and omized controlled comparison of the effectiveness of a multimedia vs routine consent procedure ( augmented with a 10-minute control video presentation ) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects . The primary outcome measure was manifest decisional capacity ( underst and ing , appreciation , reasoning , and expression of choice ) for participation in a ( hypothetical ) clinical drug trial , as measured with the MacArthur Competence Assessment Tool for Clinical Research ( MacCAT-CR ) and the University of California San Diego ( UCSD ) Brief Assessment for Capacity to Consent ( UBACC ) . The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition . Additional assessment s included st and ardized measures of psychopathology and cognitive functioning . Relative to patients in the routine consent condition , schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR underst and ing and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition ( as categorized with several previously established criteria ) . Among the healthy subjects , there were few significant effects of consent condition . These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity , particularly for complex and /or high-risk research protocol BACKGROUND Postnatal depression is a serious mental health problem that may be reduced by exercise . AIM This study examined the feasibility of an exercise intervention for women with postnatal depression , and assessed which methods of recruitment are most effective . DESIGN OF STUDY R and omised controlled trial . SETTING General practice and the community . METHOD Participants were recruited from various sources and r and omised to an exercise intervention or usual care with follow-up at 12 weeks . As well as assessing feasibility , other trial outcomes included exercise participation and self-efficacy for exercise . Levels of depression were assessed but the study was not powered to show a difference in this . RESULTS The recruitment rate of eligible patients was 23.1 % . The highest recruitment rate was via referral from the psychiatric mother and baby unit ( 9/28 ; 32.1 % ) , followed by invitation letters from GPs ( 24/93 ; 25.8 % ) . Thirty-eight eligible participants were r and omised . At follow-up there was no significant difference in exercise participation between groups . The intervention group reported significantly higher self-efficacy for exercise compared to usual care , but depression scores did not differ . CONCLUSION Exercise participation over the 12-week period was not significantly increased , possibly because it is difficult to motivate women with postnatal depression to exercise , or the intervention was not sufficiently intensive . Eligible patients were recruited into this study but response rates were low . Optimum methods of recruitment in this difficult-to-reach population are required prior to a substantive trial . Further research is imperative given poorly- evidence d recommendations by the National Institute for Health and Clinical Excellence to consider this treatment The negative consequences of untreated depression on the health and well-being of women and their children are well-documented , underscoring the need to develop effective interventions to prevent the onset of major depression during the perinatal period . This article describes recruitment data from two r and omized controlled trials of preventive interventions for postpartum depression : one conducted with immigrant Latinas in Washington , DC , United States , and the other with women in Mexico City , Mexico . In both countries , pregnant women met a priori eligibility criteria and were r and omized into an 8-week theory-based group intervention . Two hundred and seventeen Latinas in the U.S. and 377 women born and raised in Mexico were enrolled in their respective countries . The recruitment rates ( i.e. , the number of participants who met eligibility criteria , consented , and r and omized into the study ) were 70 % in the U.S. and in Mexico . Issues and recommendations related to recruiting Hispanic women into preventive intervention trials for postpartum depression are discussed OBJECTIVE To investigate the perceived barriers among GPs towards introducing participation in r and omized controlled trials ( RCTs ) to patients presenting with depression during consultations . METHODS Qualitative study using semi-structured interviews . Interviews were recorded using a digital voice recorder , transcribed verbatim and analysed using the Framework Approach . The participants were 41 GPs from five primary care trusts in the South West who were collaborating with the University of Bristol on an RCT recruiting patients with depression . RESULTS Three themes were identified : ( i ) concern about protecting the vulnerable patient and the impact on the doctor-patient relationship ; ( ii ) the perceived lack of skill and confidence of GPs to introduce a request for research participation within a potentially sensitive consultation ; and ( iii ) the priority given to clinical and administrative issues over research participation . These themes were underpinned by GPs ' observations that consultations with people about depression differed in content , style and perceived difficulty compared to other types of consultations . CONCLUSION Depressed patients were often viewed as vulnerable and in need of protection and it was seen as difficult and intrusive to introduce research . Patients were not always given the choice to participate in research in the same way that they are encouraged to participate in treatment decision making . A lack of skills in introducing research could be addressed with training through the new Primary Care Research Network . A more radical change in clinician attitudes and policy may be needed in order to give research a higher priority within primary care OBJECTIVE To explore effects of various recruitment strategies on r and omized clinical trial ( RCT ) -entry characteristics for patients with eating disorders within an everyday health-plan practice setting . METHODS R and omly selected women , aged 25 - 50 , in a Pacific Northwest HMO were invited to complete a self-report binge-eating screener for two treatment trials . We publicized the trials within the health plan to allow self-referral . Here , we report differences on eating-disorder status by mode and nature of recruitment ( online , mail , self-referred ) and assessment ( comprehensive versus abbreviated ) and on possible differences in enrollee characteristics between those recruited by strategy ( self-referred versus study -outreach efforts ) . RESULTS Few differences emerged among those recruited through outreach who responded by different modalities ( internet versus mail ) , early-versus-late responders , and those enrolling under more comprehensive or abbreviated assessment . Self-referred were more likely to meet binge-eating thresholds and reported higher average BMI than those recruited by outreach and responding by mail ; however , in most respects the groups were more similar than anticipated . Fewer than 1 % of those initially contacted through outreach enrolled . CONCLUSIONS Aggressive outreach and screening is likely not feasible for broader dissemination in everyday practice setting s and recruits individuals with more similar demographic and clinical characteristics to those recruited through more abbreviated and realistic screening procedures than anticipated Background R and omized controlled trials ( RCTs ) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies . However , research ers conducting RCTs commonly report difficulties in recruiting an adequate sample within planned timescales . In an effort to overcome recruitment difficulties , research ers often are forced to exp and their recruitment criteria or extend the recruitment phase , thus increasing costs and delaying publication of results . Research investigating the effectiveness of recruitment strategies is limited , and trials often fail to report sufficient details about the recruitment sources and re sources utilized . Purpose We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression . Methods We describe eight recruitment methods utilized and two further sources not initiated by the research team and examine their efficacy in terms of ( 1 ) the return , including the number of potential participants who contacted the trial and the number who were r and omized into the trial ; ( 2 ) cost-effectiveness , comprising direct financial cost and manpower for initial contacts and r and omized participants ; and ( 3 ) comparison of sociodemographic characteristics of individuals recruited from different sources . Results Poster advertising , web-based advertising , and mental health worker referrals were the cheapest methods per r and omized participant ; however , the ratio of r and omized participants to initial contacts differed markedly per source . Advertising online , via posters , and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were r and omized into the trial . Advertising across many sources ( saturation ) was found to be important . Limitations It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other population s , such as those currently unwell , or in other geographical locations . Recruitment source was unavailable for participants who could not be reached after the initial contact . Thus , it is possible that the efficiency of certain methods of recruitment was poorer than estimated . Efficacy and costs of other recruitment initiatives , such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to c and i date s who contacted the recruitment team but could not be screened promptly , were not analysed . Conclusion Website advertising result ed in the highest number of r and omized participants and was the second cheapest method of recruiting . Future research should evaluate the effectiveness of recruitment strategies for other sample s to contribute to a comprehensive base of knowledge for future RCTs The authors compared various strategies for recruiting elderly subjects with bereavement-related depression into a r and omized clinical trial . Over 5 years , they empaneled 65 patients from a total of 441 subjects screened ( 14.7 % ) . Response to media advertisements was the single most effective strategy ( 54 % of subjects ) . Another effective , but labor-intensive , strategy was using letters to bereaved spouses found through newspaper obituaries ( 14 % ) ; another 14 % were referred by friends who had seen study advertisements . Information letters to healthcare providers yielded no study participants . Pathways to study participation did not differ as a function of race or gender and did not influence study retention or remission rates . Our experience suggests that successful intake depends on a personal mode of recruitment OBJECTIVES Underst and ing attitudes to mental health issues can inform public health interventions . However , low response rates may contribute to nonresponse bias . In a r and omized controlled trial we examined the effect of sending a prenotification postcard before the question naire and the placement of a short message on the survey envelope ( teaser ) on response rates to a mailed question naire about bulimia nervosa " mental health literacy " . STUDY DESIGN AND SETTING Question naires were mailed to 3,010 adults ( 50.6 % female and 49.4 % male ) aged 18 - 65 years . In a 2 ( pre-notification-present ; absent ) by 2 ( teaser-present ; absent ) design , question naire recipients were r and omly allocated to the experimental strategies . Outcomes considered were response rate , response time , and cost . RESULTS The overall response rate was 22.0 % . Significant main effects showed higher response rates for the use of prenotification ( present = 23.6 % ; absent = 20.3 % ) , among female participants , and older participants . A significant interaction of teaser by gender indicated lower response rates for men who received the teaser but not for women . Older participants returned the question naire more promptly than younger participants . Females-but not males-who received the teaser were slower to return the question naire . Higher response rates for participants receiving the postcard compensated for increased costs , particularly for males and older participants . CONCLUSION Response rates to a mental health postal survey can be increased through the use of prenotification |
2,122 | 26,938,118 | An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure , and it seems to reduce the risk of sub clinical cardiac damage . | BACKGROUND This review up date has been managed by both the Childhood Cancer and Cochrane Gynaecological , Neuro-oncology and Orphan Cancer Groups .
The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity .
To prevent this cardiotoxicity , different anthracycline dosage schedules have been studied .
OBJECTIVES To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules ( that is peak doses and infusion duration s ) in people with cancer . | BACKGROUND A r and omized phase III trial in high-risk breast cancer patients was conducted , to further explore the impact of dose-density in the adjuvant treatment for breast cancer . The safety analysis is presented . PATIENTS AND METHODS From October 2000 until June 2005 , 1121 node-positive patients were r and omized to sequential dose-dense epirubicin 110 mg/m(2 ) and paclitaxel ( Taxol , Bristol Myers-Squibb , Princeton , New Jersey , USA ) 250 mg/m(2 ) ( group A ) , or concurrent epirubicin 83 mg/m(2 ) and paclitaxel 187 mg/m(2 ) ( group B ) , both followed by three cycles of ' intensified ' combination chemotherapy with cyclophosphamide , methotrexate and fluorouracil ( CMF ) . Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments . RESULTS Median dose intensity of epirubicin and paclitaxel was double in group A , as design ed , with significantly less cycles administered at full dose ( P < 0.001 ) . Median cumulative dose of all drugs and total treatment duration , however , were identical between groups . Severe taxane-related toxic effects were more frequent in group A , while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects , including febrile neutropenia . The rates of secondary malignancies were low . CONCLUSION Both regimens as used in the present study are well tolerated and safe . The rates of severe taxane-related toxic effects and thrombocytopenia , although low overall , are significantly increased with the dose-dense sequential regimen PURPOSE This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer BACKGROUND AND OBJECTIVES : Doxorubicin , effective against many malignancies , is limited by cardiotoxicity . Continuous-infusion doxorubicin , compared with bolus-infusion , reduces early cardiotoxicity in adults . Its effectiveness in reducing late cardiotoxicity in children remains uncertain . We determined continuous-infusion doxorubicin cardioprotective efficacy in long-term survivors of childhood acute lymphoblastic leukemia ( ALL ) . METHODS : The Dana-Farber Cancer Institute ALL Consortium Protocol 91 - 01 enrolled pediatric patients between 1991 and 1995 . Newly diagnosed high-risk patients were r and omly assigned to receive a total of 360 mg/m2 of doxorubicin in 30 mg/m2 doses every 3 weeks , by either continuous ( over 48 hours ) or bolus-infusion ( within 15 minutes ) . Echocardiograms at baseline , during , and after doxorubicin therapy were blindly remeasured central ly . Primary outcomes were late left ventricular ( LV ) structure and function . RESULTS : A total of 102 children were r and omized to each treatment group . We analyzed 484 serial echocardiograms from 92 patients ( n = 49 continuous ; n = 43 bolus ) with ≥1 echocardiogram ≥3 years after assignment . Both groups had similar demographics and normal baseline LV characteristics . Cardiac follow-up after r and omization ( median , 8 years ) showed changes from baseline within the r and omized groups ( depressed systolic function , systolic dilation , reduced wall thickness , and reduced mass ) at 3 , 6 , and 8 years ; there were no statistically significant differences between r and omized groups . Ten-year ALL event-free survival rates did not differ between the 2 groups ( continuous-infusion , 83 % versus bolus-infusion , 78 % ; P = .24 ) . CONCLUSIONS : In survivors of childhood high-risk ALL , continuous-infusion doxorubicin , compared with bolus-infusion , provided no long-term cardioprotection or improvement in ALL event-free survival , hence provided no benefit over bolus-infusion A phase II study utilizing VP-16 and adriamycin in a r and omized fashion tested the concept of synchronization of the drugs in treatment of metastatic breast cancer . Although there was a trend in median survival following the synchronized schedule , there was no significant difference in survival or progression-free intervals . The concept of synchronization was not established The Dana-Farber Cancer Institute ( DFCI ) acute lymphoblastic leukemia ( ALL ) Consortium Protocol 91 - 01 was design ed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity . Compared with prior protocol s , post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks . Between 1991 and 1995 , 377 patients ( age , 0 - 18 years ) were enrolled ; 137 patients were considered st and ard risk ( SR ) , and 240 patients were high risk ( HR ) . Following a 5.0-year median follow-up , the estimated 5-year event-free survival ( EFS ) + /- SE for all patients was 83 % + /- 2 % , which is superior to prior DFCI ALL Consortium protocol s conducted between 1981 and 1991 ( P = .03 ) . There was no significant difference in 5-year EFS based upon risk group ( 87 % + /- 3 % for SR and 81 % + /- 3 % for HR , P = .24 ) . Age at diagnosis was a statistically significant prognostic factor ( P = .03 ) , with inferior outcomes observed in infants and children 9 years or older . Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase ( P < .01 , both univariate and multivariate ) . Older children ( at least 9 years of age ) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase ( P < .01 ) . Treatment on Protocol 91 - 01 significantly improved the outcome of children with ALL , perhaps due to the prolonged asparaginase intensification and /or the use of dexamethasone . The inferior outcome of older children may be due , in part , to increased intolerance of intensive therapy A prospect i ve r and omized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin ( 60 mg/m2 every 3 to 4 weeks ) administered by bolus or 72‐hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high‐ grade soft tissue sarcoma of the extremity or superficial trunk . Cardiac toxicity , defined as a 10 % or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography , was evaluated in 69 patients . Cardiotoxicity was seen in 61 % of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2 . Among patients who received continuous infusion , 42 % had cardiotoxicity with a median dose of 540 mg/m2 . The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm ( P = 0.0017 ) . Two patients in each group had clinical congestive heart failure , with one cardiac death occurring in each . There was a trend toward a lower rate of metastasis ( P = 0.19 ) and a significantly lower rate of death of disease ( P = 0.036 ) for patients treated with the bolus dose . Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis : blood transfusion within 24 hours of operation ( P < 0.00001 ) , tumor deep to the fascia and 5 cm or more in size ( P = 0.0043 ) , and a histologic subtype other than liposarcoma ( P = 0.0002 ) . The unfavorable effect of continuous infusion was not selected in the model ( P = 0.16 ) . Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational . Furthermore , the impact of perioperative blood transfusion merits further study PURPOSE Patients with primary breast cancer who have extensive axillary lymph node involvement have a poor prognosis after conventional adjuvant therapy . We compared intense dose-dense ( IDD ) adjuvant chemotherapy with conventionally scheduled adjuvant chemotherapy in patients with high-risk primary breast cancer . PATIENTS AND METHODS In this r and omized , phase III trial , a total of 1,284 eligible patients with four or more involved axillary lymph nodes were r and omly assigned to receive IDD sequential epirubicin , paclitaxel , and cyclophosphamide ( IDD-ETC ) every 2 weeks or conventionally scheduled epirubicin/cyclophosphamide followed by paclitaxel every three weeks . The primary end point was event-free survival ( EFS ) . RESULTS At a median follow-up of 62 months , 5-year event-free survival rates were 62 % in the conventional arm and 70 % in the IDD-ETC arm , representing a 28 % reduction of the relative risk of relapse ( P < .001 ) . This benefit was independent of menopausal , hormone receptor , or human epidermal growth factor receptor 2 status . The 5-year overall survival rates were 77 % versus 82 % , representing a 24 % reduction of the relative risk of death ( P = .0285 ) . IDD therapy was associated with significantly more nonhematologic and hematologic toxicities , but no treatment-related death occurred . Four occurrences of acute myeloid leukemia or myelodysplastic syndrome ( MDS ) were observed in the IDD-ETC arm . No severe congestive heart failure was reported . CONCLUSION IDD-ETC was less well tolerated compared with conventional chemotherapy but significantly improved event-free and overall survivals in patients with high-risk primary breast cancer who had four or more positive axillary lymph nodes Forty-eight patients with advanced breast carcinoma who had not received prior chemotherapy ( minimum follow up 21 months ) were r and omised to receive either adriamycin 70 mg m-2 i.v . 3-weekly for 8 cycles ( Regimen A ) or adriamycin 35 mg m-2 i.v . 3-weekly for 16 courses ( Regimen B ) . Objective responses were seen in 14/24 ( 58 % ) patients with regimen A ( 4 complete ) and 6/24 ( 25 % ) with regimen B ( 1 complete ) ( P less than 0.02 ) . The median duration of response was 14 months with regimen A and 6.5 months with regimen B. The median duration of survival was 20 months and 8 months respectively ( P less than 0.01 ) . The toxicity was similar with each regimen . There was no evidence of deterioration in left ventricular ejection fraction nor congestive heart failure in any patient . It is concluded that when given at 3-weekly intervals adriamycin is a more effective treatment for advanced breast cancer at higher rather than lower dosage The activity and toxicity of single-agent st and ard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin . A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received ( A ) doxorubicin 75 mg m(-2 ) on day 1 ( 112 patients ) , ( B ) epirubicin 150 mg m(-2 ) on day 1 ( 111 patients ) or ( C ) epirubicin 50 mg m(-2 ) day(-1 ) on days 1 , 2 and 3 ( 111 patients ) ; all given as bolus injection at 3-week intervals . A median of four treatment cycles was given . Median age was 52 years ( 19 - 70 years ) and performance score 1 ( 0 - 2 ) . Of 314 evaluable patients , 45 ( 14 % ) had an objective tumour response ( eight complete response , 35 partial response ) . There were no differences among the three groups . Median time to progression for groups A , B and C was 16 , 14 and 12 weeks , and median survival 45 , 47 and 45 weeks respectively . Neither progression-free ( P = 0.93 ) nor overall survival ( P = 0.89 ) differed among the three groups . After the first cycle of therapy , two patients died of infection and one owing to cardiovascular disease , all on epirubicin . Both dose schedules of epirubicin were more myelotoxic than doxorubicin . Cardiotoxicity ( > or = grade 3 ) occurred in 1 % , 0 % and 2 % respectively . Regardless of the schedule , high-dose epirubicin is not a preferred alternative to st and ard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas PURPOSE Several multicomponent regimens have been reported to be useful in advanced and rogen-independent prostate cancer . We used a r and omized phase II design to evaluate and compare two such regimens . Patients were accrued primarily in the community setting . PATIENTS AND METHODS Patients with progressive , and rogen-independent prostate cancer were r and omly assigned to one of two treatments : either ketoconazole/doxorubicin alternating with vinblastine/estramustine ( KA/VE ) or paclitaxel , estramustine , and oral etoposide ( TEE ) . Patients were prospect ively stratified on the basis of disease volume . The primary end points were response and overall survival time . RESULTS A total of 75 patients were registered ; 71 are included in the analysis . By the criterion of an 80 % prostate-specific antigen reduction maintained for at least 8 weeks , 11 ( 30 % ) of 37 patients in the TEE arm responded , whereas 11 ( 32 % ) of 34 assigned to KA/VE responded . Median survival was 16.9 months ( 95 % confidence interval [ CI ] , 10.5 to 21.2 months ) in the TEE arm and 23.4 months ( 95 % CI , 12.9 to 30.6 months ) for patients treated with KA/VE . Many patients ( 24 % ) failed to complete at least 6 weeks of therapy , including five ( 8 % ) treatment-related early deaths . CONCLUSION Each of these regimens produced clinical ly significant responses , and the observed median survival ( 18.9 months for all 71 patients ) compares favorably with previously published results , especially in the community setting . Nonetheless , it is apparent that these first-generation regimens must be applied judiciously , and thus we view efforts at better patient selection and the development of more tolerable therapies as higher priorities than carrying either of these regimens to phase III evaluation in the cooperative group setting PURPOSE To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer . PATIENTS AND METHODS A 2 × 2 factorial design was used to test two hypotheses : ( 1 ) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and ( 2 ) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer . With 3,250 patients , a disease-free survival ( DFS ) hazard ratio of 0.82 for each r and omization could be detected with 90 % power with two-sided α = .05 . Overall survival ( OS ) was a secondary outcome . RESULTS Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens . After a median follow-up of 6 years , a significant interaction developed between the two r and omization factors ( DFS P = .024 ; OS P = .010 ) in the 2,716 patients r and omly assigned in the original design , which precluded interpretation of the two factors separately . Comparing all four arms showed a significant difference in OS ( P = .040 ) but not in DFS ( P = .11 ) , with all treatments given once every 2 weeks associated with the highest OS . This difference in OS seemed confined to patients with hormone receptor-negative/human epidermal growth factor receptor 2 ( HER2 ) -negative tumors ( P = .067 ) , with no differences seen with hormone receptor-positive/HER2-negative ( P = .90 ) or HER2-positive tumors ( P = .40 ) . CONCLUSION Patients achieved a similar DFS with any of these regimens . Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor-negative/HER2-negative tumors Fifty-six patients were r and omly assigned to receive either one-day cisplatin , doxorubicin , and cyclophosphamide ( PAC ) chemotherapy ( PAC-I ) or five-day PAC ( PAC-V ) for advanced epithelial ovarian carcinoma . Follow-up has been 120 + months or to death . Ninety-one percent had either suboptimal stage III or stage IV disease and 55 % had grade 2 or 3 lesions . Two patients died of toxicity and were free of disease at autopsy . A third patient died of congestive heart failure with no disease at 103 months . Additionally , eight patients had a negative second-look laparotomy , and three ( 37.5 % ) are alive with no evidence of disease ( NED ) 133 to 144 months after diagnosis . Five patients ( 62.5 % ) died of disease 2 to 123 months after negative second-look . Patients with optimal stage III disease had a longer median progression-free interval ( PFI ) and survival ( 33.3 and 44.5 months , respectively ) than those with suboptimal or stage IV disease ( 16.4 and 22.5 months , respectively ) , and the difference in median PFI is significant ( P less than .02 ) . Patients with ascites at diagnosis had a shorter median PFI and survival ( 14.7 and 18 months ) than those without ascites ( 30.0 and 33.0 months ) . Both differences were significant ( PFI , P less than .04 ; survival , P = .005 ) . PAC produces response rates that are superior to those obtained historically with single-agent alkylating therapy . Late recurrences after negative second-look laparotomy suggest that 5-year survival data may be inadequate in ovarian carcinoma PURPOSE The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival ( DFS ) and secondarily on overall survival ( OS ) in patients with high-risk operable breast cancer . PATIENTS AND METHODS From June 1997 until November 2000 , 604 patients with T1 - 3N1M0 or T3N0M0 tumors were r and omized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of ' intensified ' CMF ( cyclophosphamide 840 mg/m2 , methotrexate 47 mg/m2 and fluorouracil 840 mg/m2 ) ( group A ) , or to four cycles of epirubicin followed by four cycles of CMF , as in group A ( group B ) . All cycles were given every 2 weeks with granulocyte colony-stimulating factor support . RESULTS A total of 595 patients were eligible . Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80 % in group A and 77 % in group B. Survival rates were 93 % and 90 % , respectively . The effect of treatment on the hazard of death was different according to hormonal receptor status . More specifically , in patients with negative receptor status the hazard of death was significantly higher for group B ( hazard ratio 2.42 ) . Both regimens were well tolerated and severe acute side-effects were infrequent . No cases of severe cardiotoxicity or acute leukemia were recorded . CONCLUSIONS The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups . However , our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy Thirty adult patients with non-Hodgkin 's lymphoma were studied to evaluate prospect ively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose ( 200 mg m−2 ) in predicting the later impairment of left ventricular function . Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200 , 400 and 500 mg m−2 . Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10 % units to a final left ventricular ejection fraction ⩽50 % . Twenty-eight patients received doxorubicin ⩾400 mg m−2 and were evaluable for cardiotoxicity . Clinical heart failure developed in two patients ( 7 % ) after a cumulative doxorubicin dose of 500 mg m−2 . Left ventricular ejection fraction decreased more than 10 % absolute ejection fraction units to a final left ventricular ejection fraction ⩽50 % in 10 patients ( 36 % ) . Left ventricular ejection fraction decreased from 56±1.5 % to 53.6±1.5 % ( P=0.016 ) in patients with no cardiotoxicity , and from 60.8±2.4 % to 41.8±2.0 % ( P<0.001 ) in patients with cardiotoxicity . For patients who developed cardiotoxicity , the fall in left ventricular ejection fraction after a cumulative doxorubicin dose of only 200 mg m−2 was highly significant ( left ventricular ejection fraction 49.7±1.8 % , P=0.001 vs baseline ) . In receiver operator characteristic analysis , the area under the curve for the decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 200 mg m−2 for predicting cardiotoxicity in all patients was 0.858 . The decrease in left ventricular ejection fraction of more than 4 % units after a cumulative doxorubicin dose of 200 mg m−2 had a 90 % sensitivity and 72 % specificity for predicting later cardiotoxicity . Our results show that the significant impairment of left ventricular function during doxorubicin therapy can be predicted early , already at low cumulative doxorubicin doses . This finding may be of value in identifying patients at high or low risk for the development of anthracycline cardiotoxicity BACKGROUND Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer . The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II ( axillary lymph node-positive ) breast cancer . METHODS Within 6 weeks of surgery ( radical mastectomy , modified radical mastectomy , or lumpectomy ) , 1550 patients with unilateral breast cancer were r and omly assigned to one of three treatment arms : high- , moderate- , or low-dose intensity . The patients received cyclophosphamide , doxorubicin , and 5-fluorouracil on day 1 of each chemotherapy cycle , with 5-fluorouracil administration repeated on day 8 . The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm . The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose . Disease-free survival and overall survival were primary end points of the study . RESULTS At a median follow-up of 9 years , disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm ( two-sided P<.0001 and two-sided P = .004 , respectively ) , with no difference in disease-free or overall survival between the moderate- and the high-dose arms . At 5 years , overall survival ( average + /- st and ard error ) is 79 % + /- 2 % for patients on the high-dose arm , 77 % + /- 2 % for the patients on the moderate-dose arm , and 72 % + /- 2 % for patients on the low-dose arm ; disease-free survival is 66 % + /- 2 % , 61 % + /- 2 % , and 56 % + /- 2 % , respectively . CONCLUSION Within the conventional dose range for this chemotherapy regimen , a higher dose is associated with better disease-free survival and overall survival One hundred patients with non-small cell lung cancer were entered into a r and omized evaluation of two schedules of doxorubicin combined with ftorafur , cyclophosphamide , and cisplatin ( FACP ) . Doxorubicin was given either weekly at 20 mg/m2 , or every three weeks ( st and ard ) at 60 mg/m2 . Fifty-two patients were r and omized to the FACP/weekly doxorubicin arm and 48 patients to the FACP/st and ard doxorubicin arm . The FACP/weekly doxorubicin regimen was associated with higher complete and partial remission rates ( 31 % versus 19 % ) , longer response duration ( median , 33 versus 21 weeks ) , and longer survival duration for responders ( median , 58 versus 50 weeks ) . These differences were not significant . Less neutropenia ( p = 0.01 ) and less infectious morbidity ( p = 0.05 ) were observed in the FACP/weekly doxorubicin arm . Twenty-eight patients underwent 35 endomyocardial biopsies to assess doxorubicin-induced cardiotoxicity . Sixteen biopsies were performed in 12 patients receiving cumulative doxorubicin doses ranging from 250 to 1,190 mg/m2 within the FACP/weekly doxorubicin arm . Nineteen biopsies were performed in 16 patients receiving cumulative doxorubicin doses ranging from 250 to 540 mg/m2 within the FACP/st and ard doxorubicin regimen . The FACP/weekly doxorubicin regimen was associated with significantly lower cardiotoxicity scores ( p = 0.01 ) . This study indicates that weekly administered doxorubicin is as effective and less cardiotoxic than the st and ard schedule PURPOSE Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug , but mechanisms of cardiotoxicity are different in children . We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin . PATIENTS AND METHODS In a r and omized study , children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2 ) in 30-mg/m(2 ) doses every 3 weeks either by bolus ( within 1 hour , n = 57 ) or by continuous infusion ( over 48 hours , n = 64 ) . Echocardiograms obtained before doxorubicin and at longest follow-up times were central ly remeasured , and z scores of cardiac measurements were calculated based on a healthy population . RESULTS The groups were similar in age , sex distribution , doxorubicin dose , and duration of follow-up . Before treatment , measures of left ventricular ( LV ) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups . The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic , but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline . For example , the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms . LV contractility was depressed in both groups ( for bolus patients , median z score = -0.70 SD , P = .006 ; for continuous-infusion patients , median z score = -0.765 , P = .005 ) . Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups . Clinical cardiac manifestations and event-free survival did not differ . CONCLUSION Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion . Both regimens were associated with progressive sub clinical cardiotoxicity . Other cardioprotective strategies should be explored In order to evaluate the possible cardiosparing effect of a prolonged infusion of doxorubicin as compared with the st and ard mode of administration 62 consecutive patients with metastatic carcinoma of the breast or carcinoma of the ovary Stage III or IV were prospect ively r and omized to receive doxorubicin either as a rapid infusion over 15 to 20 minutes at 8 AM or as a continuous infusion over 6 hours , 8 AM to 2 PM . The remaining protocol was identical for the two groups . The cardiotoxic effect of doxorubicin was evaluated by history and physical examination and by the decline in resting ventricular ejection fraction ( LVEF ) as determined by gated pool radionuclide angiography with technetium 99 m ( 99mTc ) and by the decline in the height of the QRS complexes in the st and ard leads of the echocardiogram ( ECG ) . Initially there were 31 patients in each group . The cumulative dose of doxorubicin , was 410 mg/m2 ± 42 SD in the st and ard infusion group and 428 mg/m2 ± 48 SD in the 6‐hour infusion group . The mean decline in LVEF after a cumulative doxorubicin dose of 300 mg/m2 was 17 % in the first group and only 4.1 % in the second . After 400 mg/m2 the mean fall in LVEF was 21 % in the first group and 6 % in the second . The mean decline in QRS voltage after 300 mg/m2 was 29 % and 1.5 % , respectively . Four patients , all in the st and ard infusion group , developed congestive heart failure . These data suggest that slow infusion of doxorubicin is associated with reduced cardiotoxicity A prospect i ve r and omized study was done to determine the effect of different doxorubicin ( Adriamycin [ ADR ] , Adria Laboratories , Columbus , OH ) administration ( schedules every week versus every 3 weeks ) on the productivity of a cyclophosphamide , ADR , cisplatin ( CAP ) chemotherapy regimen for patients with non‐small cell lung cancer ( NSCLC ) . Electrocardiograms , multigated cardiac scans , echocardiograms , and endomyocardial biopsies were done serially for cardiac monitoring . Of 102 patients , 47 had inoperable limited disease ( LD ) , 47 had extensive disease ( ED ) , and eight had no evidence of disease . In the last group chemotherapy was given adjuvantly . Fifty‐one patients were entered into each treatment arm . The groups were formed according to extent of disease and were comparable in terms of patient characteristics . In these groups , the overall response rates using both schedules in LD patients were similar : in patients without chest irradiation previously , there was a response of 35 % with ADR weekly , and 31 % with ADR triweekly ; in LD patients with chest irradiation previously , the response was 20 % with ADR weekly , and 25 % with ADR triweekly ; and in ED patients , 16 % with ADR weekly , and 11 % with ADR triweekly . There was no significant difference in survival between the two treatment groups . However , results for all responders suggested a longer duration of response with weekly than with triweekly ADR ( complete plus partial response : 35.8 versus 11A weeks , P = 0.06 ; minor response : 34 versus 11.5 weeks , P = 0.003 , respectively ) . Results also suggested that weekly ADR was less cardiotoxic than triweekly ADR : 29 % of patients in the former group had no changes or only minor changes in endomyocardial biopsy results , whereas all patients in the latter group had at least grade 0.5 changes at a similar dosage . The median doses of weekly ADR were higher at the same endomyocardial biopsy‐defined toxicity levels . No correlation was found between toxic effects defined by endomyocardial biopsy results and those defined by noninvasive monitoring techniques , although the number of patients assessed was small . Weekly ADR produced less granulocytopenia and a lower incidence of fever ( 6 % versus 16 % , P < 0.001 ) than did triweekly ADR . Alopecia , nausea , vomiting , and diarrhea were significantly less for weekly ADR than triweekly Adr ( P < 0.0005 , < 0.0005 , and < 0.005 , respectively ) . These data suggest that weekly ADR can achieve the same therapeutic results as the st and ard triweekly regimen with less cardiotoxicity , myelotoxicity , alopecia , diarrhea , nausea , and vomiting in patients with NSCLC BACKGROUND Daunorubicin ( DNR ) is one of the most important drugs in treatment of acute lymphoblastic leukemia ( ALL ) . Prolonged infusions of anthracyclines are less cardiotoxic but it has not been investigated whether the in vivo leukemic cell kill is equivalent to short-term infusions . PROCEDURE In the cooperative treatment study COALL-92 for childhood ALL 178 patients were r and omized to receive in a therapeutic window a single dose of 36 mg/m ( 2 ) DNR either as a 1-h ( 85 patients ) or 24-h infusion ( 93 patients ) . Daily measurements of white blood cell count ( WBC ) and peripheral blood smears for seven days could be evaluated central ly in 101 patients ( 1-h : 43 patients , 24-h : 58 patients ) . RESULTS The proportional decline of blasts at day 7 after DNR infusion showed no statistically significant difference between the two treatment arms . At day 3 the median percentage of blasts was less than 10 % , at day 7 less than 2 % for either the 1-h or 24-h infusion . Twelve patients ( 1-h : 5 patients , 24-h : 7 patients ) had an absolute number of more than 1000 blasts per mul peripheral blood ( PB ) at day 7 after DNR infusion ( DNR poor responders ) . Kaplan-Meier analysis showed an equal probability of EFS for the short- and long-term infusion group ( 24-h : 83%+/-5 ; 1-h : 81+/-6 ) after a median observation time of 12.3 years . CONCLUSIONS We conclude that in children with ALL a 24-h infusion of DNR has the same in vivo cytotoxicity for leukemic cells as a 1-h infusion . This offers the possibility to use prolonged infusions with hopefully less cardiotoxicity without loss of efficacy Background : To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens . Patients and Methods : A prospect i ve study including 29 patients who were treated with doxorubicin-containing regimens . Cardiac evaluation was based on 24-hour electrocardiographic monitorization ( Holter ) , which was performed during the first cycle of doxorubicin-containing regimens , as well as after the last cycle of chemotherapy . Results : The mean age of the patients was 45.8 ± 15.1 ( range 18–69 ) . Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients ( 65.5 % ) and in 18 ( 62.1 % ) patients after completion of therapy . One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated . The patient subsequently underwent permanent pacemaker implantation . Conclusions : Doxorubicin may result in arrhythmias both in early and late periods of treatment . These arrhythmias are rarely life threatening Background . Improved survival of children with acute lymphoblastic leukemia ( ALL ) has made it more difficult to develop new protocol s to further improve results . The authors report the pilot experience with the Memorial Sloan‐Kettering‐New York‐II ( MSK‐NY‐II ) protocol , based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity The results of a clinical trial involving 599 patients with inoperable squamous cell , large cell anaplastic , and adenocarcinoma of the lung are summarized . Patients were r and omized to initial therapy with Cytoxan ( CTX ) ( cyclophosphamide ) , or to one of two schedules of Adriamycin ( doxorubicin ) 50 , or 75 mg/m2 IV every three weeks , or to a combined regimen of ADR and CTX . Upon disease progression , CTX patients were r and omized to one of the two ADR schedules , while ADR patients were r and omly assigned to CTX alone , or in combination with Cisdiamminedichloroplatinum ( Cis‐Platinum ) 15 mg/m2 IV every three weeks . No statistically significant response or survival differences were observed between the two dose schedules of Adriamycin for any of the cell types studied . The two dose levels did , however , differ with respect to toxicity . There were some response and survival differences among the various cell types in the comparison of low‐dose Adriamycin and Cytoxan : ( 1 ) patients with adenocarcinoma treated with low‐dose Adriamycin tended to survive longer ( P = 0.04 ) than those treated with Cytoxan ; and ( 2 ) patients with large cell carcinoma receiving Cytoxan experienced a greater tumor response rate than those receiving low dose Adriamycin ( P = 0.03 ) . Because of the difficulties involved in distinguishing these two cell types on pathologic examination , the evidence of apparent treatment differences should not be regarded as definitive . During the period when Adriamycin plus Cytoxan was open to patient entry 61 evaluable patients received that regimen , 21 received low‐dose Adriamycin and 22 received Cytoxan . Because relatively few patients received the latter two regimens , comparisons of these treatments with Adriamycin plus Cytoxan lack statistical power . However , there is no suggestion in the available data that Adriamycin plus Cytoxan increased survival either in the overall population or in the subset of patients with squamous histology . Initial performance status , metastatic disease symptoms , primary disease symptoms , and weight loss were significantly correlated to survival time , and are recommended as stratification factors in future studies PURPOSE To assess the incidence of long-term toxicity after postmastectomy radiation and doxorubicin-based adjuvant chemotherapy . METHODS Records of 470 patients treated with mastectomy , doxorubicin-based chemotherapy , and postmastectomy radiation in five institutional prospect i ve trials were retrospectively review ed . Actuarial toxicity rates were compared with those of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy who did not receive postmastectomy radiation . For those treated with radiation , the chest wall received a median dose of 55 Gy with Co-60 ( 42 % ) or electrons ( 51 % ) . Adjuvant chemotherapy consisted of a doxorubicin-based regimen , often followed by 2 years of cyclophosphamide , methotrexate , and fluorouracil . RESULTS Median follow-up was 10 years . The overall 10-year actuarial rates of RTOG toxicity Grade > 1 and > or=3 after radiation were 4 % and 2 % , respectively . The overall 10- and 15-year actuarial rates of second non-breast cancer malignancy were 3.8 % and 7 % , respectively . There was no statistical difference between the rates of non-breast cancer second malignancy in the radiated and unirradiated cohorts ( 3.4 % vs. 4.7 % 10-year actuarial rates ) . Increasing age and treatment with > 10 cycles of chemotherapy were associated with higher rates of second malignancy ( p = 0.025 , p = 0.016 ) . The 10-year actuarial rate of death from myocardial infa rct ion ( MI ) was 2.4 % ( eight events ) and 0.5 % ( five events ) in the radiated and unirradiated groups , respectively ( p = 0.058 ) . Of the 8 irradiated patients who died of MI , 2 patients had left-sided breast cancer . CONCLUSIONS We found very low rates of serious sequelae after postmastectomy radiation , including death from myocardial infa rct ion and non-breast cancer second malignancy . The rate of second non-breast cancer malignancy was increased among patients treated with > 10 cycles of cyclophosphamide-containing chemotherapy PURPOSE To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel ( Taxotere ; Rhône-Poulenc Rorer , Collegeville , PA ) as primary chemotherapy of breast cancer . PATIENTS AND METHODS Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were r and omly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery . Patients in arm A received sequential therapy with doxorubicin 75 mg/m(2 ) every 2 weeks for three cycles followed by docetaxel 100 mg/m(2 ) every 2 weeks for three cycles . Patients in arm B received combination therapy with doxorubicin 56 mg/m(2 ) plus docetaxel 75 mg/m(2 ) every 3 weeks for four cycles . Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups . RESULTS Forty patients were entered onto the trial . Pretreatment tumor size averaged 5.7 cm with clinical ly positive axillary lymph nodes in 23 patients ( 57 % ) . As expected , myelosuppression was severe in both groups ; however , > /= 80 % of planned dose-intensity was delivered . H and -foot syndrome was more common after sequential therapy . Clinical responses were similar in both groups , with an overall response rate of 87 % , including 20 % clinical complete remissions . Pathologic complete remission or residual in situ disease only was confirmed in five patients ( 12.8 % ) . Patients who received sequential therapy had fewer positive lymph nodes ( mean , 2.17 v 4.81 ; P < .037 ) at definitive surgery . CONCLUSION Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active . A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy Doxorubicin ( Adriamycin ) was administered by continuous infusion to reduce peak plasma levels and thus lessen cardiac toxicity . Cardiotoxicity was monitored by noninvasive methods , and endomyocardial biopsy specimens were studied by electronmicroscopy . Cardiotoxicity was compared in 21 patients receiving doxorubicin intravenously over 48 or 96 hours and in 30 control patients treated by st and ard intravenous injection . Both groups were studied prospect ively and were well matched by risk factors for doxorubicin cardiotoxicity . The median cumulative dose for those receiving continuous infusion was 600 mg/m2 body surface area ( range , 360 to 1500 mg/m2 ) compared with 465 mg/m2 ( range 290 to 680 mg/m2 ) in the control group ( p = 0.002 ) . Fourteen of the 30 patients in the control group showed severe morphologic changes in the biopsy specimens , precluding further doxorubicin administration , as compared with two of 21 patients receiving the drug by continuous infusion ( p less than 0.02 ) . The mean pathologic score for the infusion group , 0.9 , was lower than the mean for the control group , 1.6 ( p = 0.004 ) . Antitumor activity was not compromised . Decreasing peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity Two hundred eleven patients with advanced breast cancer were r and omized to receive either epirubicin ( E ) 50 mg/m2 and prednisolone ( LEP ) or E 100 mg/m2 and prednisolone ( HEP ) . The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals . Reasons for stopping treatment early included progressive disease , stable disease without symptomatic improvement , or severe toxicity deemed intolerable by either the patient or physician . Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization ( WHO ) criteria of response and toxicity . Two hundred nine patients were eligible for analysis , 98 % of whom have been followed for more than a year . One hundred four patients received LEP and 105 HEP . Significantly worse myelosuppression , alopecia , nausea and vomiting , and mucositis were seen in the high-dose arm ( P less than or equal to .001 ) . More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm , and the commonest reason for stopping was progressive disease . A similar median number of courses was given in each arm . There was a significantly higher response in the HEP arm ( HEP - complete response [ CR ] + partial response [ PR ] = 41 % , LEP - CR + PR = 23 % ) . Despite this , no statistically significant differences was seen in overall survival or progression-free interval . The median survival for HEP and LEP was 44 and 46 weeks , respectively We report the first r and omized study assessing the efficacy and safety of daunorubicin ( DNR ) continuous infusion ( CI ) compared to the more conventional 30-min infusion ( i.v . ) in newly diagnosed adult acute lymphoblastic leukemia ( ALL ) . Seventy-seven patients were initially r and omized to receive either a 24-h CI DNR ( 60 mg/m2 days 2–4 ) ( 40 patients ) or bolus DNR at the same dosage ( 37 patients ) with vincristine ( 2 mg i.v . days 1 , 8 , 15 ) and oral prednisone ( 60 mg/m2 days 1–15 ) , without hematopoietic growth factor support , as an induction regimen . The distribution of adverse prognostic factors was comparable in the two-induction arm . Acute toxicity was more important in the CI arm . Gram negative infection ( 9 vs 1 gram negative septicemia , P = 0.01 ) and infection-related deaths ( 6 vs 1 deaths , P = NS ) occurred more frequently in the CI arm during the induction treatment than in the i.v . arm , leading to the study interruption . Neutropenia but not thrombopenia duration was significantly longer in the CI arm than in the i.v . arm ( 18 days vs 14 days , P > 0.05 and 16 days vs 12 days , P > 0.05 , respectively ) . Despite a similar CR rate according to the method of DNR administration ( 68 % in the CI DNR arm vs 76 % in the i.v . arm after the first course ) , there was a trend toward higher freedom from relapse ( FFR ) after DNR CI ( 48 % vs 28 % in the i.v . arm at 5 years , P = NS ) , suggesting that despite this high toxicity , DNR CI may improve the CR quality and decrease further the residual disease To assess myocardial cell damage due to doxorubicin cardiotoxicity , we prospect ively studied 30 patients with sarcomas who were receiving chemotherapy , including doxorubicin . Sixteen patients were treated by continuous infusion over 72 hr and 14 patients were treated by bolus injection . Antimyosin studies and left ventricular ejection fraction ( LVEF ) measurements were performed before chemotherapy and at intermediate and maximal cumulative doses . Myocardial antimyosin uptake was quantified by a heart-to-lung ratio ( HLR ) . Myocardial antimyosin uptake was observed in all patients at 240 - 300 mg/m2 when ejection fraction was still maintained . Seven patients presented with a decrease of > or = 10 % in absolute ejection fraction units at 420 - 600 mg/m2 . Five of these patients had mild congestive heart failure . All patients who presented with a decrease in LVEF > or = 10 % at 420 - 600 mg/m2 had increased antimyosin uptake with HLR > or = 1.90 at a cumulative dose of 240 - 300 mg/m2 . Patients who were treated with continuous infusion had less antimyosin uptake than those who were treated with bolus administration ( mean HLR of 1.70 + /- 0.09 versus HLR of 2.01 + /- 0.16 at a cumulative dose of 240 - 300 mg/m2 , p < 0.01 ; HLR of 1.86 + /- 0.12 versus HLR of 2.32 + /- 0.34 at a cumulative dose of 420 - 600 mg/m2 , p < 0.01 ) . Two of 16 patients treated by continuous infusion and 5 of 14 patients treated by bolus injection presented with a decrease in ejection fraction > or = 10 % . LVEF after chemotherapy in the infusion group was 56 % + /- 5 % and 48 % + /- 8 % ( p < 0.05 ) in the bolus group . Antimyosin studies are helpful in the assessment of doxorubicin cardiotoxicity . Intense antimyosin uptake at intermediate cumulative doses identifies patients at risk of cardiotoxicity before ejection fraction deteriorates . Patients with sarcomas treated by continuous infusion present with less antimyosin uptake than those treated with bolus injection , indicating less severe cardiotoxicity PURPOSE A potential application of hematopoietic growth factors is to obtain an increased dose-intensity . This can be achieved by either higher doses of chemotherapy with st and ard intervals , or by st and ard doses with shorter intervals . The potential of these approaches has not been investigated systematic ally . PATIENTS AND METHODS In a r and omized , multicenter study , 49 advanced breast cancer patients were treated with granulocyte colony-stimulating factor ( G-CSF ) and either increasing doses of epirubicin and cyclophosphamide with fixed intervals ( arm one ) or progressively shorter intervals with fixed doses of epirubicin and cyclophosphamide ( arm two ) . A cohort of at least six patients was studied at each interval/dose . A more intensified interval/dose was given if less than 50 % of patients encountered a dose-intensity limiting criterium ( DILC ) in the first three courses . RESULTS In arm one , epirubicin 140 mg/m2 and cyclophosphamide 800 mg/m2 every 21 days was too toxic . Subsequently , epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 was tested with two of 10 patients encountering a DILC . All initial DILCs consisted of febrile neutropenia . In arm two , epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely with 14- and 12-day intervals . In the 10-day interval , eight of 12 patients completed the first three cycles without a DILC . In the 8-day interval , seven of eight patients encountered a DILC . Incomplete neutrophil recovery , and to a lesser extent stomatitis , were dose-limiting . CONCLUSION In combination with G-CSF , epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 every 21 days was feasible ( projected dose-intensity , 40 mg/m2/wk and 233 mg/m2/wk , respectively ) . Epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely every 10 days , allowing a projected dose-intensity of 52.5 mg/m2/wk and 350 mg/m2/wk , respectively PURPOSE We conducted a phase III r and omized study of two adjuvant treatment schedules of doxorubicin ( A ) and cyclophosphamide ( C ) in early-stage breast cancer to determine if administration of sequential single agents ( A -- > C ) results in superior disease-free survival ( DFS ) and overall survival ( OS ) versus the same total dose given in combination ( AC ) . PATIENTS AND METHODS High-risk node-negative or low-risk node-positive breast cancer patients received AC given : ( arm I ) concurrently ( AC ) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously ( IV ) every 3 weeks for six cycles ; or ( arm II ) in sequence ( A C ) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cycles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles . Total dose and duration were identical , but the intensity of each drug was increased on A C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics . All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy . RESULTS Between 1994 and 1997 , 3,176 patients were r and omly assigned . Arms were well balanced ; 48 % of eligible patients were node-negative and 48 % were estrogen receptor-positive . No significant differences in OS or DFS were observed ; 5-year estimates of OS ( 95 % CI ) were 88 % ( 87 % to 90 % ) on AC and 89 % ( 87 % to 91 % ) on A -- > C. Grade 4 hematologic toxicity was greater on A -- > C , but nonhematological grade 4 was similar . CONCLUSION The overall result does not support superiority of dose-intense sequenced single agents . The greater toxicity of higher doses of single agents does not support their sequential use AIM Monitoring of cardiotoxicity of conventional and high-dose chemotherapy ( HD-CT ) with multiple biomarkers of cardiac injury - glycogen phosphorylase BB ( GPBB ) , heart-type fatty acid binding protein ( H-FABP ) , cardiac troponins ( cTnT , cTnI ) , creatine kinase MB ( CK-MB mass ) , myoglobin . METHODS A total of 47 adult acute leukemia patients were studied - 24 patients treated with conventional CT containing anthracyclines ( ANT ) and 23 patients treated with HD-CT ( myeloablative preparative regimen ) followed by hematopoietic cell transplantation ( HCT ) . Cardiac biomarkers were assessed prior to treatment ( before CT/HD-CT ) , after first CT with ANT , after last CT with ANT in the first group , after HD-CT and after HCT in the second group . Values above the reference range were considered elevated . RESULTS Before CT/HD-CT , all biomarkers of cardiac injury were below the cut-offs in all patients . GPBB increased above the cut-off ( 7.30 microg/L ) in 4 ( 16.7 % ) patients after first CT and in 5 ( 20.8 % ) patients after last CT with ANT . GPBB increased above the cut-off in 5 ( 21.7 % ) patients after HD-CT and remained elevated in 5 ( 21.7 % ) patients after HCT . CTnI became elevated ( above 0.40 microg/L ) in 2 ( 8.3 % ) patients after first and last CT with ANT . Both patients with cTnI positivity had elevated GPBB . Other tested biomarkers remained below the cut-offs during the study . CONCLUSION Our results suggest that GPBB could become a sensitive biomarker for detection of acute cardiotoxicity associated with conventional CT containing ANT and HD-CT followed by HCT . The predictive value for development of cardiomyopathy in the future is not known and should be evaluated during a prospect i ve follow-up . Based on our data , a larger prospect i ve and multicenter study would be most desirable to define the potential role of new circulating biomarkers in the assessment of cardiotoxicity in oncology The severity of late cardiotoxicity after anthracycline treatment for childhood cancer relates mainly to the cumulative anthracycline dose received , but all dose ranges cause some cardiac dysfunction . Anthracycline administration by infusion in order to lower peak drug concentration has been used in an attempt to reduce cardiotoxicity . Cardiac performance was assessed by echocardiography in children who were relapse‐free survivors of treatment for acute lymphoblastic leukaemia ( ALL ) . They received the same cumulative anthracycline dose ( daunorubicin 180 mg/m2 ) either by bolus injection ( UKALL X protocol , n = 40 ) or by infusion ( UKALL XI protocol , n = 71 ) with a follow‐up duration of 5·3 ± 2·0 and 5·4 ± 1·0 years respectively . On analysis , both the bolus administration and infusion groups showed similar mild impairment of cardiac performance , characterized by increased left ventricular end systolic stress and impaired left ventricular function . In conclusion , sub clinical abnormality of left ventricular performance was confirmed in both groups despite the relatively modest cumulative anthracycline dose received . We were unable to demonstrate an advantage of anthracycline administration by 6‐h infusion with respect to late cardiotoxicity at this dose BACKGROUND This post-hoc analysis aim ed to compare an intense dose-dense sequential chemotherapy ( DD-CT ) and a conventionally-dosed chemotherapy ( CD-CT ) in the neoadjuvant AGO-1 study , focusing on the subgroup with inflammatory breast cancer ( IBC ) . PATIENTS AND METHODS Out of 668 r and omised patients , 101 patients presented with IBC . Patients received epirubicin followed by paclitaxel every 2 weeks ( DD-CT ) or simultaneously every 3 weeks ( CD-CT ) . RESULTS No differences in pathological complete response rates were observed [ odds ratio (OR)=1.27 , p=0.33 ] . Most patients were scheduled for mastectomy before starting therapy ; however , in 21.7 % breast-conserving surgery was performed . Disease-free survival rates [ Hazard Ratio (HR)=0.65 ; p=0.597 ] and overall survival rates ( HR=1.40 ; p=0.327 ) were similar for both treatment arms . Patients with breast-conserving surgery had a significantly better outcome than patients treated with mastectomy ( disease-free survival : HR=0.41 ; p=0.034 and overall survival : HR=0.09 ; p=0.003 ) . CONCLUSION Patients with IBC benefited not from DD-CT but from breast-conserving surgery after neoadjuvant chemotherapy BACKGROUND Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival . Some clinicians seek a greater survival benefit by increasing the intensity of the dose , whereas others lower it to diminish toxicity . METHODS The Cancer and Leukemia Group B ( CALGB ) conducted a r and omized trial of different levels of doses and dose intensity ( dose per unit of time ) of adjuvant chemotherapy in 1572 women with node-positive , stage II breast cancer who were assigned to three treatment groups . One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days , for six cycles . Another group received 50 percent higher doses of the three drugs ( 600 mg , 60 mg , and 600 mg , respectively ) but for only four cycles , so that the total dose was identical in these two groups but the dose intensity was higher in the first . The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group . RESULTS After a median of 3.4 years of follow-up , the women treated with a high or moderate dose intensity had significantly longer disease-free survival ( P < 0.001 ) and overall survival ( P = 0.004 ) than those treated with a low dose intensity , in three-way log-rank comparisons . However , the difference in survival between the two groups treated with a moderate or high dose intensity was not significant . These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity . CONCLUSIONS The doses of chemotherapy used to treat breast cancer , especially early breast cancer , should not be reduced if the maximal benefit is to be achieved Echocardiography is a sensitive method for detecting wall motion abnormalities , as well as for monitoring cardiotoxicity during treatment with anthracyclines . Using echocardiography , this study investigated possible acute cardiotoxicty associated with primary treatment of Hodgkin 's disease according to German Hodgkin 's Lymphoma Study Group ( GHSG ) clinical trial protocol s for adults . A group of 88 patients ( 48 men ) was registered in the prospect i ve , r and omized clinical trial involving the treatment of Hodgkin 's disease using third and fourth generation GHSG protocol s. These patients were monitored by echocardiography . The average age was 34 years ( range , 18 - 65 ; median , 32 ) . The average anthracycline dose was 174 mg/m2 ( median 200 mg/m2 ) , and the average mediastinum irradiation dose was 21 Gy ( median 30 Gy ) . Left ventricle end-systolic diameter ( ESD ) and left ventricle end-diastolic diameter ( EDD ) , as well as fractional shortening ( FS ) and ejection fraction ( EF ) ( M-mode calculation ) were evaluated , as was the presence of pericardial effusion and wall motion abnormalities . The examinations were conducted before and at the end of therapy ( up to 2 months ) . Results show that all evaluated parameters changed from one follow-up examination to the other , but these changes did not reach statistical significance . ESD increased from 30 + /- 4 to 31 + /- 4 mm . EDD increased from 49 + /- 4 to 49 + /- 5 mm . Ejection fraction changed from 69 + /- 7 to 66 + /- 7 % and fractional shortening was unchanged ( from 38 + /- 7 to 38 + /- 7 % ) . In seven patients ( 8 % ) , we observed new wall motion abnormalities characterized by hypokinesis without decrease of left ventricular function . Significant changes in the amount of pericardial effusion were not observed . In four patients ( 5 % ) , there was progression of Hodgkin 's disease . In conclusion , treatment according to third and fourth generation clinical trial protocol s of the GHSG leads only to minimal wall motion changes , without concomitant reduction of left ventricular function , thus not meeting the criteria , acute cardiotoxicity Disseminated soft-tissue sarcomas are a group of uncommon malignancies generally treated in a uniform manner . This study question ed the impact of schedule on response rate and toxicity in patients with metastatic soft-tissue sarcoma treated with the two-drug combination doxorubicin and dacarbazine . Patients were r and omly assigned to receive either bolus therapy with doxorubicin at a dose of 60 mg/m2 and dacarbazine at a dose of 750 mg/m2 intravenously on day 1 ( 118 patients ) or infusional therapy with doxorubicin at 60 mg/m2 and dacarbazine at 750 mg/m2 delivered by continuous intravenous infusion for 96 hours on days 1 - 4 ( 122 patients ) . Chemotherapy was to be repeated every 3 weeks . A unique feature of this cooperative group protocol was a provision for surgical resection of residual disease in patients with a partial response or with stable disease following chemotherapy . Similar overall response rates ( 17 % in both treatment arms ) and complete response rates ( 5 % in both treatment arms ) were observed . For patients receiving bolus therapy , the median response duration was 19.6 months for those in complete remission and 6.6 months for those in partial remission . For patients receiving infusional therapy , the median response duration was 12.6 months for those in complete remission and 9.3 months for those in partial remission . Examination of dose intensity received when combining treatment arms revealed a weak doxorubicin dose-response relationship . There was no difference in median survival times between the two treatment arms ( bolus therapy , 10.6 months ; infusional therapy , 10.5 months ; logrank P = .97 ) . Analysis of toxic effects favored infusional therapy . Significant reductions in cardiac toxicity ( all events , P = .04 ; clinical events , P = .01 ) and nausea and emesis ( P = .04 ) were seen in infusional therapy . Of 47 patients eligible for cytoreductive surgery following chemotherapy , 12 received surgery , and of those 12 , eight were rendered disease free . The use of a 96-hour continuous intravenous infusion of doxorubicin-dacarbazine was comparable therapeutically with bolus dosing of these two agents and was better tolerated by the patients Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug . A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7 % of patients developed doxorubicin‐related congestive heart failure ( CHF ) after a cumulative dose of 550 mg/m2 . To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting , the authors evaluated data from three prospect i ve studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs BACKGROUND Anthracyclines are effective antineoplastic drugs in acute myelogenous leukemia ( AML ) . However , their use is limited by cardiomyopathy , which occurs in children already at cumulative doses of 300 mg/m(2 ) ( given as daunorubicin equivalent ) . PROCEDURE To evaluate anthracycline-associated cardiomyopathy in pediatric AML- patients , the incidence of early and late ( > 1 year after intensive AML chemotherapy ) clinical and sub clinical cardiotoxicity was analyzed out of a total of 1,207 patients < 18 years treated between 1993 and 2003 in trials AML-BFM93/98 : 1,010 protocol patients with de novo AML , 121 with Down syndrome (DS)-AML , and 76 with secondary AML . The cumulative dose of anthracyclines was generally risk-adapted : 300 - 450 mg/m(2 ) using 1 - 4-hr infusions of anthracyclines with the assumed lowest cardiotoxic potential . Eight hundred eighty-five patients ( 73 % ) were eligible for the analysis of early and 547 ( 45 % ) of late cardiotoxicity ( 1,399 follow-up data ) . RESULTS Thirty-eight patients ( 4.3 % ) , including 3 DS-AML and 1 secondary AML , suffered from early cardiomyopathy . After 5 years , four patients showed temporarily or persistently a reduced shortening fraction , which led to death in one DS-AML patient . Including these 4 patients , late cardiomyopathy was seen in 16 patients ( cumulative incidence after 11 years : 5 % + /- 1 % ) . Nine patients ( 2.5 + /- 1 % ) showed clinical symptoms , five of them had persistent abnormal shortening fraction . Late sub clinical cardiomyopathy occurred temporarily in seven patients . Late clinical cardiomyopathy mainly affected patients with a second anthracycline therapy ( secondary malignancy ) and those with early cardiotoxicity . CONCLUSION In spite of a highly intensive and effective treatment , the frequency of anthracycline-associated cardiomyopathy was low in the AML-BFM studies Liposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells . On the basis of doxorubicin 's demonstrated clinical efficacy against hormone‐refractory prostate carcinoma ( HRPCA ) , the authors conducted a prospect i ve , r and omized Phase II clinical trial to evaluate the feasibility , toxicity , and therapeutic efficacy associated with the pegylated form of this agent PURPOSE Rituximab with cyclophosphamide , doxorubicin , vincristine , and prednisone ( R-CHOP ) is one of the most effective front-line therapies to treat indolent B-cell lymphoma . Granulocyte colony-stimulating factor ( G-CSF ) , which potentiates antibody-dependent rituximab cytotoxicity , is used to shorten CHOP intervals . To improve progression-free survival ( PFS ) in patients treated with R-CHOP as the primary end point , we conducted a phase III study . PATIENTS AND METHODS Patients with untreated stages III to IV indolent B-cell lymphoma were r and omly assigned to six cycles of R-CHOP every 3 weeks ( R-CHOP-21 ) or every 2 weeks ( R-CHOP-14 ) with G-CSF . Maintenance rituximab was not allowed . RESULTS Three hundred patients were enrolled . At the median follow-up time of 5.2 years , there was no significant difference in PFS between arms for the 299 eligible patients ; the median was 3.7 ( R-CHOP-21 ) v 4.7 ( R-CHOP-14 ) years , 57 % v 58 % at 3 years , and 41 % v 43 % at 6 years , respectively ( hazard ratio [ HR ] , 0.92 ; 95 % CI , 0.68 to 1.25 ; one-sided P = .30 ) . The median overall survival ( OS ) time was not reached in either arm , and there was no significant difference ( 6-year OS : 87 % [ R-CHOP-21 ] v 88 % [ R-CHOP-14 ] ; HR , 1.15 ; 95 % CI , 0.57 to 2.30 ; one-sided P = .65 ) . Although grade 4 neutropenia and grade 3 infections were more frequent in the R-CHOP-21 group , R-CHOP was feasible in both arms . CONCLUSION The R-CHOP dose-dense strategy failed to improve PFS of patients with untreated indolent B-cell lymphoma . Further improvement of first-line treatment or investigations on postremission therapy following R-CHOP should be explored The effect of enhancing the dose intensity ( DI ) of the key drugs in multidrug combination chemotherapy for malignant lymphoma is uncertain . We investigated the survival benefit of dose-intensified multidrug combination chemotherapy for intermediate- or high- grade non-Hodgkin ’s lymphoma ( NHL ) . Patients without any prior chemotherapy were r and omly assigned either to dose-intensified multidrug combination chemotherapy , LSG9 ( VEPA-B/FEPP-AB/M-FEPA , treated 3 times every 10 weeks for 28 weeks total ) , or to control-arm combination chemotherapy , mLSG4 ( VEPA-B/FEPP-B/M-FEPA , treated 4 times every 14 weeks for 54 weeks total ) . The planned DI of doxorubicin and cyclophosphamide were 1.96 and 1.47 times higher , respectively , in LSG9 than in mLSG4 . Overall survival , complete response ( CR ) rate , and toxicities were evaluated . The 447 patients ( 230 for LSG9 and 217 for mLSG4 ) were enrolled between February 1991 and March 1995.The 5-year overall survival rates were 56.8 % for LSG9 patients and 55.1 % for mLSG4 patients ( log-rank P = .42).The rates for CR plus uncertain CR were 70.0 % for LSG9 and 64.5 % for mLSG4 . The toxicities of both regimens were similar and tolerable . The median actual DI of doxorubicin and cyclophosphamide were 1.56 and 1.17 times higher , respectively , in LSG9 than in mLSG4 . Compared with the control regimen mLSG4 , the dose-intensified regimen LSG9 did not show significant survival benefit . An increase in the DI of doxorubicin in multidrug combination chemotherapy did not improve the survival of patients with intermediate- or high- grade NHL Pre clinical studies show that docetaxel ( Taxotere ) and cyclophosphamide ( Cytoxan , Neosar ) are synergistic against MA 13/C mammary adenocarcinoma . Both agents are highly active as monotherapy in a number of tumors , including metastatic breast cancer . Therefore , we performed a phase I dose-finding study to determine the maximum tolerated dose of this combination regimen in patients with advanced solid tumors . A total of 45 patients were enrolled and received cyclophosphamide followed by docetaxel , both administered as 1-hour intravenous infusions once every 3 weeks . The dose levels of cyclophosphamide/docetaxel were 600/60 mg/m2 ( group 0 ) , 600/75 mg/m2 ( group I ) , 700/75 mg/m2 ( group 2 ) , 800/75 mg/m2 ( group 3 ) , 800/85 mg/m2 ( group 4 ) , 800/75 mg/m2 ( group 5 ) , and 800/85 mg/m2 ( group 6 ) . Patients with dose-limiting neutropenia in groups 5 and 6 received 300 micrograms of granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim [ Neupogen ] ) support on days 2 through 9 during subsequent cycles of chemotherapy . All patients received premedication with 8 mg of dexamethasone twice daily for 5 days , beginning 1 day prior to chemotherapy . The dose-limiting toxicity was neutropenia fever . The recommended dose for phase II studies of cyclophosphamide/docetaxel is 700/75 mg/m2 in previously treated patients and 800/75 mg/m2 in previously untreated patients . G-CSF support did not allow for further dose escalation . Preliminary results from this phase I trial indicate that the combination of docetaxel and cyclophosphamide produced an objective response rate of 69 % in 32 patients with metastatic breast cancer ( including 3 patients who achieved complete responses ) Doxil , a doxorubicin formulation of polyethylene glycol-coated liposomes , has anti-tumor activity against Kaposi 's sarcoma and other solid tumors with mild myelosuppression , minimal hair loss and a low risk of cardiotoxicity . Non-liposomal doxorubicin has modest activity in hormone-refractory prostate cancer ( HRPC ) with considerable toxicity . A pilot study of Doxil was conducted in 15 patients with HRPC . Doxil was administered i.v . using two regimes of equal dose intensity , either 45 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks . Plasma levels of doxorubicin were analyzed in 10 patients . The most common side effect was stomatitis with a higher incidence at the 60 mg/m2 dose level . In contrast , h and -foot syndrome was more frequent and severe in patients treated with the 3 week schedule of 45 mg/m2 . Three patients responded to treatment ( based on objective response in one patient and reduction of PSA level greater than 50 % in the other two ) and two patients had stable disease , all of them receiving 60 mg/m2 . Pharmacokinetic analysis shows a proportional increase of plasma drug levels with dose and the characteristic long circulation time of Doxil with half-lives in the range of 3 days , somewhat longer than previously reported . In conclusion , Doxil at 60 mg/m2 every 4 weeks appears to be active against HRPC , but severe mucocutaneous toxicities prevented further investigation of this regime BACKGROUND CHOP-21 has remained the st and ard chemotherapy for aggressive non-Hodgkin 's lymphoma ( NHL ) , and dose intensification is a potential strategy for improving therapeutic results . We conducted a phase III trial to determine whether dose-dense strategy involving interval shortening of CHOP ( CHOP-14 ) is superior to CHOP-21 . PATIENTS AND METHODS A total of 323 previously untreated patients ( aged 15 - 69 years ) with stages II-IV aggressive NHL were r and omized . The primary end point was progression-free survival ( PFS ) . RESULTS Treatment compliance was comparable in both study arms . At 7-year follow-up , no substantial differences were observed in PFS and overall survival ( OS ) between CHOP-21 ( n = 161 ) and CHOP-14 ( n = 162 ) arms . Median PFS was 2.8 and 2.6 years with CHOP-21 and CHOP-14 , respectively ( one-sided log-rank P = 0.79 ) . Eight-year OS and PFS rates were 56 % and 42 % [ 95 % confidence interval ( CI ) 47 % to 64 % and 34 % to 49 % ] , respectively , with CHOP-21 and 55 % and 38 % ( 95 % CI 47 % to 63 % and 31 % to 46 % ) , respectively , with CHOP-14 . Subgroup analyses showed no remarkable differences in PFS or OS for patients stratified as per the International Prognostic Index or by age . CONCLUSION Dose-intensification strategy involving interval shortening of CHOP did not prolong PFS in advanced , aggressive NHL |
2,123 | 26,599,405 | AUTHORS ' CONCLUSIONS There is some , albeit preliminary , evidence that asenapine provides an improvement in positive , negative , and depressive symptoms , whilst minimising the risk of adverse effects .
However due to the low- quality and limited quantity of evidence , it remains difficult to recommend the use of asenapine for people with schizophrenia . | BACKGROUND Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology .
Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration ( FDA ) for the treatment of schizophrenia .
OBJECTIVES To determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo . | OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVE This 6-week trial assessed the efficacy , tolerability , and safety of the investigational psychopharmacologic agent asenapine versus placebo and risperidone in patients with acute schizophrenia ( DSM-IV criteria ) . METHOD In a study conducted from August 2001 to May 2002 , patients were r and omly assigned to receive sublingual asenapine 5 mg b.i.d . , placebo b.i.d . , or oral risperidone 3 mg b.i.d . The primary outcome measure was improvement from baseline in Positive and Negative Syndrome Scale ( PANSS ) total score . Secondary outcomes included changes in Clinical Global Impressions-Severity of Illness ( CGI-S ) score and scores on PANSS positive , negative , and general psychopathology subscales . RESULTS The intent-to-treat population comprised 174 patients who received > or= 1 dose of study drug and > or= 1 postbaseline assessment . At study end or last observation , mean improvements on PANSS total , negative subscale , and general psychopathology subscale scores were all significantly greater with asenapine than with placebo ( p < .005 , p = .01 , and p < .005 , respectively ) . Compared with placebo , improvements on CGI-S and PANSS positive subscale scores were significantly greater with both asenapine ( p < .01 and p = .01 ) and risperidone ( p < .005 and p < .05 ) . Overall incidence rates of adverse events were comparable for asenapine and placebo , whereas risperidone was associated with substantial weight gain and prolactin elevation . CONCLUSION Asenapine was effective and well tolerated in patients with acute schizophrenia and may provide a new option for control of negative symptoms OBJECTIVE Long-term efficacy of asenapine in preventing schizophrenia relapse was assessed in a 26-week double-blind , placebo-controlled trial that followed 26 weeks of open-label treatment . METHOD Stable schizophrenia patients ( DSM-IV-TR criteria ) who were cross-titrated from previous medication to sublingual asenapine and remained stable during 26 weeks of open-label treatment were eligible for 26 weeks of double-blind treatment , with r and omization to continued asenapine or switch to placebo . Time to relapse/impending relapse ( primary endpoint , as usually determined by specific scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of Illness Scale ) and discontinuation for any reason ( key secondary endpoint ) were assessed by survival analyses for asenapine versus placebo . The study was conducted from May 2005 through June 2008 . RESULTS Of 700 enrolled patients treated with open-label asenapine , 386 entered ( asenapine , n = 194 ; placebo , n = 192 ) and 207 completed ( n = 135 ; n = 72 ) the double-blind phase . Times to relapse/impending relapse and discontinuation for any reason were significantly longer with asenapine than with placebo ( both P < .0001 ) . Incidence of relapse/impending relapse was lower with asenapine than placebo ( 12.1 % vs 47.4 % , P < .0001 ) . The modal dosage of asenapine was 10 mg twice daily in both phases . During the double-blind phase , the incidence of adverse events ( AEs ) considered serious with asenapine and placebo was 3.1 % and 9.9 % , respectively ; incidence of extrapyramidal symptom-related AEs was 3.1 % and 4.7 % , respectively . The most frequently reported AEs with asenapine versus placebo were anxiety ( 8.2 % ; 10.9 % ) , increased weight ( 6.7 % ; 3.6 % ) , and insomnia ( 6.2 % ; 13.5 % ) . The incidence of clinical ly significant weight gain ( ≥ 7 % increase from double-blind baseline ) was 3.7 % with asenapine and 0.5 % with placebo . CONCLUSIONS Long-term treatment with asenapine was more effective than placebo in preventing relapse of schizophrenia and appeared to be safe and well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier NCT00150176 BACKGROUND In two double-blind trials conducted in North America , 513 patients with chronic schizophrenia received risperidone , haloperidol , or placebo . In the present study , combined data from the two trials were analyzed . METHOD Patients were r and omly assigned to receive placebo , fixed doses of risperidone ( 2 , 6 , 10 , and 16 mg/day ) or 20 mg/day of haloperidol for 8 weeks . Factor analysis of scores on the Positive and Negative Syndrome Scale ( PANSS ) produced five dimensions ( negative symptoms , positive symptoms , disorganized thought , uncontrolled hostility/excitement , and anxiety/depression ) , similar to the five dimensions of previous factor-analytic studies of PANSS data . RESULTS Mean changes ( symptom reductions ) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6 - 16 mg/day of risperidone than in patients receiving placebo or haloperidol . The advantages of risperidone were greatest for negative symptoms , uncontrolled hostility/excitement , and anxiety/depression . Even at the lowest dose , 2 mg/day , risperidone was significantly ( p < or = .05 ) superior to haloperidol in reducing negative symptoms . The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms . CONCLUSION Risperidone produced significantly ( p < or = .05 ) greater improvements than haloperidol on all five dimensions . The large between-group differences on negative symptoms , hostility/excitement , and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features . In a double-blind 6-week trial , 458 patients with acute schizophrenia were r and omly assigned to fixed-dose treatment with asenapine at 5 mg twice daily ( BID ) , asenapine at 10 mg BID , placebo , or haloperidol at 4 mg BID ( to verify assay sensitivity ) . With last observations carried forward ( LOCF ) , mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID ( −16.2 ) and haloperidol ( −15.4 ) than placebo ( −10.7 ; both P < 0.05 ) ; using mixed model for repeated measures ( MMRM ) , changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID ( −21.3 and −19.4 , respectively ) and haloperidol ( −20.0 ) than placebo ( −14.6 ; all P < 0.05 ) . On the Positive and Negative Syndrome Scale positive subscale , all treatments were superior to placebo with LOCF and MMRM ; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM . Treatment-related adverse events ( AEs ) occurred in 44 % and 52 % , 57 % , and 41 % of the asenapine at 5 and 10 mg BID , haloperidol , and placebo groups , respectively . Extrapyramidal symptoms reported as AEs occurred in 15 % and 18 % , 34 % , and 10 % of the asenapine at 5 and 10 mg BID , haloperidol , and placebo groups , respectively . Across all groups , no more than 5 % of patients had clinical ly significant weight change . Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol ; greater contrasts were seen in AEs , especially extrapyramidal symptoms |
2,124 | 31,719,081 | Combined aerobic and strength training was ranked first for improving both fat mass ( kg ) and per cent body fat while aerobic exercise was ranked first for improving BMI .
Conclusions Aerobic and combined aerobic and strength training are associated with improvements in adiposity outcomes in overweight and obese children and adolescents . | Objectives Determine both the effects and hierarchy of effectiveness for exercise interventions ( aerobic , strength training or both ) on selected measures of adiposity ( body mass index ( BMI ) in kg/m2 , fat mass and per cent body fat ) in overweight and obese children and adolescents . | OBJECTIVE To evaluate the feasibility , acceptability , and efficacy of an after-school team sports program for reducing weight gain in low-income overweight children . DESIGN Six-month , 2-arm , parallel-group , pilot r and omized controlled trial . SETTING Low-income , racial/ethnic minority community . PARTICIPANTS Twenty-one children in grade s 4 and 5 with a body mass index at or above the 85th percentile . INTERVENTIONS The treatment intervention consisted of an after-school soccer program . The " active placebo " control intervention consisted of an after-school health education program . MAIN OUTCOME MEASURES Implementation , acceptability , body mass index , physical activity measured using accelerometers , reported television and other screen time , self-esteem , depressive symptoms , and weight concerns . RESULTS All 21 children completed the study . Compared with children receiving health education , children in the soccer group had significant decreases in body mass index z scores at 3 and 6 months and significant increases in total daily , moderate , and vigorous physical activity at 3 months . CONCLUSION An after-school team soccer program for overweight children can be a feasible , acceptable , and efficacious intervention for weight control The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown . We examined the effects of aerobic exercise ( AE ) versus resistance exercise ( RE ) without caloric restriction on abdominal adiposity , ectopic fat , and insulin sensitivity and secretion in youth . Forty-five obese adolescent boys were r and omly assigned to one of three 3-month interventions : AE , RE , or a nonexercising control . Abdominal fat was assessed by magnetic resonance imaging , and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy . Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp . Both AE and RE prevented the significant weight gain that was observed in controls . Compared with controls , significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups . Compared with controls , a significant improvement in insulin sensitivity ( 27 % ) was observed in the RE group . Collapsed across groups , changes in visceral fat were associated with changes in intrahepatic lipid ( r = 0.72 ) and insulin sensitivity ( r = −0.47 ) . Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys . RE but not AE is also associated with significant improvements in insulin sensitivity Background / aim Resistance training is an exercise modality at which overweight and obese adolescents can excel and which can therefore positively affect their psychological well-being . The aim of this study was to determine the effect of a 6-month resistance training intervention on the self-concept strength and body composition of overweight and obese adolescent males . Methods 56 overweight and obese males aged 13–17 years were r and omly allocated to an Intervention ( n=30 ) or Control ( n=26 ) group . Primary ( psychological ) and secondary ( strength and body composition ) outcomes were assessed at baseline as well as at 3 ( halfway through the intervention ) , 6 ( immediately postintervention ) and 12 months follow-up . R and om effects mixed modelling was used to determine the effects of the intervention . Results Statistically significant differences between the Intervention and Control groups were observed at 3-month and 6-month assessment s for exercise self-efficacy , resistance training confidence and self-esteem . Large increases in strength for the Intervention group , relative to Controls , were also observed with no substantial changes in body composition shown for either group . Values for all variables returned to baseline following completion of the programme . Conclusions A 6-month resistance training intervention can positively affect the self-concept and strength of overweight and obese adolescent boys BACKGROUND Sedentary activities such as video gaming are independently associated with obesity . Active video games , in which players physically interact with images on screen , may help increase physical activity and improve body composition . OBJECTIVE The aim of this study was to evaluate the effect of active video games over a 6-mo period on weight , body composition , physical activity , and physical fitness . DESIGN We conducted a 2-arm , parallel , r and omized controlled trial in Auckl and , New Zeal and . A total of 322 overweight and obese children aged 10 - 14 y , who were current users of sedentary video games , were r and omly assigned at a 1:1 ratio to receive either an active video game up grade package ( intervention , n = 160 ) or to have no change ( control group , n = 162 ) . The primary outcome was the change from baseline in body mass index ( BMI ; in kg/m(2 ) ) . Secondary outcomes were changes in percentage body fat , physical activity , cardiorespiratory fitness , video game play , and food snacking . RESULTS At 24 wk , the treatment effect on BMI ( -0.24 ; 95 % CI : -0.44 , -0.05 ; P = 0.02 ) favored the intervention group . The change ( ±SE ) in BMI from baseline increased in the control group ( 0.34 ± 0.08 ) but remained the same in the intervention group ( 0.09 ± 0.08 ) . There was also evidence of a reduction in body fat in the intervention group ( -0.83 % ; 95 % CI : -1.54 % , -0.12 % ; P = 0.02 ) . The change in daily time spent playing active video games at 24 wk increased ( 10.03 min ; 95 % CI : 6.26 , 13.81 min ; P < 0.0001 ) with the intervention accompanied by a reduction in the change in daily time spent playing nonactive video games ( -9.39 min ; 95 % CI : -19.38 , 0.59 min ; P = 0.06 ) . CONCLUSION An active video game intervention has a small but definite effect on BMI and body composition in overweight and obese children . This trial was registered in the Australian New Zeal and Clinical Trials Registry at http://www.anzctr.org.au/ as ACTRN12607000632493 OBJECTIVES The primary goals of this study were to determine the effects of a physical activity intervention on the set-shifting aspect of executive function and to explore the potential mechanistic role of cardiac autonomic control , as assessed by heart rate variability ( HRV ) , in the relationship between physical activity and executive function in obese young adolescents . METHOD Obese young adolescents were r and omized either to participate in a physical activity program ( n = 25 ) or to serve as the wait-list control ( n = 25 ) for a 3-month intervention . Outcome measures included physical fitness , obesity status , executive function , and HRV ; these measures were assessed at baseline and within 1 week of the conclusion of the intervention . RESULTS The physical activity program improved the participants ' physical fitness and obesity status . The program also improved executive function-related set-shifting performance , as measured by the total number of errors , and increased the HRV indices of normalized low frequency ( nLF ) and normalized high frequency ( nHF ) . A positive correlation between the nHF time changes and the total number of errors was also observed . CONCLUSION These findings suggest that 3 months of a physical activity intervention effectively increase physical fitness and improve the set-shifting aspect of executive function in obese young adolescents . Furthermore , the physical activity-related alterations in cardiac autonomic control , particularly the parasympathetic response , may be associated with enhanced executive function . ( PsycINFO Data base BACKGROUND Structured exergaming with prescribed moderate intensity physical activity has reduced adiposity among adolescents . The extent to which adolescents reduce adiposity when allowed to self-select intensity level is not known . OBJECTIVE The objective of the study was to examine the influence of exergaming on adolescent girls ' body composition and cardiovascular risk factors . METHODS This r and omized controlled trial assigned 41 overweight and obese girls aged 14 to 18 years to group-based dance exergaming ( 36 h over 3 months ) or to a self-directed care control condition . Body size and composition were measured by anthropometry , dual-energy X-ray absorptiometry [ % fat and bone mineral density { BMD } ] and magnetic resonance imaging . Cardiovascular risk factors included blood pressure , cholesterol , triglycerides , glucose and insulin . RESULTS Attrition was 5 % . Using analysis of covariance controlling for baseline value , age and race , there were no significant condition differences . Per protocol ( attended > 75 % ) , the intervention group significantly decreased abdominal subcutaneous adiposity and increased trunk and spine BMD ( ps < 0.05 ) . Per protocol ( > 2600 steps/session ) , the intervention group significantly decreased leg % fat and decreased abdominal subcutaneous and total adiposity ( ps < 0.05 ) . CONCLUSION Exergaming reduced body fat and increased BMD among those adolescent girls who adhered . Further research is required before exergaming is recommended in clinical setting AIM To determine whether five months of guided active play in overweight or obese children and adolescents under multi-disciplinary management for weight reduction leads to increased physical activity levels in leisure time , as well as changes in aerobic fitness and body composition . METHODS Sixty overweight or obese children and adolescents were r and omly assigned to an intervention or control group . All participants received dietary advice and were encouraged to increase physical activity level . The intervention group additionally participated in 60-minute guided active play/physical activity twice a week for 5 months . Physical activity was recorded ; aerobic fitness and body composition were measured at inclusion and after cessation of intervention . RESULTS Physical activity level during weekend days was significantly higher for the intervention group compared with the controls after 5 months intervention ( p=0.04 ) . The mean reduction in percentage of body fat was 1.8 % ( 95%CI : 0.6 , 3.1 ) in the intervention group ( p=0.04 ) and not significant among the controls ( 0.9 [ -0.9 , 2.7 ] ) . There was no change in aerobic fitness . CONCLUSION Five months of guided active play was associated with increased physical activity levels during weekend days and reduced body fat , although weakly , in overweight and obese children and adolescents participating in multi-disciplinary weight reduction programmes Adjustments for making multiple comparisons in large bodies of data are recommended to avoid rejecting the null hypothesis too readily . Unfortunately , reducing the type I error for null associations increases the type II error for those associations that are not null . The theoretical basis for advocating a routine adjustment for multiple comparisons is the “ universal null hypothesis ” that “ chance ” serves as the first-order explanation for observed phenomena . This hypothesis undermines the basic premises of empirical research , which holds that nature hollows regular laws that may he studied through observations . A policy of not making adjustments for multiple comparisons is preferable because it will lead to fewer errors of interpretation when the data under evaluation are not r and om numbers but actual observations on nature . Furthermore , scientists should not he so reluctant to explore leads that may turn out to he wrong that they penalize themselves by missing possibly important findings PURPOSE We assessed the exercise tolerance and cardiorespiratory responses during 2-month weight-loss programmes using the 6-minute walking test ( 6MWT ) in obese children . METHODS Twenty-eight male obese children were r and omly assigned to either a control group ( C ) , an energy restriction group ( R ) , an exercise training at maximum lipid-oxidation ( LIPOXmax ) group ( E ) , or an energy restriction/training group ( RE ) . The body composition , the submaximal incremental cycling exercise , and the 6MWT were performed before and after the 2-month programme . RESULTS . After the programme , RE group showed a significant improvement of body composition ( body weight reduced by 6.3 ± 1.5 kg , p < 0.01 ) , and an increase of 6-minute walking distance ( 6MWD ) ( + 13.7 % , p < 0.01 ) . Similarly , maximum oxygen uptake calculated according to the American College of Science Medicine guideline ( VO(2max ) ACSM ) and VO(2max ) predicted from 6MWD were respectively higher ( + 12.9 % and + 10.0 % , p < 0.01 ) than the R or E groups . Bl and -Altman analysis highlighted an agreement of these two methods of VO(2max ) measurement . Moreover , in all participants the 6MWD was significantly correlated with VO(2max ) ACSM and LIPOXmax ( r = 0.77 , p < 0.001 and r = 0.67 , p < 0.01 ; respectively ) before the programme as well as their changes in percentage over the programme ( r = 0.85 and r = 0.86 , p < 0.0001 ; respectively ) . CONCLUSIONS We concluded that a 2-month weight-loss programme including energy restriction and exercise training targeted at LIPOXmax improved body composition and cardiorespiratory tolerance in obese children . Furthermore , the 6MWT could be considered as a useful and reliable tool for the assessment and the follow-up of cardiorespiratory responses during weight-loss programme in obese children OBJECTIVES We sought to characterize the impact of obesity on vascular function in adolescents and to determine whether an exercise program reverses abnormalities in endothelial function . BACKGROUND Obesity , a major modifiable risk factor for cardiovascular disease , is epidemic in Western societies , with rapid rates of increase in the young . Atherosclerosis begins in childhood , and endothelial dysfunction is its earliest detectable manifestation . METHODS The influence of eight weeks of circuit training ( CT ) was examined in 19 obese subjects ( 14.3 + /- 1.5 years ) , using a r and omized , crossover protocol . Functional capacity and muscular strength were assessed by st and ard techniques . Body composition was examined using anthropometric measures and dual-energy X-ray absorptiometry . Conduit vessel endothelial function was assessed using high-resolution ultrasound and flow-mediated dilation ( FMD ) of the brachial artery . RESULTS Circuit training decreased abdominal and trunk fat and significantly improved fitness and muscular strength ( p < 0.05 ) . In the obese group , FMD was significantly impaired relative to control subjects ( n = 20 ) at entry ( 5.3 + /- 0.9 % vs. 8.9 + /- 1.5 % , p < 0.05 ) and was normalized after CT ( 8.8 + /- 0.8 % , p < 0.05 ) . CONCLUSIONS Circuit training improved functional capacity , muscular strength , and body composition in obese adolescents . Furthermore , conduit vessel function was normalized after exercise training . If vascular dysfunction is an integral component of the pathogenesis of vascular disease , this study supports the value of an exercise program in the management of obese adolescents OBJECTIVES The aim of this study was to determine the effects of physical activity on systemic blood pressure ( BP ) and early markers of atherosclerosis in pre-pubertal obese children . BACKGROUND Hypertension and endothelial dysfunction are premature complications of obesity . METHODS We performed a 3-month r and omized controlled trial with a modified crossover design : 44 pre-pubertal obese children ( age 8.9 + or - 1.5 years ) were r and omly assigned ( 1:1 ) to an exercise ( n = 22 ) or a control group ( n = 22 ) . We recruited 22 lean children ( age 8.5 + or - 1.5 years ) for baseline comparison . The exercise group trained 60 min 3 times/week during 3 months , whereas control subjects remained relatively inactive . Then , both groups trained twice/week during 3 months . We assessed changes at 3 and 6 months in office and 24-h BP , arterial intima-media thickness ( IMT ) and stiffness , endothelial function ( flow-mediated dilation ) , body mass index ( BMI ) , body fat , cardiorespiratory fitness ( maximal oxygen consumption [ VO(2)max ] ) , physical activity , and biological markers . RESULTS Obese children had higher BP , arterial stiffness , body weight , BMI , abdominal fat , insulin resistance indexes , and C-reactive protein levels , and lower flow-mediated dilation , VO(2)max , physical activity , and high-density lipoprotein cholesterol levels than lean subjects . At 3 months , we observed significant changes in 24-h systolic BP ( exercise -6.9 + or - 13.5 mm Hg vs. control 3.8 + or - 7.9 mm Hg , -0.8 + or - 1.5 st and ard deviation score [ SDS ] vs. 0.4 + or - 0.8 SDS ) , diastolic BP ( -0.5 + or - 1.0 SDS vs. 0 + or - 1.4 SDS ) , hypertension rate ( -12 % vs. -1 % ) , office BP , BMI z-score , abdominal fat , and VO(2)max . At 6 months , change differences in arterial stiffness and IMT were significant . CONCLUSIONS A regular physical activity program reduces BP , arterial stiffness , and abdominal fat ; increases cardiorespiratory fitness ; and delays arterial wall remodeling in pre-pubertal obese children . ( Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children : A R and omized Controlled Trial ; NCT00801645 ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES To determine whether a large-scale physical activity intervention could affect body composition in primary school students in Beijing , China . METHODS The study design was one-year cluster r and omized controlled trial of physical activity intervention ( 20 min of daily exercise in the classroom ) with an additional year of follow-up among 4 700 students aged 8 - 11 years at baseline . RESULTS After the one-year intervention , BMI increased by 0.56 kg/m(2 ) ( SD 1.15 ) in the intervention group and by 0.72 kg/m(2 ) ( SD 1.20 ) in the control group , with a mean difference of -0.15 kg/m(2 ) ( 95 % CI : -0.28 to -0.02 ) . BMI z score decreased by -0.05 ( SD 0.44 ) in the intervention group , but increased by 0.01 ( SD 0.46 ) in the control group , with a mean difference of -0.07 ( -0.13 to -0.01 ) . After another year of follow up , compared to the control group , children in the intervention group had significantly lower BMI ( -0.13 , -0.25 to -0.01 ) , BMI z score ( -0.05 , -0.10 to -0.01 ) , fat mass ( -0.27 kg , -0.53 to -0.02 ) and percent body fat ( -0.53 , -1.00 to -0.05 ) . The intervention had a more pronounced effect on weight , height , BMI , BMI z score , and body composition among obese children than among normal weight or overweight children . Compared to the control group , the intervention group had a significantly higher percentage of children who maintained or reduced their BMI z score at year 1 ( P=0.008 ) and year 2 ( P=0.04 ) . CONCLUSIONS These findings suggest that 20 min of daily moderate to vigorous physical activity during the school year is a feasible and effective way to prevent excessive gain of body weight , BMI , and body fatness in primary school students It is unclear whether regular exercise alone ( no caloric restriction ) is a useful strategy to reduce adiposity and obesity-related metabolic risk factors in obese girls . We examined the effects of aerobic ( AE ) vs. resistance exercise ( RE ) alone on visceral adipose tissue ( VAT ) , intrahepatic lipid , and insulin sensitivity in obese girls . Forty-four obese adolescent girls ( BMI ≥95th percentile , 12 - 18 yr ) with abdominal obesity ( waist circumference 106.5 ± 11.1 cm ) were r and omized to 3 mo of 180 min/wk AE ( n = 16 ) or RE ( n = 16 ) or a nonexercising control group ( n = 12 ) . Total fat and VAT were assessed by MRI and intrahepatic lipid by proton magnetic resonance spectroscopy . Intermuscular AT ( IMAT ) was measured by CT . Insulin sensitivity was evaluated by a 3-h hyperinsulinemic ( 80 mU·m(2)·min(-1 ) ) euglycemic clamp . Compared with controls ( 0.13 ± 1.10 kg ) , body weight did not change ( P > 0.1 ) in the AE ( -1.31 ± 1.43 kg ) and RE ( -0.31 ± 1.38 kg ) groups . Despite the absence of weight loss , total body fat ( % ) and IMAT decreased ( P < 0.05 ) in both exercise groups compared with control . Compared with control , significant ( P < 0.05 ) reductions in VAT ( Δ-15.68 ± 7.64 cm(2 ) ) and intrahepatic lipid ( Δ-1.70 ± 0.74 % ) and improvement in insulin sensitivity ( Δ0.92 ± 0.27 mg·kg(-1)·min(-1 ) per μU/ml ) were observed in the AE group but not the RE group . Improvements in insulin sensitivity in the AE group were associated with the reductions in total AT mass ( r = -0.65 , P = 0.02 ) . In obese adolescent girls , AE but not RE is effective in reducing liver fat and visceral adiposity and improving insulin sensitivity independent of weight loss or calorie restriction Background Early obesity and its transfer to the adulthood , increases likelihood incidence of coronary artery disease ( CAD ) . ATP-binding cassette transporter ( ABCA1 ) as a member of the ABC transporters family plays a crucial role in reverse cholesterol transport and CAD prevention . Objective The current study aim ed to investigate ABCA1 expression in lymphocytes , plasma apolipoprotein A-I and HDL-C in response to eight-week interval endurance rope training in overweight and obese boy adolescents . Patients and Methods Thirty students ( 17.3 ± 1.1 yr , 85.73 ± 11.68 kg and 28.41 ± 2.36 kg / m² ) volunteered and were r and omly assigned into training ( n= 15 ) and control ( n = 15 ) groups . Exercise protocol was interval endurance rope training ( 8 wk , 4 d/wk and 40 min/d ) . Cell hemolysis and sensitive Elisa method was used for Lymphocyte ABAC1 protein expression.t-test was employed . Results The independent- sample s T-Test results showed that after 8 weeks IERT , the levels of lymphocyte ABCA1 expression ( P = 0/001 ) and VO2max(P = 0/001 ) significantly increased and plasma levels of TG ( P = 0.017 ) , TC ( P = 0.001 ) , LDL-c/HDL-c ( P = 0.026),TC/HDL-c ( P = 0.002 ) and measures of BF% ( P = 0/015 ) and BMI ( P = 0.042 ) as anthropometric indicators significantly decreased . Changes of other variables such as increase in ApoA-I , HDL-c and decrease in LDL-c , body weight , were not significant . Conclusions The findings of this study proved that eight-week interval endurance rope training can have positive effects on lymphocyte ABCA1 protein expression ( as gatekeeper of reverse cholesterol process ) and lipid profiles among overweight and obese boy adolescents Objective To find the optimal exercise program to be recommended in reducing adiposity and promoting long-term physical activity adherence in a sample of overweight adolescents . Methods Forty-five overweight adolescents were r and omly divided into three exercise groups , to perform two phases of physical activity as follows : in the first phase , the first group performed a 16-week moderate-intensity resistance training ( RT ) , the second group performed a 16-week high-intensity RT , and the third group performed a 16-week aerobic training ( AT ) ; in the second phase , all groups performed a 6-week AT . Anthropometric body composition and fitness measures were considered as outcome measures . Results After the second protocol , both RT groups showed a significant improvement in percentage of fat mass ( F2,76 = 5.843 ; p = 0.004 ; h2 = 0.133 ) and free fat mass ( F2,76 = 6.254 ; p = 0.003 ; h2 = 0.141 ) , and in fitness tests ( p < 0.01 ) . The VO2max values of the RT groups were significantly higher than those of the AT group ( F2,38 = 4.264 ; p = 0.021 ; h2 = 0.183 ) . The rate of adherence to exercise was an average of 94 % in both RT groups , whereas in the AT group , it was 83 % . During the 12-week post-intervention follow-up , the number of participants who continued to perform physical activities was significantly higher in both the RT groups than in the AT group ( p < 0.05 ) . Conclusion The present study provides preliminary evidence that moderate-to-intense RT , followed by AT , can be an effective treatment for overweight adolescents , and the positive effects are maintained even after 12 weeks of follow-up CONTEXT Pediatric studies have shown that aerobic exercise reduces metabolic risk , but dose-response information is not available . OBJECTIVES To test the effect of different doses of aerobic training on insulin resistance , fatness , visceral fat , and fitness in overweight , sedentary children and to test moderation by sex and race . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled efficacy trial conducted from 2003 through 2007 in which 222 overweight or obese sedentary children ( mean age , 9.4 years ; 42 % male ; 58 % black ) were recruited from 15 public schools in the Augusta , Georgia , area . INTERVENTION Children were r and omly assigned to low-dose ( 20 min/d ; n = 71 ) or high-dose ( 40 min/d ; n = 73 ) aerobic training ( 5 d/wk ; mean duration , 13 [ SD , 1.6 ] weeks ) or a control condition ( usual physical activity ; n = 78 ) . MAIN OUTCOME MEASURES The prespecified primary outcomes were postintervention type 2 diabetes risk assessed by insulin area under the curve ( AUC ) from an oral glucose tolerance test , aerobic fitness ( peak oxygen consumption [ VO2 ] ) , percent body fat via dual-energy x-ray absorptiometry , and visceral fat via magnetic resonance , analyzed by intention to treat . RESULTS The study had 94 % retention ( n = 209 ) . Most children ( 85 % ) were obese . At baseline , mean body mass index was 26 ( SD , 4.4 ) . Reductions in insulin AUC were larger in the high-dose group ( adjusted mean difference , -3.56 [ 95 % CI , -6.26 to -0.85 ] × 10(3 ) μU/mL ; P = .01 ) and the low-dose group ( adjusted mean difference , -2.96 [ 95 % CI , -5.69 to -0.22 ] × 10(3 ) μU/mL ; P = .03 ) than the control group . Dose-response trends were also observed for body fat ( adjusted mean difference , -1.4 % [ 95 % CI , -2.2 % to -0.7 % ] ; P < .001 and -0.8 % [ 95 % CI , -1.6 % to -0.07 % ] ; P = .03 ) and visceral fat ( adjusted mean difference , -3.9 cm3 [ 95 % CI , -6.0 to -1.7 cm3 ] ; P < .001 and -2.8 cm3 [ 95 % CI , -4.9 to -0.6 cm3 ] ; P = .01 ) in the high- and low-dose vs control groups , respectively . Effects in the high- and low-dose groups vs control were similar for fitness ( adjusted mean difference in peak VO2 , 2.4 [ 95 % CI , 0.4 - 4.5 ] mL/kg/min ; P = .02 and 2.4 [ 95 % CI , 0.3 - 4.5 ] mL/kg/min ; P = .03 , respectively ) . High- vs low-dose group effects were similar for these outcomes . There was no moderation by sex or race . CONCLUSION In this trial , after 13 weeks , 20 or 40 min/d of aerobic training improved fitness and demonstrated dose-response benefits for insulin resistance and general and visceral adiposity in sedentary overweight or obese children , regardless of sex or race . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00108901 INTRODUCTION Developing effective exercise programmes for the paediatric population is a strategy for decreasing obesity and is expected to help in eventually limiting obesity-associated long-term health and societal impact . In this study , the effects of a 12-week twice weekly additional exercise training , which comprised a combination of circuit-based resistance training and aerobic exercises , in additional to typical physical education sessions , on aerobic fitness , body composition and serum C-reactive protein ( CRP ) and lipids were analysed in 13- to 14-year-old obese boys contrasted with a control group . MATERIAL S AND METHODS Both the exercise group ( EG , n = 12 ) and control group ( CG , n = 12 ) participated in the typical 2 sessions of 40-minute physical education ( PE ) per week in schools , but only EG participated in additional 2 sessions per week of 45 to 60 minutes per session of exercise training , which comprised a combination of circuit-based resistance training and aerobic exercises maintained at 65 % to 85 % maximum heart rate ( HRmax = 220 - age ) . Body composition was measured using dual energy X-ray absorptiometry ( DEXA ) . Fasting serum CRP and blood lipids were analysed pre- and postexercise programme . Aerobic fitness was measured by an objective laboratory submaximal exercise test , PWC170 ( Predicted Work Capacity at HR 170 bpm ) . RESULTS Exercise training significantly improved lean muscle mass , body mass index , fitness , resting HR , systolic blood pressure and triglycerides in EG . Serum CRP concentrations were elevated at baseline in both groups , but training did not result in a change in CRP levels . In the CG , body weight increased significantly at the end of the 12-week period . CONCLUSION This study supports the value of an additional exercise training programme , beyond the typical twice weekly physical education classes , to produce physiological benefits in the management of obesity in adolescents , including prevention of weight gain This prospect i ve , r and omized study investigated the effect of exercise on leptin , insulin , cortisol and lipid profiles in obese children . A total of 40 obese boys aged 10 - 12 years with a body mass index ( BMI ) ≥ 30 kg/m2 were r and omly separated into an exercise group ( n = 20 ) that underwent a 12-week aerobic exercise programme and a non-exercise ( control ) group ( n = 20 ) . The BMI , low-density lipoprotein , cortisol , leptin and insulin levels were significantly lower in the exercise group after 12 weeks compared with baseline values , whereas high-density lipoprotein levels were significantly higher . In contrast , in the control group , low-density lipoprotein , cortisol and leptin levels were significantly higher after 12 weeks compared with baseline values while high-density lipoprotein levels were significantly lower . These findings indicate the importance of regular exercise in the regulation of body weight and protection against cardiovascular risk factors in obese children Given the increase in obesity in developed and developing countries and its concomitant morbidity , successful treatment approaches are needed . We examined the effect of a structured exercise intervention in overweight children in a slum in Recife , Pernambuco State , Brazil . This was a r and omized , controlled efficacy trial . Seventy-eight children were r and omized . Exercise was supervised , consisting of three 50 ' group aerobics sessions per week for six months . All participants maintained ad libitum diets . Based on intention-to-treat analyses , children in both groups had a significant increase in weight at follow-up ( p-value for within-group increase < or = 0.01 ) . The increase in weight was significantly lower in the exercise group ( mean difference between groups ; -1.37 ; 95%CI : -2.00 ; -0.74 ) . A significant difference ( p = 0.049 ) between the exercise and control groups at six-month follow-up was also found for BMI ( mean difference between groups ; -0.53 ; 95%CI : -1.06 ; -0.002 ) . When we restricted the analyses to children who completed the trial ( intervention = 30 and control = 38 ) , the results were the same . An exercise program for children , sustained for six months , was effective for reducing weight gain in overweight children living in a very poor neighborhood Abstract This study examined the effects of a 6-week intermittent exercise training , at different intensities , on body composition , functional walking and aerobic endurance in overweight children . Forty-eight overweight children ( age : 10.4 ± 0.9 years ) were r and omly assigned to either intervention or control group . Lower and higher intensity intermittent exercise groups ( LIIE and HIIE ) performed intermittent running three times a week . LIIE performed more intervals at a lower intensity [ 16 intervals at 100 % of individual maximal aerobic speed ( MAS ) , 8 minutes in total ] , and HIIE performed fewer intervals at a higher intensity ( 12 intervals at 120 % of MAS , 6 minutes in total ) . Each interval consisted of a 15-second run at the required speed , followed by a 15-second passive recovery . After 6 weeks , HIIE had a significantly ( p < 0.05 ) higher percentage reduction in sum of skinfolds ( i.e. calf and triceps ) , and significantly ( p < 0.05 ) fewer steps during the functional obstacle performance , as compared with LIIE and control group . Significant improvement ( p < 0.05 ) was found in intermittent aerobic endurance for HIIE as compared to the control group . Higher intensity intermittent training is an effective and time-efficient intervention for improving body composition , functional walking and aerobic endurance in overweight children PURPOSE Children with high levels of total body fat mass ( TFM ) and visceral adipose tissue ( VAT ) have elevated levels of certain risk factors for coronary artery disease and non-insulin-dependent diabetes mellitus . We tested the hypothesis that controlled physical training , without dietary intervention , would have a favorable impact on VAT and percent body fat ( % BF ) in obese children . METHODS A volunteer sample of 74 obese children , 7 - 11 yr of age , accepted r and om assignment to physical training or control groups . Before and after 4 months of intervention , measurements were obtained for VAT , TFM , % BF , daily physical activity , and cardiovascular fitness . The intervention involved 4 months of controlled physical training 5 d x wk(-1 ) , 40 min per session , at a mean heart rate ( HR ) of 157 beats x min(-1 ) . The estimated energy expenditure ( EE ) per training session was 925+/-201 kJ. RESULTS Compared with the control group , the physical training group declined significantly in % BF ( delta = -2.2 % ) ( P < 0.01 ) , TFM ( delta = -3.1 % ) ( P < 0.01 ) , and subcutaneous abdominal adipose tissue ( delta = - 16.1 % ) ( P < 0.05 ) , and increased significantly in fat-free mass ( delta = + 6.1 % ) ( P < 0.05 ) and moderate-to-very hard physical activity ( delta = + 14.1 % ) ( P < 0.05 ) . The increase in VAT was significantly less in the physical training group ( delta = + 0.5 % ) as compared with that in the control group ( delta = + 8.1 % ) ( P < 0.05 ) . CONCLUSIONS This study showed that during physical training obese children : 1 ) were capable of participating in a substantial amount of high intensity physical training over a 4-month period : 2 ) accumulated significantly less VAT as compared with nonexercising controls ; and 3 ) experienced other beneficial changes in total and regional body composition OBJECTIVE The beat-to-beat variability in electrocardiogram intervals ( RR , i.e. , heart-period variability ) provides information on cardiac autonomic activity that predicts arrhythmias and mortality rate in animals and adults . We determined the effect of physical training on heart-period variability in obese children . METHODS Thirty-five subjects were r and omly assigned to physical training and control groups . The training involved 4 months of exercise , 5 days per week , 40 minutes per day . Cardiovascular fitness was measured with submaximal heart rate during supine cycling ; percentage of body fat was measured with dual-energy absorptiometry ; and resting heart-period variability parameters were measured in a supine position . A pretraining to posttraining change score was computed for each variable . The effect of the training was determined by comparing the changes of the training and control groups . RESULTS Compared with the control group , the trained group ( 1 ) reduced submaximal heart rate and percentage of body fat ( p < 0.01 ) ; ( 2 ) increased in the root mean square of successive differences , a time-domain parameter reflective of vagal tone ( p < 0.05 ) ; ( 3 ) decreased in low-frequency power expressed as a percentage of total power , a frequency-domain index of combined sympathetic and vagal activity ( p < 0.03 ) ; and ( 4 ) decreased in the ratio of low- to high-frequency power , an index of sympathetic-parasympathetic balance ( p < 0.01 ) . CONCLUSIONS In obese children , physical training alters cardiac autonomic function favorably by reducing the ratio of sympathetic to parasympathetic activity OBJECTIVES The present study aim ed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation ( FMD ) carotid intima-media thickness ( IMT ) and cardiovascular risk factors ( RF ) . BACKGROUND Childhood obesity contributes to adult obesity and subsequent cardiovascular disease . Physical inactivity is a major RF for obesity , endothelial dysfunction , and elevated carotid IMT , culminating in early atherosclerotic disease . METHODS Sixty-seven obese subjects ( age 14.7 + /- 2.2 years ) were r and omly assigned to 6 months ' exercise or non-exercise protocol . We examined the influence of exercises ( 1 h , 3 times/week ) on FMD , IMT , and cardiovascular risk profile . RESULTS Compared with lean control subjects , obese children demonstrated at baseline significantly impaired FMD ( 4.09 + /- 1.76 % vs. 10.65 + /- 1.95 % , p < 0.001 ) , increased IMT ( 0.48 + /- 0.08 mm vs. 0.37 + /- 0.05 mm , p < 0.001 ) , and a number of obesity-related cardiovascular RF . Significant improvements were observed in the exercise group for IMT ( 0.44 + /- 0.08 mm , p = 0.012 , -6.3 % ) and FMD ( 7.71 + /- 2.53 % , p < 0.001 , + 127 % ) . This improvement correlated with reduced RF , such as body mass index st and ard deviation scores , body fat mass , waist/hip ratio , ambulatory systolic blood pressure , fasting insulin , triglycerides , low-density lipoprotein/high-density lipoprotein ratio , and low-degree inflammation ( C-reactive protein , fibrinogen ) . CONCLUSIONS The present study documented increased IMT , impaired endothelial function , and various elevated cardiovascular RF in young obese subjects . Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children The purpose of this study was to apply the lactate threshold concept to develop a more evidence -informed exercise program for obese children . 60 obese children ( 26 girls and 34 boys , age : 9 - 10 years , BMI : 25.4 + /- 2.2kg/m(2 ) ) were recruited and half of them were r and omly selected to be trained for eight weeks with a controlled exercise intensity at lactate threshold . The trained children achieved significant improvements on their body composition and functional capacity compared with the control group . The findings suggested that the training program with intensity at lactate threshold is effective and safe for 9 - 10 year old children with obesity OBJECTIVES Atherosclerosis is a disease that begins in childhood ; endothelial dysfunction is its earliest detectable manifestation , and primary prevention strategies are likely to be most effective if instituted early . The aim of this study was to characterize the impact of obesity on vascular function in young children and to determine whether an exercise program improves abnormalities in vascular function . STUDY DESIGN The influence of 8 weeks of exercise training was examined in 14 obese subjects , 8.9 + /- 0.4 years of age , with the use of a r and omized crossover protocol . Conduit vessel endothelial function was assessed by means of high-resolution ultrasound and flow-mediated dilation of the brachial artery ( FMD ) . RESULTS Exercise training did not change subcutaneous fat mass , body weight , or body mass index . FMD in the obese group was significantly impaired relative to matched control subjects at entry ( 6.00 % + /- 0.69 % to 12.32 % + /- 3.14 % , P < .0001 ) . FMD significantly improved with exercise training ( 7.35 % + /- 0.99 % , P < .05 ) in the obese group . CONCLUSIONS Conduit vessel FMD , a vali date d surrogate measure of early atherosclerosis , was impaired in obese children but improved as a result of exercise training . This study supports the value of an exercise program in the treatment of obese children in a primary prevention setting Background : The chronic effects of high-intensity endurance training on metabolic health outcomes in overweight adolescents remains poorly understood . Objective : To test the hypothesis that high-intensity endurance training ( ET ) is superior to moderate-intensity ET for improving risk factors for type 2 diabetes in overweight adolescents . Design and methods : In this r and omized trial , 106 overweight and obese adolescents ( 15.2 years ; 76 % female ; 62 % Caucasian ) were r and omly assigned to high-intensity ET ( 70–85 % of heart rate reserve , n=38 ) , moderate-intensity ET ( 40–55 % heart rate reserve ; n=32 ) or control for 6 months ( n=36 ) . The primary and secondary outcome measures were insulin sensitivity assessed using a frequently sample d intravenous glucose tolerance test and hepatic triglyceride content with magnetic resonance spectroscopy . Exploratory outcomes were cardiorespiratory fitness , physical activity and MRI and dual x-ray absorptiometry-derived measures of adiposity . Results : The study had 96 % retention and attendance was 61±21 % and 55±24 % in the high- and moderate-intensity ET arms . Intention-to-treat analyses revealed that , at follow-up , insulin sensitivity was not different between high-intensity ( −1.0 mU kg−1 min−1 ; 95 % confidence interval ( CI ) : −1.6 , + 1.4 mU kg−1 min−1 ) and moderate-intensity ( + 0.26 mU kg−1 min−1 ; 95 % CI : −1.3 , + 1.8 mU kg−1 min−1 ) ET arms compared with controls ( interaction , P=0.97 ) . Similarly , hepatic triglyceride at follow-up was not different in high-intensity ( −1.7 % fat/water ( F/W ) ; 95 % CI : −7.0 , + 3.6 % F/W ) and moderate-intensity ( −0.40 % FW ; 95 % CI : −6.0 , + 5.3 % F/W ) ET compared with controls . Both high intensity ( + 4.4 ml per kg-FFM ( fat-free mass ) per minute ; 95 % CI : 1.7 , 7.1 ml kg-FFM−1 min−1 ) and moderate intensity ( + 4.4 ml kg-FFM−1 min−1 ; 95 % CI : 1.6 , 7.3 ml kg-FFM−1 min−1 ) increased cardiorespiratory fitness , relative to controls ( interaction P<0.001 ) . Conclusions : ET improves cardiorespiratory fitness among obese adolescents ; however , owing to lack of compliance , the influence of exercise intensity on insulin sensitivity and hepatic triglycerides remains unclear PURPOSE Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children , such as type 2 diabetes . Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults . However , very little is known regarding the effects of exercise on insulin resistance in youth . Therefore , we examined the effects of a 16-wk resistance training exercise intervention on insulin sensitivity in youth at high risk for developing type 2 diabetes . METHODS Twenty-two overweight Latino adolescent males were r and omly assigned to either a twice-per-week resistance training group ( RT=11 ) or a nonexercising control group ( C=11 ) for 16 wk . Strength was assessed by one-repetition maximum , body composition was quantified by dual-energy x-ray absorptiometry , and insulin sensitivity was determined by the frequently sample d intravenous glucose tolerance test with minimal modeling . RESULTS Significant increases in upper- and lower-body strength were observed in the RT compared with the C group . The RT group significantly increased insulin sensitivity compared with the C group ( P<0.05 ) , and this increase remained significant after adjustment for changes in total fat mass and total lean tissue mass ( P<0.05 ) . Compared with baseline values , insulin sensitivity increased 45.1+/-7.3 % in the RT group versus -0.9+/-12.9 % in controls ( P<0.01 ) . CONCLUSION A twice-per-week 16-wk resistance training program can significantly increase insulin sensitivity in overweight Latino adolescent males independent of changes in body composition OBJECTIVE We conducted a study to determine if wearing a pedometer affects weight , body mass index ( BMI ) , or mediators of physical activity among families . METHODS Eighty-seven families were r and omized to 1 of 3 treatments : pedometer plus education ( PE ) , pedometer ( P ) , or control ( C ) . Participants in the PE and P groups wore pedometers and were encouraged to walk 10,000 steps daily for 12 weeks . PE group participants attended 6 sessions on healthy eating and exercise . Participants were surveyed about their knowledge and attitudes about healthy eating and physical activity prior to r and omization , at the end of the intervention , and 9 months later . Their heights and weights were measured and BMI calculated . RESULTS Children 's BMI percentile decreased from baseline to end of intervention ( -0.18 % ) and at 9-month follow-up ( -0.08 % ) but did not differ by treatment . Children 's BMI percentile varied by parental obesity status ( average BMI percentile was 88.7 % for children of obese parents and 78.5 % for children of non-obese parents ) . Parents ' weight decreased slightly by intervention 's end ( 0.6 pounds ) and at 9 months ( 1.2 pounds ) , but change was similar among groups . Attitudes about their physical activity level relative to their peers improved significantly among children and parents wearing the pedometer . Self-efficacy improved for parents wearing the pedometer . Both children and parents felt the pedometer increased their activity level , but most were unlikely to wear it beyond the intervention . CONCLUSIONS The pedometer had little impact on the activity level , weight , or BMI of participants BACKGROUND The prevalence of overweight and obesity in Chinese children and adolescents was increasing during the past few decades . The goal of this study was to investigate the effects of after-school exercise with or without diet restriction on total and central obesity , fitness level , and metabolic profile in overweight Chinese adolescents . METHODS A ten-week weight loss trial was performed using a 2 × 2 block design ( exercise × diet ) . Ninety-three overweight adolescents ( average age : ( 13.6 ± 0.7 ) years ; body mass index ( BMI ): 22.4 - 34.1 kg/m(2 ) ) were r and omly assigned to four groups : 1 ) diet ( D ) ; 2 ) exercise ( EX ) ; 3 ) diet plus exercise ( DEX ) ; and 4 ) overweight control ( C ) . Caloric intake recipes were enacted based on individual age and corresponding ideal body weight . One-hour after-school exercise was performed once per day , four days per week for ten weeks . Changes of anthropometry , body composition , aerobic fitness , and metabolic biomarkers were determined . RESULTS Groups D , EX and DEX had a significant decrease in BMI ( P < 0.01 ) after the intervention . The percentage of body and truncal fat , and waist circumference were independently reduced by exercise ( P < 0.05 and P < 0.01 ) , but not diet . The decrease in body fat percentage was positively related with the exercise compliance ( r = 0.34 , P = 0.01 ) . Exercise decreased truncal fat percentage and waist circumference , suggesting a reduction of central adiposity , but did not significantly affect body weight and BMI . Exercise significantly reduced serum low-density lipoprotein cholesterol ( P = 0.037 ) , which was positively correlated with decreases of truncal fat percentage ( r = 0.222 , P = 0.048 ) . No significant effects of interventions on insulin sensitivity , early insulin release index , and aerobic fitness were observed . CONCLUSION At least twice a week of one-hour after-school exercise significantly attenuated central adiposity and had a significant impact on lipid profiles in overweight Chinese adolescents OBJECTIVE To determine whether an exercise intervention using an active video game ( Dance Dance Revolution [ DDR ] ) is effective in improving endothelial dysfunction ( EDF ) and other risk factors in overweight children . DESIGN Thirty-five children ( Body mass index > or = 85(th ) percentile , mean age 10.21+/-1.67 years , 17 females ) with EDF were assessed for flow-mediated dilation ( FMD ) , lipids , insulin , glucose , NO(2)+NO(3 ) , asymmetric dimethylarginine , symmetric dimethylarginine , l-arginine , height , weight , aerobic fitness , and blood pressure . In a sub sample , tumor necrosis factor alpha , interleukin-6 , C-reactive protein , and adiponectin were also assessed . Subjects were r and omly assigned to 12-weeks of aerobic exercise ( EX ) using DDR or to a non-exercising delayed-treatment control group ( DTC ) . RESULTS EX had significant improvements in FMD ( 5.56+/-5.04 % compared with 0.263+/-4.54 % , p=0.008 ) , exercise time on the grade d exercise test ( 53.59+/-91.54 compared with -12.83+/-68.10 seconds , p=0.025 ) , mean arterial pressure ( MAP ) ( -5.62+/-7.03 compared with -1.44+/-2.16 mmHg , p=0.05 ) , weight ( 0.91+/-1.53 compared with 2.43+/-1.80 kg , p=0.017 ) and peak VO(2 ) ( 2.38+/-3.91 compared with -1.23+/-3.18 mg/kg/min , p=0.005 ) compared with the DTC . Thirteen EX subjects achieved normal EDF while ten did not . These groups differed at baseline with regard to total cholesterol ( TC ) and low-density lipoprotein ( LDL ) . CONCLUSION Twelve weeks of DDR-use improved FMD , aerobic fitness , and MAP in overweight children . Improvements occurred without changes in inflammatory markers or nitric oxide production . The results document the need to explore relationships between obesity , endothelial function , inflammation , lipids , exercise intensity , and gender in a larger sample of overweight children Abstract The effects of a recreational soccer program ( RSP ) upon body composition , heart rate variability ( HRV ) , biochemical markers , cardio-respiratory fitness , and endothelial function in obese adolescents were investigated . A r and omised controlled clinical trial was conducted with 30 adolescents aged 12–17 years and body mass index ( BMI ) > 2 st and ard deviations of WHO reference values , which were assigned to RSP ( n = 10 , 2 girls ) and obese control ( n = 10 , 4 girls ) groups . The 12-week RSP included 60-min sessions performed 3 times/week . BMI , waist circumference , blood pressure , blood glucose , lipid profile , insulin , C-reactive protein , HRV , and maximal oxygen consumption ( VO2peak ) were evaluated following st and ardised procedures . Body composition was determined by dual-energy X-ray absorptiometry and endothelial function by venous occlusion plethysmography . After intervention , RSP exhibited significant reductions in BMI ( −0.7 ± 0.2 kg · m–2 ) , waist circumference ( −8.2 ± 1.4 cm ) , % body fat ( −2.2 ± 0.4 % ) , systolic blood pressure ( −5.0 ± 2.3 mmHg ) , total cholesterol ( −16.2 ± 5.8 mg · dL−1 ) , triglycerides ( −20.5 ± 12.9 mg · dL−1 ) , C-reactive protein ( −0.06 ± 0.01 mg · dL−1 ) , insulin resistance ( HOMA-IR , −1.4 ± 0.6 ) , and sympathetic activity ( LF , −13.9 ± 6.6 un ) vs. controls ( P < 0.05 ) . Significant increase was observed in parasympathetic activity ( HF , 13.9 ± 6.6 un ) , VO2peak ( 7.9 ± 2.8 ml · kg−1 · min−1 ) , and high-density lipoprotein cholesterol ( 11.0 ± 6.3 mg · dL−1 ) ( P < 0.05 ) . Vascular conductance ( 19.5 ± 8.1 ml · min−1 · 100 ml , P = 0.005 ) increased and vascular resistance ( −5.9 ± 2.4 ml · min−1 · 100 ml , P = 0.041 ) decreased in RSP , but not in controls . A 12-week recreational soccer intervention was effective to improve biochemical , cardiovascular , and fitness health markers in obese adolescents OBJECTIVES To assess sub clinical inflammation , fasting insulin , and endothelial function before and after exercise in overweight children and adolescents . STUDY DESIGN Twenty-five children ( body mass index [ BMI ] > 85th percentile ) were assessed for brachial artery flow-mediated dilation ( FMD ) , nitroglycerin-induced dilation , C-reactive protein ( CRP ) , lipids , glucose , insulin , oral glucose tolerance , body composition , aerobic fitness ( peak oxygen uptake [ VO 2 peak ] ) , and blood pressure . Twenty of these persons were equally and r and omly assigned to either 8 weeks of stationary cycling or to a non-exercising control group . RESULTS A baseline correlation was found between CRP and fasting insulin ( r = 0.62 ; P < .001 ) , which remained significant after adjusting for baseline variables ( r = 0.53 ; P < .05 ) . After 8 weeks , significant improvements were observed in the exercise group compared with the control group for VO 2 peak ( exercise group = 21.8 + /- 2.1 to 23.2 + /- 1.5 mL/kg/minute vs control group = 23.4 + /- 1.6 to 20.9 + /- 2.2 mL/kg/minute ; P < .05 ) , high-density lipoprotein ( HDL ) cholesterol ( exercise group = 1.02 + /- 0.03 to 1.10 + /- 0.04 mmol/L vs control group = 1.08 + /- 0.07 to 0.99 + /- 0.09 mmol/L ; P < .05 ) , and FMD area under the curve ( AUC ) ( exercise group = 746 + /- 66 to 919 + /- 94 % * sec vs control group = 731 + /- 102 to 515 + /- 73 % * sec ; P < .05 ) . CONCLUSIONS In overweight children and adolescents , CRP is independently associated with fasting insulin . Eight weeks of aerobic exercise improves fitness , HDL cholesterol , and endothelial function in this group Abstract Objective : To determine the effects of a home-based strength training ( HBST ) intervention on insulin sensitivity ( SI ) , compensatory acute insulin response and β-cell function , body composition measures , and maximum strength in obese Latino boys . Methods : A total of 26 obese Latino males aged between 14 and 18 years were r and omized to either a twice-weekly ( n=15 ) or a control group ( C ; n=15 ) for 16 weeks . HBST for 16 weeks , composed of two 1-h sessions per week . Outcome measures were assessed pre- and post-intervention/control condition and included SI , acute insulin response to glucose ( AIR ) and disposition index ( DI ) , fasting glucose , 2-h glucose , body composition using waist-hip circumferences , body mass index ( BMI ) , dual energy X-ray absorptiometry ( DEXA ) scan , blood pressure , and strength by 1-repetition maximum . A repeated measures GLM was used to assess differences in changes in outcome measures , between the C and the HBST groups . Results : There were no significant overall intervention effects on any of the outcome variables ( p<0.05 ) . Conclusion : These results suggest that an HBST does not improve SI , maximal strength or decrease adiposity in obese Latino boys Abstract Nobre , GG , de Almeida , MB , Nobre , IG , dos Santos , FK , Brinco , RA , Arruda-Lima , TR , de-Vasconcelos , KL , de-Lima , JG , Borba-Neto , ME , Damasceno-Rodrigues , EM , Santos-Silva , SM , Le and ro , CG , and Moura-dos-Santos , MA . Twelve weeks of plyometric training improves motor performance of 7- to 9-year-old boys who were overweight/obese : a r and omized controlled intervention . J Strength Cond Res 31(8 ) : 2091–2099 , 2017—The prevalence of childhood overweight/obesity has increased , and physical training at school may to be effective to combat this scenario . We analyzed the effects of a protocol of plyometric training on body composition and motor performance of boys who were overweight/obese aged 7–9 years . The sample was r and omly assigned into 2 groups : plyometric training group ( T , n = 40 ) and control group ( C , n = 19 ) . Training consisted of 20 min·d−1 ( twice a week , during 12 weeks ) of lower extremity plyometric exercise . Health-related physical fitness was measured by h and grip strength , st and ing long jump ( SLJ ) , curl-ups , sit and reach , square test , running speed , and mile run test . Gross motor coordination was evaluated by means of the Körperkoordinations-test für Kinder ( KTK ) tests . Baseline and postintervention differences were investigated , and effect size was estimated through Cohen 's d coefficient . Both groups showed increased body weight , height , and sitting height after intervention with a negligible effect size . Only T group showed increased fat-free mass ( p = 0.011 ) compared with baseline values with small effect size . Plyometric training improved h and grip strength ( d = 0.23 ) , sit and reach ( d = 0.18 ) , curl-ups ( d = 0.39 ) , SLJ ( d = 0.80 ) , agility ( d = 0.48 ) , and time in the mile run test ( d = 0.38 ) . For gross motor coordination results , T group showed better performance in all tests after plyometric training with moderate/large effect size . Thus , 12 weeks of PT improved health-related physical fitness components and motor coordination acquisition of 7- to 9-year-old boys who were overweight/obese We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults , aged ( mean ± SE ) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m2 . Subjects were admitted to the NIH Clinical Center and r and omized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks . Meals were design ed to be matched for presented calories , energy density , macronutrients , sugar , sodium , and fiber . Subjects were instructed to consume as much or as little as desired . Energy intake was greater during the ultra-processed diet ( 508 ± 106 kcal/day ; p = 0.0001 ) , with increased consumption of carbohydrate ( 280 ± 54 kcal/day ; p < 0.0001 ) and fat ( 230 ± 53 kcal/day ; p = 0.0004 ) , but not protein ( -2 ± 12 kcal/day ; p = 0.85 ) . Weight changes were highly correlated with energy intake ( r = 0.8 , p < 0.0001 ) , with participants gaining 0.9 ± 0.3 kg ( p = 0.009 ) during the ultra-processed diet and losing 0.9 ± 0.3 kg ( p = 0.007 ) during the unprocessed diet . Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment This study aim ed to determine whether aerobic training could reduce lipid peroxidation and inflammation at rest and after maximal exhaustive exercise in overweight/obese adolescent girls . Thirty-nine adolescent girls ( 14 - 19 years old ) were classified as nonobese or overweight/obese and then r and omly assigned to either the nontrained or trained group ( 12-week multivariate aerobic training program ) . Measurements at the beginning of the experiment and at 3 months consisted of body composition , aerobic fitness ( VO2peak ) and the following blood assays : pre- and postexercise lipid peroxidation ( 15F2a-isoprostanes [ F2-Isop ] , lipid hydroperoxide [ ROOH ] , oxidized LDL [ ox-LDL ] ) and inflammation ( myeloperoxidase [ MPO ] ) markers . In the overweight/ obese group , the training program significantly increased their fat-free mass ( FFM ) and decreased their percentage of fat mass ( % FM ) and hip circumference but did not modify their VO2peak . Conversely , in the nontrained overweight/obese group , weight and % FM increased , and VO2peak decreased , during the same period . Training also prevented exercise-induced lipid peroxidation and /or inflammation in overweight/obese girls ( F2-Isop , ROOH , ox-LDL , MPO ) . In addition , in the trained overweight/obese group , exercise-induced changes in ROOH , ox-LDL and F2-Isop were correlated with improvements in anthropometric parameters ( waist-to-hip ratio , % FM and FFM ) . In conclusion aerobic training increased tolerance to exercise-induced oxidative stress in overweight/obese adolescent girls partly as a result of improved body composition Purpose We investigate the effects of 12-week interval training of moderate- or high-intensity exercise on blood lipids and plasma levels of adiponectin . Methods Thirty-four obese adolescent females [ age = 15.9 ± 0.3 years ; BMI and BMI -Z-score = 30.8 ± 1.6 kg/m2 and 3 ± 0.3 , respectively ] , were r and omized to high-intensity interval training ( HIIT , n = 11 ) , moderate-intensity interval training ( MIIT , n = 11 ) , or a control group ( CG , n = 12 ) . Maximal oxygen uptake ( $ $ \mathop V\limits^{. } { \text{O}}_{{2{\text{peak}}}}$$V.O2peak ) , maximal aerobic speed ( MAS ) , plasma lipids and adiponectin levels were measured in all subjects before and after training . Results Following the training program , in both training groups , body mass , BMI -Z-score , and percentage body fat ( % BF ) decreased , while $ $ \mathop V\limits^{. } { \text{O}}_{{2{\text{peak}}}}$$V.O2peak and MAS increased . Low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and adiponectin levels were positively altered ( −12.6 and −7.4 % ; 6.3 and 8.0 % ; 35.8 and 16.2 % ; high to moderate training program , respectively ) . Waist circumference , triglyceride and total cholesterol decreased only in HIIT group ( −3.5 ; −5.3 and −7.0 % , respectively , in all P < 0.05 ) . Significant decrease in the usual index of insulin resistance ( HOMA-IR ) occurred in HIIT and MIIT groups ( −29.2 ± 5.3 and −18.4 ± 8.6 % , respectively ; P < 0.01 ) . Conclusion The results show that HIIT positively changes blood lipids and adiponectin variables in obese adolescent girls , result ing in improved insulin sensitivity , as attested by a lower HOMA-IR , and achieving better results compared to moderate-intensity exercise Abstract Objective : To assess the effects of resistance exercise training on body composition and muscular strength in obese prepubertal children . Design : Study participants , who were between the ages of 8 and 12 years , met Tanner I ( stage ) criteria , had a body mass index ⩾ 95th percentile for age and sex , were r and omized to either high-repetition , moderate-intensity resistance training ( n = 12 ) or to the non-intervention control group ( n = 7 ) for 12 weeks . Exercise training was performed twice a week for 75 minutes per session . Body composition was assessed using dual energy x-ray absorptiometry and muscular strength was evaluated using a 1-repetition-maximum test . Results : Exercise-group participants attended 98 % of the 24 total sessions and showed a significant increase in body weight ( 57.6 ± 13.5 vs 59.6 ± 14.1 kg ) , height ( 144.9 ± 9 vs 146.6 ± 10.4 cm ) , lean body mass ( 32.6 ± 6.8 vs 34.0 ± 7.0 kg ) , lean body mass index ( lean body mass in kg/height2 ; 15.3 ± 1.6 vs 15.6 ± 1.5 kg/m2 ) , arm strength ( 28.4 ± 5.8 vs 31.2 ± 6.0 kg ) , and leg strength ( 89.4 ± 31.7 vs 113.4 ± 34 2 kg ) from baseline measures ( P < 0.05 ) . Control group participants also showed significant increases in weight , height , and lean body mass from baseline measures ( P < 0.05 ) but not in arm or leg strength . When the changes in participant body composition and muscular strength were compared between the exercise and control groups , significant differences were found in leg lean mass and leg strength ( P < 0.05 ) . There were no changes in percent body fat and fat mass index [ FM/height2 ( kg/m2 ) ] in either group . Conclusion : Resistance training increases leg lean mass and leg strength in obese prepubertal youth and may have a positive effect on overall physical activity and health |
2,125 | 31,792,939 | The evidence base for other interventions is smaller , and does not provide sufficient information to determine whether there are important differences between pressure modification strategies and fixed CPAP on machine usage outcomes , symptoms and quality of life .
In adults with moderate to severe sleep apnoea starting positive airway pressure therapy , auto-CPAP probably increases machine usage by about 13 minutes per night .
The effects on daytime sleepiness scores with auto-CPAP are not clinical ly meaningful .
AHI values are slightly lower with fixed CPAP . | BACKGROUND Obstructive sleep apnoea ( OSA ) is the repetitive closure of the upper airway during sleep .
This results in disturbed sleep and excessive daytime sleepiness .
It is a risk factor for long-term cardiovascular morbidity .
Continuous positive airway pressure ( CPAP ) machines can be applied during sleep .
They deliver air pressure by a nasal or oronasal mask to prevent the airway from closing , reducing sleep disturbance and improving sleep quality .
Some people find them difficult to tolerate because of high pressure levels and other symptoms such as a dry mouth .
Switching to machines that vary the level of air pressure required to reduce sleep disturbance could increase comfort and promote more regular use .
Humidification devices humidify the air that is delivered to the upper airway through the CPAP circuit .
Humidification may reduce dryness of the throat and mouth and thus improve CPAP tolerability .
This up date d Cochrane Review looks at modifying the delivery of positive pressure and humidification on machine usage and other clinical outcomes in OSA .
OBJECTIVES To determine the effects of positive pressure modification or humidification on increasing CPAP machine usage in adults with OSA . | Background and aims Manual laboratory continuous positive airway pressure ( CPAP ) titration for obstructive sleep apnoea ( OSA ) is costly , time intensive and delays access to treatment . Automatic positive airway pressure ( APAP ) titration has the potential to reduce cost and improve access to treatment . The aim of this study was to assess the clinical efficacy and costs of APAP titration compared with manual titration in moderate – severe OSA . Methods Patients with moderate – severe OSA ( apnoea/hypopnoea index > 15 and Epworth Sleepiness Score ≥8 ) who were free of co-morbidities that could impair APAP titration were eligible . 249 participants were r and omised to manual titration , home APAP or laboratory APAP titration to determine a fixed pressure for CPAP . Clinical and direct cost outcomes were assessed after 4 weeks of treatment . Results Average nightly CPAP use , subjective sleepiness , SF36 quality of life , Trails A and B cognitive function and polysomnographic outcomes were similar among the per- protocol groups . Non-hypertensive patients had a lower resting heart rate ( and greater reduction in heart rate ) at 4 weeks after laboratory APAP titration compared with home APAP titration . Costs per patient were highest in manual ( AU$817.84 ) , followed by laboratory ( AU$647.56 ) and home ( AU$132.09 ) APAP titration . An intention-to-treat analysis confirmed the effectiveness of APAP titration compared with manual titration in the st and ard clinical setting . Conclusions Among patients with moderate – severe OSA without serious co-morbidities , outcomes at 1 month indicate that APAP titration is more cost-effective than manual laboratory titration to determine an appropriate pressure for CPAP for long-term use ; with the largest savings occurring in the home APAP patients . Australian New Zeal and Clinical Trials Registry Number ACTRN12608000054314 BACKGROUND Obstructive sleep apnea syndrome ( OSAS ) has been associated with increased morbidity and mortality , principally from cardiovascular disease , but the impact of nasal continuous positive airway pressure ( CPAP ) therapy is unclear . METHODS We performed a long-term follow-up study of 168 patients with OSAS who had begun receiving CPAP therapy at least 5 years previously , most of whom had been prospect ively followed up , having been the subject of an earlier report on cardiovascular risk factors in OSAS patients . The average follow-up period was 7.5 years . We compared the cardiovascular outcomes of those patients who were intolerant of CPAP ( untreated group , 61 patients ) with those continuing CPAP therapy ( 107 patients ) . RESULTS CPAP-treated patients had a higher median apnea-hypopnea index score than the untreated group ( 48.3 [ interquartile range ( IQR ) , 33.6 to 66.4 ] vs 36.7 [ IQR , 27.4 to 55 ] , respectively ; p = 0.02 ) , but age , body mass index , and time since diagnosis were similar . Deaths from cardiovascular disease were more common in the untreated group than in the CPAP-treated group during follow-up ( 14.8 % vs 1.9 % , respectively ; p = 0.009 [ log rank test ] ) , but no significant differences were found in the development of new cases of hypertension , cardiac disorder , or stroke . Total cardiovascular events ( ie , death and new cardiovascular disease combined ) were more common in the untreated group than in the CPAP-treated group ( 31 % vs 18 % , respectively ; p < 0.05 ) . CONCLUSIONS The data support a protective effect of CPAP therapy against death from cardiovascular disease in patients with OSAS OBJECTIVES To study the effects of augmentation of continuous positive airway pressure ( CPAP ) education and support on compliance and outcome in patients with obstructive sleep apnea ( OSA ) . DESIGN A r and omized , controlled , parallel study of basic vs augmented CPAP education and support . SETTING A university teaching hospital . PATIENTS A total of 108 OSA patients r and omized into basic-support ( BS ) and augmented-support ( AS ) groups . INTERVENTIONS Patients in the BS group ( n = 54 ) were given educational brochures on OSA and CPAP , CPAP education by nurses , CPAP acclimatization , and were review ed by physicians and nurses at weeks 4 and 12 . Patients in the AS group ( n = 54 ) received more education , including a videotape , telephone support by nurses , and early review at weeks 1 and 2 . MEASUREMENTS Objective CPAP compliance , Calgary sleep apnea quality of life index ( SAQLI ) , and cognitive function after 1 month and 3 months ; and Epworth sleepiness scale ( ESS ) after 3 months of CPAP treatment . RESULTS At 4 weeks , CPAP usage was 5.3 + /- 0.2 h/night ( mean + /- SEM ) vs 5.5 + /- 0.2 h/night in the BS and AS groups , respectively ( p = 0.4 ) . At 12 weeks , CPAP usage was 5.3 + /- 0.3 h/night vs 5.3 + /- 0.2 h/night in the two groups , respectively ( p = 0.98 ) . There was greater improvement of SAQLI at 4 weeks ( p = 0.008 ) and at 12 weeks ( p = 0.047 ) in the AS group . There was no significant difference between BS and AS groups in terms of improvement of ESS and cognitive function . CONCLUSION Augmentation of CPAP education and support does not increase CPAP compliance , but leads to a greater improvement of quality of life during the reinforced period Background Following the World Trade Center disaster , a large number of individuals involved in rescue and recovery activity were exposed to significant amounts of dust , and reported symptoms of chronic nasal and sinus inflammation . An unusually high prevalence of obstructive sleep apnea ( OSA ) has also been observed in this World Trade Center Responder population . This project aims to examine the relationship between nasal pathology and OSA . Our hypothesis is that increased nasal resistance due to nasal inflammation predisposes to OSA in this population . Continuous Positive Airway Pressure ( CPAP ) is the st and ard therapy for OSA but despite its efficacy has poor adherence . Subjects with high nasal resistance may have greater difficulty in tolerating this therapy than those who do not have high nasal resistance . Reduction of excess expiratory positive pressure by the modality known as Cflex ™ during Continuous Positive Airway Pressure therapy ( CPAPFlex ) has been suggested to improve comfort without compromising efficacy . We will compare CPAP to CPAPFlex in subjects with OSA . Study Design Subjects with new onset habitual snoring will be screened for OSA using home sleep studies and rhinomanometry will be used to determine nasal resistance . In 400 subjects with OSA we will perform a r and omized double blind cross-over study comparing CPAP to CPAPflex , and relate nasal resistance to adherence to CPAP therapy . Discussion This is the first multicenter trial design ed to test the hypothesis that adherence to CPAP therapy relates to nasal resistance and CPAPFlex will improve adherence to CPAP in those subjects with high nasal resistance . We anticipate the following results from this trial : 1 . Increased nasal resistance is associated with decreased adherence to CPAP therapy . 2 . Use of CPAPFlex improves adherence with CPAP therapy in subjects with high nasal resistance , but not in those with low nasal resistance . 3 . The benefit of CPAPFlex on adherence is greatest when offered at CPAP therapy initiation rather than as a “ rescue ” therapy in subjects with high nasal resistance . Trial Registration Clinical Trials.gov Identifier : NCT01753999 , Date : 12 December STUDY OBJECTIVES To compare conventional and self-adjusting nasal continuous positive airway pressure ( nCPAP ) therapy in patients with severe obstructive sleep apnea syndrome with respect to suppression of respiratory disturbances , quality of sleep , mean mask pressure , and patient compliance . DESIGN Cohort study of consecutive patients with obstructive sleep apnea syndrome , single-blinded . SETTING Clinical sleep laboratory in Germany . PATIENTS Fifty patients ( 44 men , 6 women who ranged in age from 35 to 71 years ) with polysomnographically confirmed severe obstructive sleep apnea syndrome ( respiratory disturbance index [ RDI ] , > 20/h ) . MEASUREMENTS AND INTERVENTIONS After baseline polysomnography , patients were r and omly treated with nCPAP either in conventional ( group 1 ) or in automatically adjusting ( group 2 ) mode . Three to 6 months after adjustment , all patients underwent polysomnography again . They also were examined with a portable monitoring device and received a question naire on subjective well-being and device evaluation . RESULTS Anthropometric and respiratory data were comparable in both groups ; body mass index had not changed significantly in the follow-up . RDI dropped by 91.5 % ( from 38.3+/- 13.9/h to 3.6+/-4.4/h ) in conventional and by 93.6 % ( from 35.5+/-9.6/h to 2.4+/-1.6/h ) in self-adjusting mode ( statistically not significant [ NS ] ) . Sleep efficiency decreased by 4.0 % in conventional and increased by 2.0 % in self-adjusting mode ( NS ) . In both groups , normal sleep structure was largely restored . Mean mask pressure was 8.1+/-2.5 cm H2O in group 1 and 6.5+/-1.7 cm H2O in group 2 ( p<0.01 ) . Patient compliance in terms of nights per week of mask appliance was better in the self-adjusting mode ( 5.7+/-0.7 to 6.5+/-0.4 ; p<0.01 ) . CONCLUSION Self-adjusting nCPAP demonstrates the same reliability in suppression of respiratory disturbances as fixed-mask pressure therapy . Sleep quality is slightly superior , patient compliance is highly significantly better The first generation of Auto CPAP devices caused respiratory arousal by apnoes , hypopnoeas , incomplete obstructions and pressurechanges . The new , second generation of CPAP devices which is based on forced oscillation technique will change the pressure with slower velocity and before the respiratory arousal reaction will occur ( 1 , 9 , 10 ) . Fifty patients with severe sleep apnoea ( AHI 66±26 /h ) were treated with both , constant- CPAP ( continous positive airway pressure ) or Auto CPAP under polysomnographic control in a r and omised order . The Auto CPAP based on forced oscillation technique reduced the number of apnoeas and hypopnoeas as did most of the other Auto CPAP systems to AHI 2.5±5.9 /h ( p<0.05 ) . In comparison to Auto CPAP of the first generation it also decreased the number of respiratory arousal reactions caused by apnoeas and hypopnoeas . However there is still a significant difference to number of arousal detected with constant CPAP ( p<0.01 ) . In conclusion although the new generation of Auto CPAP reduced the number of respiratory arousals compared to first generation , we did not find a therapeutical benefit for patients with severe SAS Daytime CPAP titration studies with full polysomnography have been successfully performed in patients with severe sleep apnea-hypopnea syndrome ( SAHS ) . The implementation of daytime studies in unselected SAHS patients could help to reduce the waiting lists for CPAP titrations . The main purpose of this study was to compare the effectiveness of conventional versus manual or automatic daytime CPAP titration in unselected patients with SAHS . Ninety-three consecutive patients with SAHS in whom CPAP was indicated were assigned to conventional titration or to manual or automatic ( AutoSet ) daytime CPAP titration , after sleep deprivation . The number of valid studies , sleep architecture , final pressure selected and mean pressure in the different sleep stages were compared . Changes in sleepiness ( Epworth sleepiness score ) and hours of CPAP use were assessed after 3 months of treatment . Four patients did not sleep ( 3 AutoSet , 1 conventional daytime groups ) . Sleep latency was shorter during automatic daytime titration whereas REM latency was shorter in daytime studies ; the percentage of sleep stages was similar during all types of titration . CPAP requirements were significantly higher during REM sleep in conventional and manual daytime titrations while mean pressure was unchanged throughout sleep stages during AutoSet titration . CPAP pressure selected with conventional or daytime manual titration ( 7.5(2.2 ) cm H2O and 7.4(1.5 ) cm H2O , ns ) were significantly lower ( P < 0.001 ) than with AutoSet ( 9.4(1.6 ) cm H20 . All groups showed similar decrease of sleepiness and hours of use of CPAP at 3 months of follow-up . Automatic and manual daytime PSG studies after sleep deprivation are useful for CPAP titration in unselected patients with SAHS . Pressure selected with AutoSet is significantly higher than with conventional daytime or nighttime titration , although not significant in terms of treatment compliance and symptom improvement Autoadjusting nasal continuous positive airway pressure ( CPAP ) greatly reduces the apnoea/hypopnoea index ( AHI ) , and affords a significant reduction in median pressure ( P50 ) compared-with manually titrated conventional nasal CPAP . The aim of the present study was to test whether these benefits were maintained in the medium term at home , in a double-blind crossover study . Ten sequential subjects ( mean AHI 52.9 x h(-1 ) ) were enrolled . After a manual titration , subjects were r and omly allocated to 2 months autoadjusting nasal CPAP ( AutoSet ) , followed by 2 months with the AutoSet device in fixed pressure mode at the manually titrated pressure , or vice versa . The machine-scored AHI , P50 , and median leak were recorded on 12 nights in each arm , and averaged . Mean+/-SEM AHI was 4.0+/-0.3 x h(-1 ) in auto mode , and 3.7+/-0.3 x h(-1 ) in manual mode ( NS ) . Mean+/-SEM P50 was 7.2+/-0.4 cmH2O auto , 9.4+/-0.6 cmH2O manual , average reduction 23+/-4 % ( p<0.0001 ) . Auto " recommended " pressure was ( mean+/-SEM ) 10.1+/-0.5 cmH2O ( p=0.04 with respect to manual ) and peak pressure typically 1 cmH2O higher . Median ( + /-SEM ) leak was 0.181+/-0.006 L x s(-1 ) auto ( and uncorrelated with AHI or pressure ) , 0.20+/-0.006 L x s(-1 ) manual ( p=0.003 ) . Compliance was 6.3+/-0.4 h in auto mode and 6.1+/-0.5 h in fixed mode ( NS ) . Apnoea/hypopnoea index during 2 months of home autoadjusting nasal continuous positive airway pressure is comparable to that during conventionally titrated fixed pressure continuous positive airway pressure , while affording a 23 % reduction in median pressure but no increase in compliance . Leak did not importantly affect autoadjustment The present study objective was to establish whether pretreatment social cognitive variables may contribute to the explanation of variance in adherence to continuous positive airway pressure ( CPAP ) treatment for patients with obstructive sleep apnoea/hypopnoea syndrome ( OSAHS ) . A total of 119 of 180 consecutive OSAHS patients were recruited to the study prior to initial CPAP titration . Patients completed psychological measures of health value , health locus of control ( incorporating internality , chance , powerful others ) and self-efficacy prior to CPAP titration . Objective adherence data were measured by CPAP unit time clocks and collected at 3-month follow-up . Average nightly use was calculated over this period . Logistic regression of prospect i ve predictors of adherence produced a model comprising psychological ( health value , internality , powerful others ) , as well as clinical variables ( Epworth score , body mass index , apnoea/hypopnoea index , CPAP pressure ) . This model explained 24 % of the variance in CPAP use , and correctly identified 75 % of adherers and 53 % of nonadherers . Although the psychological variables explained only a small amount of the overall variance in adherence behaviour , this result provides further support for the hypothesis that psychological variables contribute , in part , to continuous positive airway pressure adherence . Future research should focus on highlighting discrete variables , which may helpfully inform psychologically based interventions aim ed at improving the use of continuous positive airway pressure by patients with obstructive sleep apnoea/hypopnoea syndrome at risk of discontinuance Background : The simplest method of initiating and maintaining therapeutic continuous positive airways pressure ( CPAP ) therapy for obstructive sleep apnoea ( OSA ) has not been established . Methods : Ninety eight subjects with OSA requiring CPAP treatment ( more than 10 dips in oxygen desaturation of > 4 % per hour of sleep study and Epworth Sleepiness Score ( ESS ) > 9 ) were r and omised prospect ively to three different methods of CPAP delivery for 6 months : ( 1 ) autotitration pressure throughout ; ( 2 ) autotitration pressure for 1 week followed by fixed pressure ( 95th centile ) thereafter ; and ( 3 ) fixed pressure determined by algorithm ( based on neck size and dip rate ) . Patients and investigators were blind to group allocation . One week after initiation the patients were routinely review ed by sleep nurses . Study assessment s took place before starting CPAP treatment and 1 and 6 months after to assess ESS , maintenance of wakefulness test , 24 hour blood pressure , general health ( SF-36 ) , and sleep apnoea related quality of life . CPAP internal monitoring data were also collected . Results : There were no significant differences in any of the outcome measures or CPAP monitoring data between the three groups . The 95th centile CPAP pressures delivered in the 6 month and 1 week autotitration groups were higher than in the algorithm group , but the median pressures were lowest in the 6 month autotitration group . Conclusions : The method of determining CPAP pressure for treatment of moderate to severe OSA makes no significant difference to clinical outcome measures . The autotitration CPAP machine used has no advantage in this setting over simpler methods of pressure determination The present study examined the efficacy of a cognitive-behavioral intervention at improving compliance with CPAP and vigilance in older adults with obstructive sleep apnea/hypopnea syndrome ( OSAHS ) . Participants included 12 subjects who were r and omized into one of two groups controlling for age , education , disease severity , and vigilance . The experimental group received two 45-min sessions design ed to educate subjects on the consequences of OSAHS and the efficacy of CPAP . The control group received the same extent of therapist contact but did not receive information on OSAHS or CPAP . All subjects were administered a test of vigilance both before and after the study . Compliance data were collected using CPAP devices with internal microprocessors at were read at 1 , 4 , and 12 weeks after treatment initiation . The results showed that the experimental condition did not enhance compliance after 1 week of treatment but did so by the 12-week follow-up . Subjects in the experimental condition had a run time of 3.2-h per night longer than did those in the control group . Those using CPAP more regularly at 12 weeks also showed greater improvement on vigilance at follow-up . Performance on vigilance testing before the introduction of CPAP was predictive of CPAP use at 12 weeks . In conclusion , a modest cognitive-behavioral intervention may substantially increase CPAP use and vigilance in older adults An automated positive airway pressure device that monitors respiratory patterns and provides dynamic , real-time , relational pressure has been developed for the treatment of obstructive sleep apnea ( OSA ) . The purpose of this study was to compare self-adjusting pressure to classical nasal continuous positive airway pressure ( NCPAP ) . Subjects were newly diagnosed patients with a minimum respiratory disturbance index ( RDI ) of 15 episodes per hour who had undergone NCPAP titration and been using classical NCPAP at home on a nightly basis for at least 2 weeks . Patients then underwent repeat st and ard polysomnographic ( PSG ) evaluations for 2 nights using a self-adjusting pressure mode and a st and ard NCPAP mode r and omly assigned in a single-blind crossover fashion . Eight males and four females ( n = 12 ) , aged 48.4 + /- 12.2 years [ mean + /- and st and ard deviation ( SD ) ] , completed the study . During initial diagnostic PSG , the RDI was 57.3 + /- 30.8 episodes per hour . The RDI and minimum oxygen saturation for both treatment nights were significantly improved from those of the diagnostic PSGs ( p < 0.001 ) . The subjects spent 63.1 + /- 34.2 % of total sleep time below prescribed pressure while on automatic pressure Percent of total sleep time in stage 3/4 sleep was significantly higher during self-adjusting pressure , at 8.6 + /- 7.5 % , compared to st and ard NCPAP , at 4.6 + /- 6.0 % ( p < 0.05 ) . Computerized adjustable nasal positive airway pressure effectively controls OSA , fluidly providing the minimal pressure necessary to control respiratory events without causing sleep disruption STUDY OBJECTIVES To compare the efficacy and patient tolerance , compliance , and preference between auto-continuous positive airway pressure ( CPAP ) and constant CPAP . DESIGN Single-blinded , crossover , cohort study of consecutive patients with obstructive sleep apnea syndrome , with two treatment periods of 2 months each . PATIENTS Twenty-five patients ( 22 men , 3 women ) with sleep apnea syndrome confirmed by ambulatory polysomnography . MEASUREMENTS AND INTERVENTIONS After baseline polysomnography , patients underwent in-laboratory polysomnography for titration of constant CPAP . The order of treatment was r and omly allocated , either auto-CPAP and then constant CPAP , or vice versa . The auto-CPAP pressure range was 6 to 16 cm H(2)O. At the end of each 2-month period , patients underwent a control ambulatory polysomnography and received a question naire on subjective well-being and device evaluation . Duration of use was checked through CPAP device monitoring . RESULTS No differences were found in apnea/hypopnea index ( constant CPAP , 9.7+/-1.9 events/h vs auto-CPAP , 10.6+/-9.3 events/h ) , awakening/arousal index ( constant CPAP , 13.7 + /- 8.0 events/h vs auto-CPAP , 15.5 + /- 8.9 events/h ) , slow-wave sleep duration , nocturnal saturation , or complaint of daytime sleepiness . The mean pressure required was significantly lower during auto-CPAP than during constant CPAP ( 8.8+/-1.8 cm H(2)O vs. 9.7+/-2.6 cm H(2)O , respectively ) . Patient tolerance , compliance , and duration of use were similar with both treatments . CONCLUSIONS Auto-CPAP is as effective as constant CPAP . A wide pressure range for auto-CPAP can be used in all patients , suggesting that , in the future , use of a broad pressure range in the auto-CPAP mode could obviate the need for the titration night The influence of sleep stage- and body position-dependence of sleep apnoea on treatment efficacy and compliance between conventional continuous positive airway pressure ( CPAP ) and auto CPAP therapy was evaluated . Thirty-three newly treated sleep apnoea hypopnoea syndrome ( SAHS ) patients were r and omly allocated to conventional or auto-CPAP therapy . Six patients of each treatment group were classified as having sleep stage- and body position-dependent obstructive breathing abnormalities according to the results of the baseline sleep study . After 3 weeks of treatment , the Epworth sleepiness score tended to be higher ( p = 0.08 ) and the ability to stay awake lower ( p = 0.02 ) in patients with dependent breathing abnormalities treated with fixed CPAP , than in the other patients . The effective pressure/time index was significantly lower in sleep stage- and body position-dependent patients treated with fixed CPAP , than in the other patients ( p = 0.02 ) . The number of hours the machine was turned on and a positive pressure applied , tended to be smaller in dependent patients treated with fixed CPAP than in independent patients of this treatment group and in patients treated with auto-CPAP . A night-to-night variability index ( VI ) of positive pressure changes was obtained in the auto-CPAP group . This index significantly decreased with time in the dependent patients while it remained unchanged in the independent group . It is concluded that auto-continuous positive airway pressure may have specific indications in a subset of obstructive sleep apnoea patients with sleep stage- and body position dependent nocturnal breathing abnormalities Background Despite the efficacy of continuous positive airway pressure ( CPAP ) for the treatment of obstructive sleep apnea ( OSA ) , compliance with therapy remains suboptimal . The aim of this study was to determine whether the use of S9TM increased compliance in established CPAP users . Methods Subjects with OSA ( 50 ) were recruited into the study . When subjects entered the study , 28 days of respective compliance data were downloaded from the patient 's usual CPAP device . Subjects trialled the S9 CPAP for 28 days . Subjects then resumed use of their usual CPAP for 28 days . Compliance data from the patient 's usual CPAP pre- and post-trialling S9 were compared with data from the S9 CPAP . Results Patients were significantly more compliant when using the S9 than their usual CPAP device both pre- and post-S9 based on average daily usage . CPAP pre-S9 = 6.58 ± 1.95 ( mean hours ± SD ) , S9 = 7.08 ± 1.18 h and CPAP post-S9 = 6.71 ± 1.72 h. The difference between CPAP pre-S9 and S9 was 0.5 h ( p = 0.003 ) . The difference between S9 and CPAP post-S9 was 0.35 h ( p = 0.01 ) . There was no significant difference between CPAP pre-S9 and CPAP post-S9 ( p = 0.34 ) . Patients also completed question naires comparing the S9 system to their usual device . Subjective feedback showed a strong preference for the S9 . Conclusions Participants were significantly more compliant when using the S9 than their usual CPAP device both pre- and post-S9 use STUDY OBJECTIVES Measures of health-related quality of life ( HRQL ) specific for sleep disorders have had limited psychometric evaluation in the context of r and omized controlled trials ( RCTs ) . We investigated the psychometric properties of the Functional Outcomes of Sleep Question naire ( FOSQ ) and Sleep Apnea Quality of Life Instrument ( SAQLI ) . We evaluated the FOSQ and SAQLI construct and criterion validity , determined a minimally important difference , and assessed for associations of responsiveness to baseline subject characteristics and continuous positive airway pressure ( CPAP ) adherence in a RCT population . DESIGN Secondary analysis of data collected in a multisite RCT of home versus laboratory-based diagnosis and treatment of obstructive sleep apnea ( HomePAP trial ) . PARTICIPANTS Individuals enrolled in the HomePAP trial ( n = 335 ) . INTERVENTIONS N/A. MEASUREMENT AND RESULTS The FOSQ and SAQLI subscores demonstrated high reliability and criterion validity , correlating with Medical Outcomes Study 36-Item Short Form Survey domains . Correlations were weaker with the Epworth Sleepiness Scale ( ESS ) . Both the FOSQ and SAQLI scores improved after 3 mo with CPAP therapy . Averaging 4 h or more of CPAP use was associated with an increase in the FOSQ beyond the minimally important difference . Baseline depressive symptoms and sleepiness predicted FOSQ and SAQLI responsiveness ; demographic , objective obstructive sleep apnea ( OSA ) severity and sleep habits were not predictive in linear regression . CONCLUSIONS The FOSQ and SAQLI are responsive to CPAP intervention , with the FOSQ being more sensitive to differences in CPAP adherence than the SAQLI . These instruments provide unique information about health outcomes beyond that provided by changes in physiological measures of OSA severity ( apnea-hypopnea index ) . CLINICAL TRIAL INFORMATION Portable Monitoring for Diagnosis and Management of Sleep Apnea ( HomePAP ) URL : http:// clinical trials.gov/show/NCT00642486 . NIH clinical trials registry number : NCT00642486 Background Continuous positive airway pressure ( CPAP ) devices with the option of flexible pressure delivery ( e.g. , C-Flex ) are thought to provide an improved degree of comfort and result in better therapeutic adherence while maintaining st and ard CPAP efficacy . The purpose of this study was to compare adherence and subjective measures of comfort between C-Flex and CPAP treatment . Methods The study was an international , multisite , single-blinded study with participants r and omized to either C-Flex or CPAP . Participants completed subjective measures of sleepiness and comfort at baseline , and at 30- , 90- , and 180-day follow-ups . Additionally , compliance data were downloaded from the device at each follow-up . Repeated measures analysis of variance was used to assess the effects of treatment . Results There were 138 men and 46 women ( average age of 48 ± 9.2 , average Epworth Sleepiness Scale score of 14.9 ± 3.6 , and average diagnostic apnea/hypopnea index ( AHI ) of 51.9 ± 27.7 ) . C-Flex and CPAP groups were comparable on baseline measures , achieved comparable AHI on titration , and had comparable PAP pressure requirements . C-Flex users had comparable average hours of use per night and total nights of use across the study , but had a trend ( p < .07 ) toward achieving greater total hours of utilization . While both groups had comparable decreases in sleepiness , C-Flex users reported on visual analog scales greater comfort ( 64.3 vs. 57.4 ; p = .01 ) . Conclusions The results of this study demonstrated that C-Flex has comparable resolution of respiratory indices and adherence . Furthermore , C-Flex users reported greater mask comfort Abstract Psychological symptom improvement has been observed after continuous positive airway pressure ( CPAP ) treatment of obstructive sleep apnea ( OSA ) . Because CPAP normalizes both sleep disruption and oxyhemoglobin desaturation , the mechanism of psychological symptom improvement is unclear . Using a 3-arm placebo-controlled design , we parsed out the separate effects of treatment on psychological symptoms . OSA patients ( N = 38 ) were monitored 2 nights with polysomnography and then r and omized to 2-weeks therapeutic CPAP , placebo CPAP , or O2 supplementation . Pre- and post-treatment , patients completed the Brief Symptom Inventory ( BSI ) : Higher scores indicate greater severity . Repeated measures analysis of covariance reveals a Time × Treatment interaction for BSI Global Severity Index ( GSI ) : significant pre- to post-treatment reductions in GSI with O2 supplementation and therapeutic CPAP , but not placebo CPAP . A Time × Treatment interaction was also found for depression : Depression decreased with O2 supplementation but not with therapeutic CPAP or placebo CPAP . Both therapeutic CPAP and O2 supplementation result ed in decreased psychological symptoms . Results suggest hypoxemia may play a stronger role than sleep disruption vis-à-vis OSA related psychological distress The long-term acceptability of treatment with nasal continuous positive airway pressure ( CPAP ) was studied prospect ively in 44 patients with obstructive sleep apnea syndrome . At 14 months on the average after starting treatment with CPAP , 30 patients ( 68 percent ) were found to be compliant ( characterized by use of the apparatus every night throughout the night , for more than 5 h per night ) . The daily use of nasal CPAP was significantly correlated to the initial apnea/hypopnea index ( p = 0.013 ; r = 0.37 ) , as well as to the percentage of light sleep ( p = 0.045 ; r = 0.30 ) and slow-wave sleep ( p = 0.037 ; r = -0.31 ) during the initial polygraphic recording . We found a strong correlation between the daily use of nasal CPAP and the difference in the apnea/hypopnea index ( p = 0.025 ; r = -0.34 ) , the difference in mean oxygen saturation during sleep ( p = 0.013 ; r = 0.38 ) , and the difference in hypersomnia scores ( p = 0.006 ; r = -0.40 ) obtained before and after treatment by nasal CPAP . Thus , patients used CPAP much more if they had an initial significant clinical h and icap and if they were aware of the beneficial effects of CPAP . Under these conditions , patients tended to use the apparatus for the optimal length of time , regardless of the side effects linked to the treatment . This ensured efficacy and the maintenance of good compliance . This study confirms the importance of supervision of the time counter , as well as regular encouragement of patients to use the treatment as long as possible each night , in order to extract a maximum benefit from treatment by nasal CPAP Autotitrating continuous positive airway pressure ( CPAP ) devices automatically adjust the pressure according to upper airway obstructions . The aim of this study was to compare the treatment effects of different automatic CPAP devices ( AutoSet , Horizon and Virtuoso ) with conventional CPAP in patients with obstructive sleep apnoea independently of financial manufacturer support . Twelve male patients with obstructive sleep apnoea were su bmi tted to a crossover study protocol with overnight polysomnography for 6 consecutive nights . After diagnostic polysomnography , the CPAP pressure was manually titrated . Over the next 4 nights , the patients were treated with any one of the three automatic CPAP devices or fixed CPAP in r and om order . The apnoea/hypopnoea index on the diagnostic night was 67.3±21.7 events·h−1 , and was significantly reduced to 0.7±1.2 , 3.0±2.9 , 2.3±2.5 and 12.0±13.6 events·h−1 with the fixed CPAP , AutoSet , Horizon and Virtuoso devices respectively . An apnoea/hypopnoea index of < 5 events·h−1 , an indicator of optimal treatment , was achieved in all patients with fixed CPAP and in 10 patients using the Autoset and Horizon devices , but in only six of the 12 using the Virtuoso . The mean pressure was significantly lower with the AutoSet and Virtuoso devices , but not with the Horizon as compared to fixed CPAP . The maximum pressure was significantly higher with the Horizon . It is concluded that automatic continuous positive airway pressure devices produce a significant reduction in apnoea/hypopnoea index ; however , there is considerable difference in the efficacy of the various devices CONTEXT Few prospect i ve intervention studies have examined the effect of continuous positive airway pressure ( CPAP ) therapy on cardiovascular disease ( CVD ) risk factors in diabetes . OBJECTIVE Our objective was to determine whether CPAP improves CVD risk factors in patients with type 2 diabetes and obstructive sleep apnea ( OSA ) . DESIGN AND SETTING This was a r and omized parallel group intervention trial in an urban Australian community . PATIENTS Fifty-nine participants of the Fremantle Diabetes Study Phase II at high risk for OSA consented to confirmatory polysomnography followed by r and omization to a 3-month CPAP intervention initiated early ( < 1 wk ) or late ( 1 - 2 months ) . MAIN OUTCOME MEASURES Patients were assessed before and 1 and 3 months after CPAP started . Tests for repeated measures were used to compare variables of interest over time . RESULTS Forty-four patients ( 75 % ) completed the study . Their mean ± sd age was 66.1 ± 8.8 yr , and 61.4 % were male . Completers and noncompleters had similar age , sex , diabetes duration , apnea-hypopnea index , and Epworth Sleepiness Scale ( P ≥ 0.29 ) . There were no differences in outcome between early and late r and omization , and the data were pooled . The Epworth Sleepiness Scale decreased between entry and 1 month [ -4.8 ( -6.5 to -3.1 ) , P < 0.001 ] . Blood pressure improved between entry and 3 months ( from 149 ± 23/80 ± 12 to 140 ± 18/73 ± 13 mm Hg ; P ≤ 0.007 ) . Pulse rate declined within the first month [ -6 ( -10 to -2 ) beats/min , P = 0.002 ] . Glycemic control and serum lipids , which were mostly within recommended target ranges at entry , did not change . CONCLUSIONS Three months of CPAP in community-based people with type 2 diabetes significantly decreased blood pressure and pulse rate but did not influence metabolic control STUDY OBJECTIVES To compare adherence and clinical outcomes between flexible positive airway pressure ( PAP ) [ C-Flex ; Respironics ; Murraysville , PA ] and st and ard PAP therapy ( ie , continuous positive airway pressure [ CPAP ] ) . DESIGN AND SETTING A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea . Participants were recruited from and followed up through an academic sleep disorders center . PARTICIPANTS Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy . Participants received either therapy with CPAP ( n = 41 ) or with the C-Flex device ( n = 48 ) , depending on the available treatment at the time of recruitment , with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device . Follow-up assessment s were conducted at 3 months . MEASUREMENTS AND RESULTS The groups were similar demographically . The mean ( + /- SD ) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group ( weeks 2 to 4 , 4.2 + /- 2.4 vs 3.5 + /- 2.8 , respectively ; weeks 9 to 12 , 4.8 + /- 2.4 vs 3.1 + /- 2.8 , respectively ) . Clinical outcomes and attitudes toward treatment ( self-efficacy ) were also measured . Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other . Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment . CONCLUSIONS Therapy with the C-Flex device may improve overall adherence over 3 months compared to st and ard therapy with CPAP . Clinical outcomes do not improve consistently , but C-Flex users may be more confident about their ability to adhere to treatment . R and omized clinical trials are needed to replicate these findings Expiratory pressure relief ( C-Flex ) technology monitors the patient ’s airflow during expiration and reduces the pressure in response to the patient . Increased comfort levels associated with C-Flex therapy have potential to improve patient adherence to therapy . The purpose of this study was to assess the combination of autoadjusting CPAP ( APAP ) and C-Flex in terms of ( 1 ) treatment efficacy , and ( 2 ) patient preference when compared to st and ard CPAP . Fifteen patients who had previously undergone formal CPAP titration polysomnography were treated with either one night of the APAP with C-Flex or one night of conventional CPAP , in a crossover trial . Patient satisfaction levels were recorded using visual analog scales ( VAS ) on the morning after the study . Mean patient age was 50 ± 12 years , body mass index ( BMI ) was 36 ± 6 kg/m2 , baseline AHI was 53 ± 31 events/h , and CPAP Pressure was 11 ± 2 cm/H2O . APAP with C-Flex was as effective as CPAP , with no differences detected in sleep latency ( 17 ± 5 vs 12.3 ± 3 min , p = 0.4 ) , or respiratory indices ( AHI of 4.2 ± 2 vs 2.4 ± 0.7 events/h , p = 0.1 ) . VAS scores ( scale 0–10 ) indicated a trend towards increased patient satisfaction while using APAP with C-Flex ( 7.9 vs 7.2 , p = 0.07 ) . 10 patients expressed a preference for APAP with C-Flex ( VAS , 0 to10 ) over st and ard CPAP ( total positive score of 68 , mean score of 4.8 ± 4.3 ) . One patient expressed no preference . Four patients expressed a preference for CPAP ( total positive score of 13 , mean score of 0.9 ± 1.9 ) ( APAP with C-Flex vs st and ard CPAP , p < 0.01 paired t test ) . APAP with C-Flex eliminates sleep disordered breathing as effectively as st and ard CPAP . Patients indicated a preference for APAP with C-Flex suggesting a possible advantage in terms of patient adherence for this mode of treatment BACKGROUND The aims of this study were to compare compliance to treatment with fixed CPAP and with autoCPAP , subjective preference for type of CPAP treatment , and factors associated to preference for autoCPAP in patients with OSAS . PATIENTS AND METHODS Twenty-two subjects were studied in a r and omized , single blind cross-over fashion . They were treated for one month by fixed CPAP ( Elite Sullivan V , ResMed , Sydney , Australia ) and one month by autoCPAP ( Autoset T , ResMed , Sydney , Australia ) . RESULTS Four subjects who stated a preference for fixed CPAP and four who expressed no preference were pooled together ; fourteen preferred autoCPAP . Compliance to treatment using the two machines did not differ in the first group ( 3.8 ( 1.9 ) vs. 3.8 (1.5)h/day , fixed vs autoCPAP ) , but was higher with autoCPAP in the second group ( 4.8 ( 1.8 ) vs 5.5 (1.5)h/day , P<0.05 ) . Baseline apnea/hypopnea index ( AHI ) was high in both groups , but was higher in the second group P<0.02 . First treatment was always fixed CPAP in patients who preferred fixed CPAP , while it was either in the other subjects . CONCLUSIONS Compliance to autoCPAP differs among OSAS patients . As long as factors predicting higher compliance to autoCPAP are not found , a trial with autoCPAP in patients poorly compliant to fixed CPAP may be warranted INTRODUCTION Apnea is a common disorder in older adults and has been shown to affect cognition . Some studies suggest that treatment for apnea improves certain cognitive deficits , but few studies have examined the relationship between compliance and cognitive improvement . We design ed a study to answer the following questions about sleep apnea , cognition and treatment in older adults : ( 1 ) Which neuropsychological ( NP ) variables are differentially associated with measures of sleep fragmentation and oxygen desaturation ? ( 2 ) Does compliant use of CPAP provide a cognitive advantage over noncompliant use ? ( 3 ) Does NP performance at baseline predict compliance at 3 months ? METHOD Twelve participants were recruited for the study . All had polysomnographically defined sleep apnea with an RDI of 10 or greater . All were also at least 55 years of age , had no other diagnosable sleep disorder and had no previous treatment for sleep apnea syndrome ( SAS ) . Participants were administered a full NP battery before and 3 months after treatment with CPAP . RDI at baseline was associated with delayed verbal recall , while oxygen desaturation was associated with both delayed recall and constructional abilities . Compliant use of CPAP at 3 months was associated with greater improvements in attention , psychomotor speed , executive functioning and nonverbal delayed recall . Finally , attention measures predicted compliance at 3 months suggesting that those who were least vigilant at baseline were more likely to comply with treatment . DISCUSSION Results are discussed in terms of the relevance to targeting special population s for compliance interventions , the ways that treatment may specifically affect older adults and the possible dose-response relationship of CPAP STUDY OBJECTIVES To determine long-term compliance rates to continuous positive airway pressure ( CPAP ) therapy in patients with obstructive sleep apnea enrolled in a comprehensive CPAP program in the community . DESIGN Prospect i ve cohort longitudinal study . SETTING University sleep disorders center . PATIENTS Two hundred ninety-six patients with an apnea-hypopnea index ( AHI ) > or = 20/h on polysomnography . INTERVENTIONS A CPAP device equipped with a monitoring chip was supplied . Within the first week , daily telephone contacts were made . Patients were seen at 2 weeks , 4 weeks , 3 months , and 6 months . RESULTS Of the 296 subjects enrolled , 81.1 % were males . Mean + /- SD AHI was 64.4 + /- 34.2/h of sleep ; age , 51 + /- 11.7 years ; and body mass index , 35.2 + /- 7.9 kg/m(2 ) . The mean duration of CPAP use was 5.7 h/d at 2 weeks , 5.7 h/d at 4 weeks , 5.9 h/d at 3 months , and 5.8 h/d at 6 months . The percentage of patients using CPAP > or = 3.5 h/d was 89.0 % at 2 weeks , 86.6 % at 4 weeks , 88.6 % at 3 months , and 88.5 % at 6 months . There was a decrease in the Epworth Sleepiness Scale ( ESS ) score of 44 % by 2 weeks of therapy . The patients continue to improve over the follow-up period , with the lowest mean ESS score observed at 6 months . With multiple regression analysis , three variables were found to be significantly correlated with increased CPAP use : female gender , increasing age , and reduction in ESS score . CONCLUSION A population -based CPAP program consisting of consistent follow-up , " troubleshooting , " and regular feedback to both patients and physicians can achieve CPAP compliance rates of > 85 % over 6 months The obstructive sleep apnea syndrome ( OSAS ) is highly prevalent ; it is found in 4 % of middle-aged men and 2 % of middle-aged women [ 1 ] . The increase in the rate of illness and death associated with this disease emphasizes the need for effective treatment [ 2 - 5 ] . Approaches to therapy include weight loss [ 6 ] , upper airway surgery [ 7 ] , oral appliances [ 8 ] , and nasal continuous positive airway pressure ( CPAP ) [ 9 ] . Therapy with CPAP decreases the rate of illness and death associated with sleep apnea [ 5 , 10 , 11 ] . Before CPAP therapy is started at home , a polysomnographic study must be done to determine the pressure needed to resolve apnea , hypopnea , snoring , and respiratory-related arousals in all sleep stages and body positions . The CPAP device is then set to this level . Effective pressure can also be estimated by using a regression model that takes into account anthropometric characteristics , neck circumference , and the frequency of nocturnal breathing abnormalities [ 12 ] . However , the regression model often underestimates the positive pressure requirements . A recent report [ 13 ] suggested that effective pressure can be reliably estimated during unattended sleep studies by using automatic adjustments of the positive pressure made on the basis of a record of respiratory variables . Because the optimal CPAP comprises several factors , the effective pressure can change within one night and from one night to another depending on changes in body position [ 14 , 15 ] , sleep stage [ 14 ] , neck and m and ibular position [ 16 , 17 ] , nasal patency , upper airway edema [ 18 ] , and other factors . This variability has led to the development of automatic CPAP devices that continuously adapt the positive pressure in response to varying needs . We compared the efficacy of conventional CPAP therapy with that of automatic CPAP therapy administered by an automatic CPAP machine ( Morphee Plus , Pierre Medical , Verrieres-Le-Buisson , France ) for OSAS [ 19 ] . With this machine , the user must establish a reference pressure that usually corresponds to the effective pressure determined by a conventional titration sleep study . However , the effective pressure can be estimated by the user 's characteristics ; we hypothesized that the ability of the automatic CPAP machine to automatically adjust the positive pressure should compensate for the uncertainty in effective pressure determination obtained by the regression model . This procedure may provide effective treatment of OSAS without doing a CPAP titration sleep study . We compared the efficacy of automatic CPAP given at an estimated reference pressure , automatic CPAP given at a measured reference pressure , and conventional CPAP therapy . Methods Patients The study was conducted between 30 May 1995 and 16 May 1996 . Thirty-nine patients were asked to participate , but 3 refused to participate because of their work schedules . Therefore , 36 patients ( age range , 36 to 65 years ; mean body mass index SD , 36.4 7.6 kg/m2 ) with previously untreated OSAS were included . All patients were seen at the sleep clinic at Hopital Laval . A diagnosis was made on the basis of clinical features and was confirmed by a polysomnographic study ( mean apnea + hypopnea index [ events per hour ] SD , 43.6 19.8 ) . After this diagnostic study , all patients who chose to be treated with nasal CPAP and had no exclusion criteria were asked to participate in the study . Patients were excluded if they had life-threatening forms of OSAS ( such as severe hypersomnolence ) that required immediate treatment , OSAS associated with nonobstructive sleep-related breathing disorders ( such as periodic breathing and hypoventilation ) or with nonrespiratory sleep disorders ( such as narcolepsy and periodic leg movements ) , or an estimated pressure above 15 cm H2O . Treatment with Continuous Positive Airway Pressure A titration sleep study was conducted within 1 week after the diagnostic sleep study to determine the effective pressure in all patients . Patients were then r and omly assigned to one of three treatment groups in a single-blind fashion . The Morphee Plus automatic CPAP device will soon be distributed in North America by Nellcor Puritan-Bennett ( Eden Prairie , Minneapolis , Minnesota ) under the name of Cloudnine . The device has not yet been approved by the U.S. Food and Drug Administration . Because the Morphee Plus device can be set to a constant or an automatic CPAP mode , we used this machine to treat the three groups . In the automatic CPAP mode , the positive pressure is allowed to change within a determined range around the reference pressure . The reference pressure and the upper and lower pressure thresholds are chosen separately by the physician . Group 1 was treated with conventional CPAP ; that is , a constant pressure was set at the effective pressure . For groups 2 and 3 , the machine was used in the automatic CPAP mode ; the reference pressure was set at the measured effective pressure for group 2 and at the estimated effective pressure for group 3 . The estimated effective pressure was calculated by using the following formula [ 12 ] : ( Equation 1 ) We set the range of pressure at 3 cm H2O above the reference pressure to 4 cm H2O below the reference pressure in accordance with our previous experience with this machine [ 19 ] and the level of underestimation reported with the estimated pressure formula [ 12 ] . Patients were blinded to treatment assignment . For each block of three patients , the treatment regimen was determined by using a r and omization table . To compare patients with similar severity of disease , patients were paired for the estimated pressure value . In each block of three patients , the estimated pressure could not differ by more than 1 cm H2O from the value of the first patient included in that block . If a c and i date did not meet this criterion , he or she was assigned to the first r and omized position in the next block of three patients . Characteristics of Automatic Continuous Positive Airway Pressure In the automatic CPAP mode , the positive pressure is maintained as long as ventilation remains stable ; however , any respiratory disorder results in a progressive increase in the pressure . If a breathing disturbance has not occurred for more than 4 minutes , the positive pressure decreases again . Changes in pressure are regulated by a constant feedback analysis of the patient 's ventilation by the nasal CPAP device . The breath-by-breath difference between maximal inspiratory and expiratory flow is estimated by the changes in compressor speed required to maintain a constant positive pressure throughout the respiratory cycle . Apneic and hypopneic events are associated with a decrease in the difference between the inspiratory and expiratory flow ; this leads to an increase in the pressure until the flow regimen of the compressor has become stable or the fixed upper limit of pressure has been reached . Outcome Measures Sleep and breathing characteristics were measured during polysomnographic studies that consisted of continuous electroencephalography [ C4/A1 , C3/A2 , O2/A1 , and O1/A2 ] , submental electromyography , electrooculography , and electrocardiography and measurement of 1 ) nasobuccal airflow by thermistors , 2 ) thoracoabdominal movements by inductive plethysmography [ Respitrace , Ambulatory Monitoring , Inc. , Arsdley , New York ] , 3 ) arterial oxyhemoglobin saturation ( Sao 2 ) level with an ear oximeter [ 504 Pulse oximeter , Criticare Systems , Inc. , Waukesha , Wisconsin ] , and 4 ) breathing noises by two microphones placed at the bedside . All variables were recorded on a computer ( S and man , Melleville Diagnostics , Ottawa , Ontario , Canada ) . Polysomnographic recordings were manually interpreted in 30-second periods according to established criteria [ 20 ] . Arousals were scored according to the definition established by the American Sleep Disorders Association [ 21 ] . Apnea was defined as the cessation of nasal-oral airflow for at least 10 seconds . Hypopnea was defined as a decrease of more than 50 % in total thoracoabdominal movements for at least 10 seconds and was associated with a 2 % decrease in Sao 2 level or an arousal . Diurnal somnolence was assessed by using the Epworth Sleepiness Scale [ 22 ] and maintenance-of-wakefulness tests [ 23 ] . For the latter , patients were seated in a comfortable armchair every 2 hours and asked to remain awake as long as possible during four consecutive 40-minute periods in darkness . Each maintenance-of-wakefulness test was stopped after 10 minutes of sleep or after 40 minutes if no sleep was recorded ; sleep onset was defined as three continuous periods of stage I sleep , any period of stage II to IV or rapid eye movement sleep . Sleep latency was defined as the mean value of the four tests . The mean positive pressure , the proportion of time spent at different pressures , and the time at which positive pressure was applied were automatically recorded each night by the CPAP device for 3 weeks . Changes in positive pressure were analyzed during the control sleep study by continuous recording of mask pressure . Compliance with CPAP therapy was assessed by measuring the amount of CPAP used during the study period and was quantified by measuring the percentage of time during which the machine was turned on and positive pressure was applied ( effective pressure-time index ) and the number of nights during which positive pressure was applied for more than 4 hours and more than 7 hours [ 24 ] . After 3 weeks of treatment with CPAP , a control sleep study was done by using the CPAP device on the setting that patients had used for the past 3 weeks . The Epworth Sleepiness Scale and maintenance-of-wakefulness tests were completed at baseline and on the day after the third polysomnographic recording . Time and pressure readings were printed from the machine at the end of the study period . Changes in the apnea + hypopnea index and diurnal hypersomnolence after CPAP therapy and differences in compliance with CPAP therapy among the three treatment groups were the main study end points . Background : Untreated , obesity hypoventilation is associated with significant use of health care re sources and high mortality . It remains unclear whether continuous positive airway pressure ( CPAP ) or bilevel ventilatory support ( BVS ) should be used as initial management . The aim of this study was to determine if one form of positive pressure is superior to the other in improving daytime respiratory failure . Methods : A prospect i ve r and omised study was performed in patients with obesity hypoventilation referred with respiratory failure . After exclusion of patients with persisting severe nocturnal hypoxaemia ( Spo2 < 80 % for > 10 min ) or carbon dioxide retention ( > 10 mm Hg ) despite optimal CPAP , the remaining patients were r and omly assigned to receive either CPAP or BVS over a 3-month period . The primary outcome was change in daytime carbon dioxide level . Secondary outcome measures included daytime sleepiness , quality of life , compliance with treatment and psychomotor vigilance testing . Results : Thirty-six patients were r and omised to either home CPAP ( n = 18 ) or BVS ( n = 18 ) . The two groups did not differ significantly at baseline with regard to physiological or clinical characteristics . Following 3 months of treatment , daytime carbon dioxide levels decreased in both groups ( CPAP 6 ( 8) mm Hg ; BVS 7 ( 7 ) mm Hg ) with no between-group differences . There was no difference in compliance between the two treatment groups ( 5.8 ( 2.4 ) h/night CPAP vs 6.1 ( 2.1 ) h/night BVS ) . Although both groups reported an improvement in daytime sleepiness , subjective sleep quality and psychomotor vigilance performance were better with BVS . Conclusions : Both CPAP and BVS appear to be equally effective in improving daytime hypercapnia in a subgroup of patients with obesity hypoventilation syndrome without severe nocturnal hypoxaemia . Trial registration number : Australian Clinical Trials Registry ACTRN01205000096651 Whether computerized autoadjusted continuous positive airway pressure ( aCPAP ) is effective or even superior to constant continuous positive airway pressure ( cCPAP ) in the treatment of obstructive sleep apnea syndrome ( OSAS ) is still controversial . We performed a r and omized , double-blind , controlled , cross-over trial comparing efficacy of sleep apnea home therapy by a novel aCPAP machine ( REMStarAuto ; Respironics ; Murrysville , PA ) operated in autoadjusted or constant mode . Thirty sleep apnea patients were recruited consecutively . Mean baseline Epworth sleepiness scale ( ESS ) score was 12.7 + /- 0.6 ( + /- SD ) , mean sleep resistance time was 26 + /- 2 min ( Osler test ; Stowood Scientific Systems ; Oxford , UK ) , and mean apnea-hypopnea index ( AHI ) was 41.1 + /- 3.6 h. Patients were r and omly assigned to 1 month of home therapy with aCPAP followed by 1 month with cCPAP , or vice versa . After 1 month with treatment , the mean ESS score , sleep resistance time , and AHI were significantly improved ( 6.6 + /- 0.6 , 37 + /- 1 min , and 4.6 + /- 0.7 h , respectively ; all p < 0.05 vs baseline ) . Similar effects were achieved with cCPAP ( p = not significant vs aCPAP ) . Twenty-six patients preferred aCPAP , and 4 patients preferred cCPAP ( p < 0.001 ) . We conclude that patients with OSAS preferred aCPAP over cCPAP in the initial phase of therapy . The effectiveness aCPAP in improving major outcomes was equivalent to cCPAP . Since aCPAP does not require initial titration , it is a simple and promising modality for sleep apnea home therapy STUDY OBJECTIVES To compare in a multicenter prospect i ve study the efficacy and cost of conventional nasal continuous positive airway pressure ( nCPAP ) initiated at the sleep laboratory versus auto-nCPAP initiated at home . DESIGN Patients with severe obstructive sleep apnea syndrome ( OSAS ) were r and omized to treatment with either the REM+ auto device in constant mode at the effective pressure determined by titration at the sleep laboratory ( n=17 ) or the REM+ auto device in automatic mode initiated at the patients home by a nurse ( n=18 ) . After 2 months , the efficacy and cost of nCPAP therapy and the time from diagnosis to nCPAP were evaluated . All values are reported as means + /- SD . PATIENTS Thirty-five subjects with newly diagnosed OSAS ( 8 women and 27 men , mean age : 54.3 + /- 10.6 years , apnea-hypopnea index ( AHI ) 58.1 + /- 14.0 h(-1 ) ) . INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Both treatments were used properly and induced similar decreases in the AHI ( 7.6 + /- 6.9 vs. 10.4 + / -12.5 h(-1 ) for auto-nCPAP and conventional nCPAP , respectively ; NS ) and Epworth Sleepiness score ( from 15.5 + /- 4.7 to 7.5 + /- 3.4 vs. 14.7 + /- 3.9 to 7.6 + /- 3.4 for auto-nCPAP and conventional nCPAP , respectively ; NS ) . With auto-nCPAP initiated at home , the time from diagnosis to final adjustment of nCPAP was shorter ( 16.3 + /- 5.0 vs. 47.2 + /- 46.5 days with conventional nCPAP , P < 0.02 ) and the cost was lower ( 1,263 + /- 352 vs. 1720+/-455 E , respectively ; P < 0.05 ) . CONCLUSIONS Treatment of OSAS with auto-nCPAP initiated at home is effective and reliable and reduces the time from diagnosis to therapy and the cost of treatment This study evaluated the efficacy of behavioral techniques ( i.e. , parent training , modeling , and desensitization ) to facilitate use of nasal continuous positive airway pressure ( CPAP ) in four children with obstructive sleep apnea ( OSA ) secondary to anatomic disorder of the upper airway . All patients tolerated CPAP with training : Polysomnographic data revealed improvement in sleep architecture , apnea , and oxygenation , and patients were discharged on CPAP units . All patients continued to use CPAP throughout the 3-month follow-up period and none required additional treatment for OSA . Three of four patients continued to use CPAP at the 9-month follow-up visit . Treatment result ed in improvements in alertness , attention/concentration , and behavior/temperament . Children generally have been considered poor c and i date s for nasal CPAP , and historically they have been offered instead more invasive procedures . This study suggests that CPAP is a viable treatment for such children when paired with behavioral interventions that facilitate its use Background : Heated humidifiers ( HH ) enable effective treatment of upper airway dryness during nasal continuous positive airway pressure ( nCPAP ) therapy for obstructive sleep apnoea ( OSA ) , but the role of prophylactic use of HH during the initiation of nCPAP treatment has not been studied so far . Objectives : The aim of the present study was to investigate whether prophylactic HH during the initiation of CPAP would result in improved initial patient comfort and acceptance . Methods : In 44 consecutive , previously untreated OSA patients with no history of upper airway dryness , CPAP titration with and without HH was performed on two consecutive nights in a r and omised order . The patients were interviewed after each treatment night in order to establish the comfort of the treatment , and , after the second treatment , they were asked which of the two nights they considered more pleasant , and which treatment they would prefer for long-term use . Results : Following CPAP titration with HH , 32 patients ( 73 % ) cl aim ed to have had a better night ’s sleep than usual ( i.e. without CPAP treatment ) compared with 33 patients ( 75 % ) saying the same following CPAP treatment without HH . For 21 patients ( 47.7 % ) treatment with HH was more pleasant , 23 ( 52.3 % ) saw no difference or said that treatment without HH was more pleasant . Nineteen patients ( 43.2 % ) gave preference to treatment with HH for long-term use , while 25 patients ( 56.8 % ) had no preference or said they would prefer treatment without HH . Conclusions : The use of HH during the initiation phase of CPAP treatment was associated neither with an initial improvement in comfort nor with greater initial treatment acceptance Heated humidification of nasal continuous positive airway pressure ( nCPAP ) reduces upper airway symptoms and improves initial use in obstructive sleep apnoea syndrome ( OSAS ) . The present study aim ed to assess the effect of heated humidification of nCPAP on upper airway symptoms and initial use in obstructive sleep apnoea . This study was of a r and omised , crossover design . Subjects with polysomnographically confirmed OSAS were r and omised to 3 weeks nCPAP treatment with heated humidification ( nCPAP-humid ) or placebo humidification ( nCPAP pl-humid ) . Objective and subjective nCPAP use , upper airway symptoms , and treatment satisfaction were compared . Thirty seven of 42 patients completed the protocol . nCPAP-humid reduced the frequency of adverse upper airway symptoms . nCPAP use over 3 weeks was greater with nCPAP-humid compared with nCPAP pl-humid . No difference was found between the treatment arms in terms of subjective treatment satisfaction or alertness . Heated humidification of nasal continuous positive airway pressure reduces upper airway symptoms and is associated with a small increase in initial use but not subjective sleepiness or treatment satisfaction . The results support the use of heated humidification as a strategy to reduce side-effects related to continuous positive airway pressure but not routine initial use Sleep-disordered breathing is a common disorder with a range of harmful sequelae . Obesity is a strong causal factor for sleep-disordered breathing , and because of the ongoing obesity epidemic , previous estimates of sleep-disordered breathing prevalence require updating . We estimated the prevalence of sleep-disordered breathing in the United States for the periods of 1988 - 1994 and 2007 - 2010 using data from the Wisconsin Sleep Cohort Study , an ongoing community-based study that was established in 1988 with participants r and omly selected from an employed population of Wisconsin adults . A total of 1,520 participants who were 30 - 70 years of age had baseline polysomnography studies to assess the presence of sleep-disordered breathing . Participants were invited for repeat studies at 4-year intervals . The prevalence of sleep-disordered breathing was modeled as a function of age , sex , and body mass index , and estimates were extrapolated to US body mass index distributions estimated using data from the National Health and Nutrition Examination Survey . The current prevalence estimates of moderate to severe sleep-disordered breathing ( apnea-hypopnea index , measured as events/hour , ≥15 ) are 10 % ( 95 % confidence interval ( CI ) : 7 , 12 ) among 30 - 49-year-old men ; 17 % ( 95 % CI : 15 , 21 ) among 50 - 70-year-old men ; 3 % ( 95 % CI : 2 , 4 ) among 30 - 49-year-old women ; and 9 % ( 95 % CI : 7 , 11 ) among 50 - 70 year-old women . These estimated prevalence rates represent substantial increases over the last 2 decades ( relative increases of between 14 % and 55 % depending on the subgroup ) STUDY OBJECTIVES To evaluate the effects of humidification on nasal symptoms and compliance in sleep apnea patients using continuous positive airway pressure ( CPAP ) . DESIGN A r and omized , crossover design was employed . SETTING The study was conducted at two suburban community-based hospital sleep laboratories . PATIENTS Data were collected on 38 obstructive sleep apnea patients ( mean age , 44.1 years ) in whom CPAP was a novel treatment . INTERVENTIONS The interventions were heated humidity , cold passover humidity , and a washout period without humidity . MEASUREMENTS AND RESULTS Patients were titrated with heated humidity or cold passover humidity in the laboratory and subsequently initiated on humidity . Objective compliance , self-report of factors affecting CPAP use , satisfaction with CPAP , feeling upon awakening , and daytime sleepiness were assessed at the completion of each 3-week treatment period and a 2-week washout period . Outcome measures were assessed with one-way analysis of variance followed by Scheffe post hoc comparisons . Significant main effects were observed for compliance ( F2,37 = 5.2 ; p = 0.008 ) , satisfaction with CPAP ( F2,37 = 4.5 ; p = 0.01 ) , and feeling refreshed on awakening ( F2,37 = 4.4 ; p = 0.02 ) . A significant decrease in daytime sleepiness was observed between baseline and each of the conditions ( F3,37 = 55.5 ; p<0.0001 ) , but Epworth sleepiness scale scores did not differ between conditions ( all p values > 0.56 ) . CPAP use with heated humidity ( 5.52+/-2.1 h/night ) was greater than CPAP use without humidity ( 4.93+/-2.2 h/night ; p = 0.008 ) . Compliance differences were not observed between CPAP use with cold passover humidity and CPAP use without humidity . Patients were more satisfied with CPAP when it was used with heated or cold passover humidity ( p < or = 0.05 ) . However , only heated humidity result ed in feeling more refreshed on awakening ( p<0.05 ) . No significant differences were observed among the three groups on the global adverse side effect score ( F2,37 = 2.5 ; p = 0.09 ) . Specific side effects such as dry mouth or throat and dry nose were reported less frequently when CPAP was used with heated humidity compared to CPAP use without humidity ( p<0.001 ) . CONCLUSIONS Compliance with CPAP is enhanced when heated humidification is employed . This is likely due to a reduction in side effects associated with upper airway symptoms and a more refreshed feeling upon awakening . Compliance gains may be realized sooner if patients are started with heated humidity at CPAP initiation STUDY OBJECTIVES Autoadjustable continuous positive airway pressure ( CPAP ) devices are increasingly used in the treatment of obstructive sleep apnea ( OSA ) . Since different measurements of upper airway obstruction are applied , it is uncertain whether these devices are equally effective in controlling sleep-disordered breathing . Hypothesizing that differences in therapeutic efficacy were to come out , we compared the performance of the AutoSet device ( ResMed ; Sydney , Australia ) , which features autoadjustable positive airway pressure ( APAP ) guided by detection of flow limitation ( APAPfl ) , with the SOMNOsmart device ( Weinmann ; Hamburg , Germany ) , which features APAP guided by the forced oscillation technique ( APAPfot ) . DESIGN A double-blind , r and omized , cross-over trial . SETTING The sleep disorders center and sleep laboratory of a university hospital . PATIENTS AND INTERVENTIONS An overnight CPAP autotitration procedure was performed in 30 patients with OSA . A split-night protocol allowed that each patient used both devices . MEASUREMENTS AND RESULTS Using polysomnography , sleep , indexes of sleep-disordered breathing , snoring , and CPAP levels were recorded . No significant differences were found in conventional sleep variables . While the apnea-hypopnea index ( AHI ) was lower with APAPfl ( 3.5 + /- 5.6/h ) as compared to APAPfot ( 9.9 + /- 31.0/h ) , the difference was not statistically significant ( mean + /- SD ) . The snoring index , however , was significantly lower with APAPfl ( 35.3 + /- 53.7/h vs 111.6 + /- 175.4/h , respectively ; p = 0.01 ) . The median and 95th percentile pressure levels rose from wakefulness to sleep in APAPfl , but decreased in APAPfot . Higher pressure variability was present in the latter method . CONCLUSIONS These findings suggest that the APAPfl is superior to APAPfot in the control of snoring . While a lower AHI was achieved with APAPfl , at the expense of a higher median pressure but less pressure variability , the difference with APAPfot was not statistically significant Auto-adjustable continuous positive airway pressure ( APAP ) devices are an emerging treatment alternative to fixed-pressure continuous positive airway pressure ( CPAP ) therapy for obstructive sleep apnoea syndrome . They have been engineered to automatically adjust the pressure to the optimal level on a continuous basis . However , not all APAP technologies use the same algorithm . Three different APAP devices ( Autoset Spirit , Breas PV 10i and RemStar Auto ) were compared in a r and omised crossover trial in patients already established on fixed-pressure CPAP therapy . The outcome measures were compliance , quality of life and side-effects . Twenty-seven middle-aged patients ( 25 male ) previously diagnosed with severe obstructive sleep apnoea syndrome ( median ( interquartile range ) apnoea/hypopnoea index 48 ( 29–76 ) ) , established on CPAP therapy for > 3 yrs , were r and omised to each APAP device for 4 weeks . Mean pressure and patient compliance were significantly lower on the Breas PV 10i than on the other APAP devices . The devices were similar in terms of quality of life , daytime sleepiness and upper airway side-effects , but patients evaluated them significantly differently in terms of device features , sleep quality and pressure comfort , with the Breas PV 10i being the least popular . Auto-adjustable positive airway pressure devices differ in pressure delivery and patient compliance in obstructive sleep apnoea syndrome patients We evaluated the efficiency of two different treatment procedures with continuous positive airway pressure ( CPAP ) on sleep , nocturnal breathing characteristics and daytime vigilance in 18 newly diagnosed patients with untreated sleep apnoea/hypopnoea syndrome ( SAHS ) r and omly allocated to two different groups . In group I , the positive pressure ( PP ) level was set to suppress flow limitation ( PFL ) , while in group II the PP was set at a level that eliminated only apnoea/hypopnoea and snoring ( PAHS ) . At the end of a 3 week period of home CPAP therapy , a follow-up sleep study , vigilance and cognitive tests were made . Overall , PFL was significantly higher than PAHS values ( PFL : 10.42.6 cmH2O ; PAHS : 8.9+/-2.6 cmH2O ; p<0.01 , mean+/-SD ) . We found no difference in sleep quality , nocturnal saturation and apnoea/hypopnoea index , or in daytime vigilance tests between the two groups at the end of the treatment period . However , there was a significantly greater scattering in the changes of sleep latency in group II than in group I. This was associated with a significant difference in the daily duration of nasal CPAP use between the two groups ( group I : 7.29+/-0.95 h x day(-1 ) ; group II : 6.01+/-0.94 h x day(-1 ) ; p=0.01 ) and with a positive correlation between final maintenance of wakefulness test values and the duration of CPAP use ( p<0.05 ; r=0.55 ) . These results tend to show that correcting flow limitation is associated with a higher observance and a more important efficiency in normalizing daytime vigilance than with conventional nasal continuous positive airway pressure Continuous positive airway pressure ( CPAP ) is an effective treatment for obstructive sleep apnoea syndrom ( OSAS ) but therapy adherence is often low . The hypothesis that CPAP-adherence and clinical outcomes can be improved by either using an autoadjusting-CPAP ( APAP ) device or an intensive support was tested . A controlled parallel group study was performed with 100 newly diagnosed OSAS patients , r and omised into 4 groups ( n = 25 each ) : st and ard or intensive support plus either APAP or CPAP . Intensive support included education and monthly home visits for 6 months . Clinical outcome was monitored by polysomnography at CPAP initiation and , after 3 and 9 months , compliance data were downloaded from the CPAP devices . After 9 months , intensively supported patients returned for follow-up in 88 versus 68 % in the st and ard-support-group . Daily usage ( mean±sem 5.7±0.2 for intensive support versus 4.6±0.4 h for st and ard support ) , percentage of days used ( 80.4±2.8 versus 57.0±5.9 % ) and proportion of individual sleep time ( 80.6±3.2 versus 64.9±6.2 % ) were also higher . There was no significant difference between APAP or CPAP , ( daily usage 5.2±0.4 versus 5.1±0.3 h , percentage of days 67.9±5.0 versus 69.2±4.9 % , proportion of sleep time 72.5±5.0 % versus 72.1±5.2 % , for APAP and CPAP ) but retention rate was higher with CPAP . In summary , intensive support after continuous positive airway pressure initiation , rather than the application of autoadjusting-continuous positive airway pressure , increased therapy adherence The forced oscillation technique ( FOT ) has been demonstrated to be a very sensitive tool for the assessment of upper airway obstruction during nasal continuous positive airway pressure ( CPAP ) therapy for obstructive sleep apnoea ( OSA ) . The present study was design ed to evaluate the therapeutic efficacy of a novel auto-CPAP device based exclusively on the FOT . Following manual CPAP titration , 18 patients with OSA ( mean apnoea/hypopnoea index ( AHI ) 48.0+/-28.1 ) were allocated to conventional CPAP and auto-CPAP treatment under polysomnographic control in r and omized order . The patients were asked to assess their subjective daytime sleepiness using the Epworth Sleepiness Scale ( ESS ) . The mean AHI during auto-CPAP treatment was 3.4+/-3.4 and was comparable with that obtained during conventional CPAP treatment ( 4.2+/-3.6 ) . The analysis of sleep architecture , the arousal index ( 6.6+/-2.1 versus 7.3+/-4.4 ) or the ESS ( 5.6+/-1.8 versus 7.3+/-4.4 ) did not reveal any significant differences . However , the mean CPAP pressure during auto-CPAP treatment ( 0.84+/-0.26 kPa ) and in particular the pressure applied in the lateral body position ( 0.74+/-0.35 kPa ) , was significantly lower than that employed in conventional CPAP treatment ( 0.93+/-0.16 kPa , both comparisons : p<0.05 ) . The auto-continuous positive airway pressure device proved equally as effective as conventional continuous positive airway pressure . However , the mean treatment pressure was significantly reduced , especially when patients were sleeping in the lateral position Nasal symptoms associated with the use of nasal continuous positive airway pressure ( nCPAP ) in obstructive sleep apnoea ( OSA ) can adversely impact on patients ' tolerance , acceptance and adherence to nCPAP therapy . Regular use of heated humidification is effective in alleviating these symptoms and improve patient comfort . In a r and omised , parallel , double-blinded , controlled study , the present authors examined the use of heated humidification during a single night laboratory nCPAP titration in untreated OSA patients and its effect on nasal symptoms , nasal airway resistance ( NAR ) , effective pressure and treatment tolerability and acceptance . Baseline characteristics of subjects ( n = 70 ) receiving placebo and humidification were ( mean±sem ) : age 51.2±2.2 versus 50.6±1.6 yrs ; body mass index 33.6±0.9 versus 35.2±0.9 kg·m−2 ; Epworth Sleepiness Scale 10.8±1.0 versus 11.3±0.7 ; and apnoea-hypopnoea index 43.5±4.6 versus 44.4±4.1 events·h−1 . Total inspiratory NAR , before ( 0.36±0.09 ( placebo ) versus 0.33±0.09 kPa·L−1·s−1 ) and after nCPAP ( 0.47±0.11 versus 0.29±0.04 kPa·L−1·s−1 ) were not significantly different between the groups . No difference was found in the frequency and severity of nasopharyngeal symptoms , therapeutic pressure and subjective response to nCPAP . In conclusion , heated humidification during the initial nasal continuous positive airway pressure titration offers no additional benefit in nasal physiology , symptoms or subjective response to nasal continuous positive airway pressure , and , therefore , should not be routinely recommended Background : Long-term compliance is suboptimal in the treatment of the obstructive sleep apnea syndrome ( OSAS ) . Objectives : We compared the efficacy of and the adherence to automatic continuous positive airway pressure ( APAP ) and constant continuous positive airway pressure ( CPAP ) based on a night-by-night analysis . Methods : We performed a r and omized , single-blind crossover study in 20 patients with moderate-to-severe OSAS . After diagnostic polysomnography and manual titration , patients were treated for 8 weeks with both constant CPAP and APAP in r and om order . Compliance and leakage were analyzed night by night using the software LOGSoft ® of the Magellan ® iPAP device . Results : The reduction in the apnea/hypopnea index ( baseline 32.9 ± 19.1/h , CPAP 4.6 ± 2.9/h , APAP 5.6 ± 3.6/h ; p < 0.001 compared to baseline ) and the Epworth Sleepiness Scale ( baseline 10.3 ± 5.7 , CPAP 6.6 ± 4.8 , APAP 4.9 ± 4.6 ; p < 0.001 compared to baseline ) did not significantly differ between the treatment modes . Leakage time and compliance per night were not statistically different ( leakage CPAP 31 ± 57 min , APAP 25 ± 49 min ; compliance CPAP 383 ± 116 min , APAP 382 ± 107 min ) . There was no correlation between leakage and compliance . Thirteen patients ( 65 % ) preferred APAP at the end of the study . Conclusions : Treatment efficacy and adherence are similar with CPAP and APAP . There is a trend towards lower leakage with APAP therapy . Patients prefer the automatic mode to fixed pressure BACKGROUND Continuous positive airway pressure ( CPAP ) with fixed mask pressure is the current st and ard treatment for obstructive sleep apnoea ( OSA ) . Auto-CPAP devices apply at any time the minimally required pressure to normalise breathing and may improve patient comfort and compliance . We present an open descriptive study of auto-CPAP treatment at home in patients previously managed with conventional CPAP . METHODS Fifteen patients with obstructive sleep apnoea ( OSA ) , previously treated for at least one year with st and ard CPAP , were followed prospect ively for a two month period on auto-CPAP . Outcome measures were both subjective evaluation by the patients and objective ( polysomnographic ) data obtained at one and two months of follow up . RESULTS The Epworth sleepiness score did not change significantly between baseline and follow up after one and two months and no systematic changes in CPAP related side effects were reported . Compared with the baseline polysomnographic values without treatment , a significant improvement in both respiratory and sleep parameters was observed during auto-CPAP . These results were not significantly different from those obtained with st and ard CPAP . A significant correlation was found between the effective CPAP pressure ( Peff ) and the amount of time spent below Peff during auto-CPAP treatment ( r = 0.6 , p = 0.01 ) . CONCLUSION Long term auto-CPAP treatment in these patients with severe OSA appears to provide comparable efficacy to that of st and ard CPAP treatment Background The impact of treating OSA on renal function decline is controversial . Previous studies usually included small sample s and did not consider specific effects of different CPAP modalities . The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate ( eGFR ) in a large sample of patients derived from the prospect i ve European Sleep Apnea Data base cohort . Methods In patients of the European Sleep Apnea Data base , eGFR prior to and after follow‐up was calculated by using the Chronic Kidney Disease‐Epidemiology Collaboration equation . Three study groups were investigated : untreated patients ( n = 144 ) , patients receiving fixed CPAP ( fCPAP ) ( n = 1,178 ) , and patients on autoadjusting CPAP ( APAP ) ( n = 485 ) . Results In the whole sample , eGFR decreased over time . The rate of eGFR decline was significantly higher in the subgroup with eGFR above median ( 91.42 mL/min/1.73 m2 ) at baseline ( P < .0001 for effect of baseline eGFR ) . This decline was attenuated or absent ( P < .0001 for effect of treatment ) in the subgroup of patients with OSA treated by using fCPAP . A follow‐up duration exceeding the median ( 541 days ) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group ( P < .0001 by two‐way ANOVA for interaction between treatment and follow‐up length ) . In multiple regression analysis , eGFR decline was accentuated by advanced age , female sex , cardiac failure , higher baseline eGFR , and longer follow‐up duration , whereas there was a protective effect of fCPAP . Conclusions fCPAP but not APAP may prevent eGFR decline in OSA Background : Heated breathing tubes were developed to improve heated humidification in continuous positive airway pressure ( CPAP ) therapy of patients with obstructive sleep apnea syndrome ( OSAS ) . Objectives : We wanted to investigate the influence of a heated breathing tube on patients ' satisfaction with the treatment , the rate of side effects and the adherence to treatment . Methods : Eighty-eight patients with primarily diagnosed OSAS were treated in a r and omized , controlled , single-blind trial for 12 months either with a CPAP system plus conventional heated humidifier or with a CPAP system plus heated humidifier and an integrated heated breathing tube . Results : Both systems improved the respiratory disturbances and the quality of sleep in a similar manner . The difference in the overall satisfaction with the treatment ( subscale 3 of the visual analogue scale ) between the two treatment groups was not statistically significant ( mean difference -14.1 , 95 % CI -28.7 to 0.6 ; p = 0.059 ) . The rate of side effects and the quality of life did not differ significantly between the two groups . The patients with the heated breathing tube used the treatment on average 1 h longer , but this was not statistically significant ( 4.96 ± 1.95 vs. 3.90 ± 2.54 h/night ; p = 0.06 ) . Conclusions : Controlled heated breathing tube humidification as compared to conventional heated humidification improves neither the adherence to treatment , nor the rate of side effects , nor the quality of life in nonselected OSAS patients OBJECTIVE To assess continuous positive airway pressure ( CPAP ) compliance and factors associated with CPAP compliance among Chinese patients with obstructive sleep apnea ( OSA ) . DESIGN A prospect i ve study of 112 consecutive patients with newly diagnosed OSA commencing CPAP treatment . SETTING A university teaching hospital . MEASUREMENTS AND RESULTS The following factors were evaluated for any correlation with objective CPAP compliance ( effective mask pressure [ hours per day ] ) at 1 month and 3 months : age , baseline apnea-hypopnea index ( AHI ) , common OSA symptoms , minimum arterial oxygen saturation ( SaO(2 ) ) , mean SaO(2 ) , arousal index ( AI ) , Epworth sleepiness scale ( ESS ) , education level , CPAP levels , satisfaction with CPAP , side effects , and machine cost . There were 101 male and 11 female patients , with a mean ( + /- SD ) age of 45.6 + /- 1.2 years ; body mass index , 29.3 + /- 5.2 kg/m(2 ) ; AI , 60 + /- 18/h ; AHI , 48 + /- 24/h ; minimum SaO(2 ) of 70 + /- 17 % ; and mean SaO(2 ) of 86 + /- 7 % . ESS fell from 12.9 + /- 4.0 ( baseline ) to 5.2 + /- 4.7 at 3 months ( p < 0.001 ) . Objective CPAP compliance was 5.4 + /- 1.6 h/d and 5.3 + /- 1.6 h/d , while 75 % and 72 % of our patients were using CPAP objective ly for > or = 4 h/d and at least 70 % of the nights per week at 1 month and 3 months , respectively . Following univariate analysis of variance , a high baseline AHI ( p = 0.006 and p = 0.004 ) was associated with higher objective CPAP compliance at 1 month and 3 months , respectively . CONCLUSION CPAP usage and compliance were high in this patient population . A high baseline AHI was the only significant independent predictor of better CPAP compliance Upper airway dryness is a frequent side-effect of nasal continuous positive airway pressure ( nCPAP ) therapy in obstructive sleep apnoea ( OSA ) . In this situation , heated humidification is often used . Alternatively , oily nose drops are frequently applied to relieve dryness . The present study aim ed to investigate the efficacy of a heated humidifier in comparison with oily nose drops . Twenty-four OSA patients complaining of serious nCPAP-related upper airway dryness were r and omized to 6 weeks of treatment either with heated humidification ( HC 100 , Fischer & Paykel , Inc. , Auckl and , New Zeal and ) or oily nose drops ( Colda-Stop , Desitin , Inc. , Germany ) . The patients completed question naires on the degree and frequency of upper airway dryness , compliance with nCPAP , intention to terminate nCPAP and comfort during the nCPAP therapy . All 12 patients treated with heated humidification improved in terms of the degree and frequency of upper airway dryness , and reported greater comfort when using the nCPAP device . All patients in the heated humidification group intending to terminate nCPAP therapy because of upper airway dryness persisted with nCPAP on addition of humidification . In contrast , only five out of 12 patients ( 42 % ) in the oily nose drops group reported their degree of upper airway dryness to be improved ( P = 0.003 ) , only three patients ( 25 % ) reported an improvement in the frequency of upper airway dryness ( P < 0.001 ) , and only five patients ( 42 % ) reported greater comfort when using the nCPAP device with oily nose drops ( P < 0.001 ) . In the group using oily nose drops none of the three patients who intended to terminate nCPAP therapy persisted with nCPAP . Heated humidification is highly effective and superior to oily nose drops in reducing the symptoms of upper airway dryness during nCPAP BACKGROUND Nasal side effects are common in patients with obstructive sleep apnea syndrome ( OSAS ) starting on nasal continuous positive airway pressure ( CPAP ) therapy . We tested the hypothesis that heated humidification or nasal topical steroids improve compliance , nasal side effects and quality of life in this patient group . METHODS 125 patients with the established diagnosis of OSAS ( apnea/hypopnea index > or = 10/h ) , who tolerated CPAP via a nasal mask , and who had a successful CPAP titration were r and omized to 4 weeks of dry CPAP , humidified CPAP or CPAP with additional topical nasal steroid application ( fluticasone , GlaxoWellcome ) . Groups were similar in all demographic variables and in frequency of nasal symptoms at baseline . Outcome measures were objective compliance , quality of life ( short form 36 ) , subjective sleepiness ( Epworth Sleepiness Scale score ) and nasal symptoms such as runny , dry or blocked nose , sneezing and headaches ; all variables assessed using a vali date d question naire and by direct interview . RESULTS There was no difference in compliance between groups after 4 weeks ( dry : 5.21 + /- 1.66 h/night , fluticasone : 5.66 + /- 1.68 , humidifier : 5.21 + /- 1.84 ; p = 0.444 ) . Quality of life and subjective sleepiness improved in all groups , but there were no differences in the extent of improvement . Nasal Symptoms were less frequently reported in the humidifier group ( 28 % ) than in the remaining groups ( dry : 70 % , fluticasone : 53 % , p = 0.002 ) . However , the addition of fluticasone result ed in increased frequency of sneezing . CONCLUSION The addition of a humidifier , but not nasal steroids decreases the frequency of nasal symptoms in unselected OSAS patients initiating CPAP therapy ; however compliance and quality of life remain unaltered Purpose The objective of this study was to evaluate whether a new auto-adjusting bi-level algorithm was comparable to a st and ard method for prescribing bi-level therapy . Methods This study was a prospect i ve r and omized , double-blinded crossover evaluation of the equivalency of the auto-adjusting bi-level mode ( VAuto ™ ) compared to st and ard bi-level mode , using a pre-determined difference in Apnea – Hypopnea Index ( AHI ) of five events per hour . Data were obtained during sleep studies performed on two separate nights . Twenty-two subjects met the entry criteria and were enrolled in the study at four investigational sites in the USA . Results Mean AHI for the auto-adjusting bi-level mode was 6.2 ± 5.4 events per hour and for the st and ard bi-level mode 8.3 ± 5.8 events per hour . The AHI for the two modes were clinical ly equivalent . The difference in median pressure between these two modes was −3.8 cm H2O ± 3.6 ( p = 0.0008 ) in favor of the auto-adjusting bi-level mode . In addition , the maximum pressure was significantly higher in the auto-adjusting bi-level mode ( 16.0 cm H2O vs. 14.1 cm H2O , p = 0.02 ) . Conclusions Our results demonstrated that the auto-adjusting bi-level mode normalized AHI comparable to the st and ard bi-level mode . The results of this study have several significant implication s for the clinical management of sleep apnea . Obstructive sleep apnea ( OSA ) is a common condition and is associated with untoward complications . Non-compliance with positive airway pressure ( PAP ) limits the efficacy of the PAP therapy . The auto-adjusting bi-level mode provides a potentially reliable alternative for sleep clinicians faced with prescribing bi-level PAP for non-compliant patients . This study documents that this type of auto-adjusting device provides effective treatment of OSA STUDY OBJECTIVE Automatic titration using the forced oscillation technique ( FOT ) has recently been developed for the treatment of obstructive sleep apnea syndrome ( OSAS ) . So far , it is not known if therapy with automatic nasal continuous positive airway pressure ( nCPAP ) using a preset upper pressure limitation or a free range ( which might lead to higher mean pressure ) is preferable with regard to obstructive events , sleep stages , and pressure characteristics . DESIGN After diagnostic polysomnography , patients were r and omly assigned to two setting s with the self-adjusting nCPAP ( APAP ) device based on the FOT . In mode 1 , the pressure variation ranged from 4 to 15.5 cm H(2)O , and in mode 2 , the pressure variation ranged from 4 cm H(2)O to an individual upper pressure limit . PATIENTS Eleven men , aged 53.0 + /- 6.8 years with a body mass index of 32.4 + /- 5.1 kg/m(2 ) and an apnea-hypopnea index ( AHI ) of 31.6 + /- 26.6/h . MEASUREMENTS AND RESULTS Manually titrated pressure was at 9.3 + /- 2.1 cm H(2)O , the mean pressure in mode 1 was 5.4 + /- 1.0 cm H(2)O ( p < 0.01 ) , and the mean pressure in mode 2 was 5.1 + /- 0.7 cm H(2)O ( p < 0.01 ) . A reduction of respiratory events ( baseline AHI , 31.6 + /- 26.6/h ; AHI in mode 1 , 3.4 + /- 4.5 ; AHI in mode 2 , 5.0 + /- 7.2 ; each with p < 0.001 ) and an increase in the " rapid eye movement " stage of sleep ( baseline , 13.0 + /- 5.5 % ; mode 1 , 22.0 + /- 7.7 [ p < 0 . 05 ] ; mode 2 , 23.0 + /- 7.9 [ p < 0.01 ] ) were achieved . In mode 1 , the mean pressure was below the manual pressure 91.7 + /- 9.3 % of the time , and in mode 2 , the mean pressure was below the manual pressure 90.4 + /- 6.3 % of the time . The manual pressure was exceeded by 5.5 + /- 7.4 % ( mode 1 ) and by 5.2 + /- 3.1 % ( mode 2 ) . CONCLUSION We conclude that nCPAP therapy based on the FOT permits the adequate treatment of OSAS with significantly lower pressure than manually titrated nCPAP therapy does . A pre setting of an upper pressure limit has no advantage compared to free range OBJECTIVES To compare polysomnographic data and compliance in sleep apnea patients receiving continuous positive airway pressure ( CPAP ) and pressure-relief CPAP ( PRCPAP ) [ C-flex ; Respironics ; Murrysville , PA ] as first treatment in the sleep laboratory and subsequently at home . DESIGN A prospect i ve , r and omized , crossover design was used in the sleep laboratory , and a prospect i ve r and omized design was used at home . PATIENTS Data were collected from 52 sleep apnea patients for whom CPAP was used for the first time . INTERVENTIONS Treatment with constant CPAP and PRCPAP . MEASUREMENTS AND RESULTS Patients with a first-time diagnosis of obstructive sleep apnea syndrome ( OSAS ) underwent conventional CPAP titration . Thereafter , polysomnography was performed at the titrated pressure using both the fixed CPAP pressure mode and the PRCPAP mode in a r and omized crossover approach . The patients were then discharged home for 7 weeks of treatment with the last-applied treatment mode , and compliance data were established at the end of that time . The average apnea-hypopnea index was 53.3/h in the " diagnostic night , " 5.8/h with CPAP , and 7.0/h with PRCPAP . The native arousal index was 35.2/h , 12.6/h with CPAP , and 12.9/h with PRCPAP ( not significant [ NS ] ) . The central apnea index was 0.7/h with CPAP and 1.2/h with PRCPAP ( p < 0.05 ) . Compliance after 7 weeks was , on average , 9.4 min longer with PRCPAP than with CPAP ( NS ) . Evaluation of a 13-item question naire showed scores of 16.4 for PRCPAP and 18.1 for constant CPAP ( NS ) [ the fewer the complaints , the lower the score ] . With regard to oral dryness , the score with PRCPAP ( 1.4 ) was significantly lower than with constant CPAP ( 1.9 ) [ p < 0.05 ] . This difference was no longer detectable after 7 weeks . CONCLUSION In terms of the effectiveness in treating obstructive sleep apnea , PRCPAP and constant CPAP are comparable . During the first night of treatment , patients receiving PRCPAP had less dryness of mouth ; over a period of 7 weeks , this difference disappeared . Nightly use of the device was comparable in both groups . PRCPAP is therefore a new ventilation mode that enables effective treatment of OSAS patients . Further studies should be done to investigate the effects of expiratory pressure lowering in low-compliance patients and patients requiring CPAP > 9 cm H(2)O or experiencing dry mouth with CPAP Background Millions of individuals with obstructive sleep apnoea ( OSA ) are treated by CPAP aim ed at reducing blood pressure ( BP ) and thus cardiovascular risk . However , evidence is scarce concerning the impact of different CPAP modalities on BP evolution . Methods This double-blind , r and omised clinical trial of parallel groups of patients with OSA indicated for CPAP treatment compared the efficacy of fixed-pressure CPAP ( FP-CPAP ) with auto-adjusting CPAP ( AutoCPAP ) in reducing BP . The primary endpoint was the change in office systolic BP after 4 months . Secondary endpoints included 24 h BP measurements . Results Patients ( 322 ) were r and omised to FP-CPAP ( n=161 ) or AutoCPAP ( n=161 ) . The mean apnoea+hypopnoea index ( AHI ) was 43/h ( SD , 21 ) ; mean age was 57 ( SD , 11 ) , with 70 % of males ; mean body mass index was 31.3 kg/m2 ( SD , 6.6 ) and median device use was 5.1 h/night . In the intention-to-treat analysis , office systolic blood pressure decreased by 2.2 mm Hg ( 95 % CI −5.8 to 1.4 ) and 0.4 mm Hg ( −4.3 to 3.4 ) in the FP-CPAP and AutoCPAP group , respectively ( group difference : −1.3 mm Hg ( 95 % CI −4.1 to 1.5 ) ; p=0.37 , adjusted for baseline BP values ) . 24 h diastolic BP ( DBP ) decreased by 1.7 mm Hg ( 95 % CI −3.9 to 0.5 ) and 0.5 mm Hg ( 95 % CI −2.3 to 1.3 ) in the FP-CPAP and AutoCPAP group , respectively ( group difference : −1.4 mm Hg ( 95 % CI −2.7 to −0.01 ) ; p=0.048 , adjusted for baseline BP values ) . Conclusions The result was negative regarding the primary outcome of office BP , while FP-CPAP was more effective in reducing 24 h DBP ( a secondary outcome ) . Trial registration number NCT01090297 STUDY OBJECTIVES We hypothesized that early intervention with an auto bilevel device would improve treatment adherence compared to CPAP among OSA patients with a poor initial experience with lab-based CPAP titration . METHODS Patients with a poor initial CPAP experience were recruited for this parallel group , r and omized , double-blind , controlled pilot study . After an in-lab titration , patients were r and omized with either an auto-bilevel device or CPAP . Treatment adherence and functioning were assessed at 90 days . RESULTS We enrolled 51 subjects , with 47 completing the protocol . Groups were equally matched for gender , age , education , and OSA severity . There was no significant difference in the proportion of compliant subjects ( ≥ 4 h/night ) between the auto bilevel and CPAP groups ( 62 % vs. 54 % ; p = 0.624 ) after 90 days of use . Functional outcomes significantly improved in both groups during treatment use ( p < 0.001 ) but did not differ between groups . CONCLUSIONS There was no statistically significant difference in adherence between the auto bilevel and CPAP groups in this study . Patients with a poor initial CPAP exposure may still achieve an acceptable long-term clinical outcome . Both groups demonstrated comparably significant improvements in functional outcomes , sleepiness , and fatigue complaints over the treatment period . CLINICAL TRIALS INFORMATION : NCT00635206 Clinical Background : Expiratory pressure relief continuous positive airway pressure ( pressure relief CPAP ; C-Flex ™ ) causes increases in inspiratory duty cycle and shortening of expiratory time . It has been suggested that these changes are caused by an increase in work of breathing . Objectives : We studied the effects of C-Flex on work of breathing and intrinsic positive end-expiratory pressure as compared to fixed CPAP . Methods : Work of breathing was analyzed in 24 patients with obstructive sleep apnea during treatment with fixed CPAP and C-Flex with 3 different pressure relief setting s in a r and omized order during rapid-eye-movement ( REM ) and non-REM sleep . Work of breathing was assessed on a breath-by-breath basis using a piezoelectric esophageal pressure catheter and a pneumotachograph for measuring airflow . Results : We found there was no increase in inspiratory work of breathing observed using C-Flex compared to fixed CPAP . Instead , we found a linear decrease in inspiratory work of breathing with increasing pressure relief , with a mean difference of 1.22 J/min between CPAP and maximum pressure release ( C-Flex 3 ; 90 % of the value with nasal CPAP ) ; however , the decrease was not statistically significant . The decrease in inspiratory work of breathing associated with C-Flex has a significant inverse correlation with BMI . Conclusions : The C-Flex technology does not change work of breathing but shows a tendency towards a reduction of inspiratory work of breathing in patients with a lower BMI using higher C-Flex . The effect is probably caused by diminishing airway resistance generated by the positive end-expiratory pressure . Our findings may lead to additional fields of application of the C-Flex technology , such as chronic obstructive pulmonary disease or muscular dystrophy STUDY OBJECTIVES Auto-continuous positive airway pressure ( CPAP ) has been reported to have no more efficacy than constant CPAP in unselected patients with sleep apnea hypopnea syndrome ( SAHS ) . The aim of this study was to evaluate patients judged to be good c and i date s for auto-CPAP because of a high within-night variability in pressure requirement . DESIGN Single-blind , r and omized , cross-over study ( 2 x 8 weeks ) to compare auto-CPAP with constant CPAP . PATIENTS Out patients with moderate-to-severe SAHS attending the chest clinic . INTERVENTIONS Patients were equipped at home in the auto-CPAP mode ( model GK418A ; Malinckrodt ; Nancy , France ) , using a 4- to 14-cm H(2)O pressure range . Those individuals having a high within-night variability in pressure requirement , assessed at the end of a 14-day run-in period , were included in the cross-over study . Auto-CPAP was compared with constant CPAP ( according to a titration night in the sleep laboratory ) in terms of compliance , efficacy on apneas ( assessed from the pressure monitor ) , and sleepiness ( assessed on the Epworth sleepiness scale ) . MEASUREMENTS AND RESULTS Of 90 consecutive patients with SAHS , 27 patients were selected for a within-night variability in pressure requirement exceeding a given threshold . After completion of the cross-over , 24 patients were evaluable . The median percentage of nights the machine was used was 95.5 % ( range , 45 to 100 % ) on constant CPAP , and 96.5 % ( range , 40 to 100 % ) on auto-CPAP ; the median apnea index recorded by the device was 0.40/h ( range , 0 to 2.40/h ) on constant CPAP , and 0.45/h ( range , 0 to 5.80/h ) on auto-CPAP ( differences not significant ) . The mean Epworth sleepiness score was significantly ( p < 0.01 ) lower on auto-CPAP ( 5.1 ; SD , 2.8 ) than on constant CPAP ( 6.1 ; SD , 2.8 ) . CONCLUSIONS In patients selected for a high within-night variability in pressure requirement , auto-CPAP administered via a GK418A device was equivalent to constant CPAP based on a titration night in the sleep laboratory . Subjective ratings for sleepiness were slightly lower on auto-CPAP STUDY OBJECTIVES The purpose of this study was to compare comfort parameters and pressure profiles of the AutoSet ( Resmed ) and the SOMNOsmart ( Weinmann ) , two auto-adjustable positive airway pressure ( APAP ) devices . SETTING The sleep disorders center of a university hospital . DESIGN A single-blind r and omized trial protocol was applied . A split night procedure allowed each patient to be treated in a crossover fashion with both APAP devices during one overnight study . PATIENTS AND METHODS Fifty consecutive obstructive sleep apnea ( OSA ) patients were recruited . Each patient filled out an evaluation form for both devices after the study night . Visual analogue scales were used to score four comfort measures . Three CPAP outcomes generated by the devices ( P50 , P95 and Pmax ) were assessed , compared with each other and correlated with the individually predicted CPAP ( Ppred ) . RESULTS Forty-five males and 5 females , mean age 53.0 years , body mass index 31.0 , were included . The mean apnea-hypopnea index was 58.7 , the mean arousal index was 54.3 . Mean CPAP-compliance before the titration study was 4.9 h per night . Comparison of the two devices regarding the effect on the subjective sleep quality parameters showed no differences . The AutoSet pressure outcomes correlated significantly better with Ppred in comparison with the SOMNOsmart . The P50 and P95 but not the Pmax values were significantly lower in the SOMNOsmart as compared with the AutoSet ( P50 : 5.1+/-1.3 vs 7.1 + /- 1.9 mbar , P<0.0001 ; P95 : 7.8+/-3.0 vs 9.6+/-1.9 mbar , P<0.0005 ; Pmax : 10.0+/-3.4 vs 10.8+/-1.8 mbar , NS ) . CONCLUSION While the subjective tolerance of the two APAP machines was comparable , these devices were characterized by different pressure profiles . The pressure parameters of the AutoSet correlated better with Ppred than those of the SOMNOsmart Conventional manually adjusted continuous positive airway pressure ( CPAP ) is an effective therapy for sleep-disordered breathing . We prospect ively investigated the efficacy of a self-titrating nasal CPAP system in the acute treatment of obstructive sleep apnea ( OSA ) syndrome . Twenty patients with moderately severe OSA [ apnea hypopnea index ( AHI ) > 15/hour ] were enrolled in a r and omized , controlled , prospect i ve clinical trial . An initial diagnostic sleep study was performed , followed by r and omization to a manually adjusted CPAP titration on one night and self titrating CPAP on the other night . On the conventional CPAP night , the CPAP was manually adjusted until abolition of all apneas and electroencephalographic ( EEG ) arousals , whereas the self-titrating CPAP was set in automatic mode at lights out . The self-titrating CPAP system utilized an algorithm based on airway vibration patterns to detect airway stability . The AHI decreased from 50.8 + /- 28.8/hour [ mean + /- st and ard deviation ( SD ) ] at baseline to 3.8 + /- 3.1/hour ( p < 0.005 ) during manually adjusted and 6.1 + /- 5.3/hour ( p < 0.005 ) during self-titrating CPAP . The arousal index ( Ar-I ) decreased from 34.1 + /- 23.1/hour ( baseline ) to 11.2 + /- 5.0/hour on manual adjustment ( p < 0.005 ) and 11.3 + /- 0.3/hour on self titration ( p < 0.005 ) , whereas total sleep time was unchanged . No significant differences in any measure of oxygenation or sleep architecture were observed between the manually adjusted and self-titrating CPAP nights except that the lowest arterial oxygen saturation ( SaO2 ) was higher with manual titration ( 84.4 + /- 4.2 % vs. 79.9 + /- 9.7 % , p < 0.05 ) . The maximum pressure required for abolition of apneas and arousals was significantly lower ( p < 0.05 ) during the self-titrating study ( 10.1 + /- 3.8 cmH2O ) as compared to manually adjusted CPAP ( 12.3 + /- 3.9 cmH2O ) . Failure to increase pressure and failure to maintain minimum pressure occurred in 7 of the 20 subjects during the self-titrating study . This required manual re setting of the system in five subjects , but the system self-corrected in two subjects . An unsupervised study would have result ed in undertreatment of OSA . Based on a single-night laboratory study , self-titrating CPAP was well tolerated and improved OSA and sleep architecture comparable to manually adjusted CPAP . The future modifications of this prototype will require further research to assess its efficacy and safety in the laboratory and home environments before its recommendation for general long-term use BACKGROUND Auto-CPAP machines used in the treatment of obstructive sleep apnoea ( OSA ) are design ed to vary the treatment pressure automatically in order always to apply the actually needed pressure . Consequently they should be able to achieve at least identical therapeutic effects as conventional constant pressure CPAP with a lower mean treatment pressure . The present study was design ed to evaluate the therapeutic efficacy and the treatment pressure of an auto-CPAP machine ( REM+auto ® , SEFAM ) in comparison with a conventional CPAP device . METHODS Following CPAP titration , 16 patients with OSA were allocated to receive conventional CPAP and auto-CPAP treatment under polysomnographic control in a r and omised order . After each treatment the patients were asked to assess the therapy using a question naire ; a vigilance test was also carried out and subjective daytime sleepiness was evaluated using the Epworth Sleepiness Scale ( ESS ) . RESULTS The mean ( SD ) apnoea/hypopnoea index ( AHI ) during auto-CPAP treatment was comparable with that during conventional CPAP treatment ( 4.2 ( 5.1 ) versus 3.6 ( 4.0 ) ) . Neither an analysis of sleep architecture nor the arousal index ( 7.4 ( 4.1 ) versus 7.0 ( 4.3 ) ) revealed any significant differences . Daytime sleepiness measured with the ESS was also comparable ( 5.3 ( 3.4 ) versus 6.5 ( 4.2 ) ) . The vigilance test showed normal values after both treatments in all patients with no significant differences . The mean pressure during auto-CPAP treatment ( 8.1 ( 2.9 ) mbar ) , however , was significantly higher than that employed in conventional CPAP treatment ( 7.6 ( 2.7 ) mbar ; mean difference 0.5 mbar ; 95 % CI 0.1 to 0.9 mbar ; p<0.05 ) . CONCLUSIONS Auto-CPAP was equally as effective as conventional CPAP with respect to therapeutic efficacy . The aim of reducing the treatment pressure with auto-CPAP , however , was not achieved The auto-CPAP ( Morphée Plus ) is characterized by its ability to modify the positive-pressure level applied during the night for the presence or absence of sleep-induced respiratory disorders . The aim of the study was to compare the efficacy of this new mode of CPAP therapy with that of conventional constant-CPAP in the treatment of sleep apnea/hypopnea syndrome ( SAHS ) . Sixteen patients with SAHS were r and omly allocated to two groups that were paired for age , apnea/hypopnea index , and mean sleep latency . In the auto-CPAP group , the pressure level could change within fixed limits in both directions ( + 2 to -4 cm H2O ) of the previously determined effective pressure level ( Peff ) . In the constant-CPAP group , patients used the same apparatus ( Morphée Plus ) in a constant mode at Peff level . At the beginning of the study , the Peff level was determined during a polysomnographic recording . Day-time vigilance was measured subjectively by a st and ardized question naire and objective ly by the maintenance of wakefulness test ( MWT ) ; Trailmaking tests ( TMT ) were used to evaluate cognitive functions . After 3 wk of home CPAP therapy , a control sleep study was done with the CPAP machine used in the protocol , and daytime vigilance and cognitive function tests were obtained . Baseline sleep and nocturnal breathing disorders characteristics did not differ between the two groups , and daytime vigilance and cognitive function abnormalities were similarily altered . In both groups , the apnea/hypopnea index was within normal range at the final CPAP sleep study . In the auto-CPAP group , 49.3 + /- 14.9 % ( mean + /- SD ) of home treatment time was spent at a pressure < or = Peff . Home amount of use estimated by the number of sleeping hours with a positive pressure applied was 6.5 + /- 1.0 h in the auto-CPAP group and 5.1 + /- 1.1 h in the constant-CPAP group ( p = 0.02 ) . During the control CPAP sleep study , the positive pressure level was significantly lower during Stage III-IV than during the other sleep stages ( p = 0.004 ) . The improvement in the MWT and the TMT observed with CPAP therapy was identical in both groups . We conclude that ( 1 ) the amount of use during CPAP treatment is higher with auto-CPAP than with constant-CPAP , and ( 2 ) Morphée+auto-CPAP is an efficient as conventional CPAP in correcting nocturnal breathing disorders , daytime sleepiness , and cognitive impairment in SAHS In a prospect i ve study aim ed at evaluating objective ly the compliance with nasal continuous positive airway pressure ( CPAP ) treatment , 233 obstructive sleep apnea ( OSA ) ( apnea index , > 10 apneas/hour ) patients and 36 nonapneic snorers were studied . The compliance to treatment was measured by the mean rate of use of the CPAP device , obtained from a built-in time counter . The follow-up period was 874 + /- 48 in OSA patients and 675 + /- 83 in snorers . CPAP was proposed to all OSA patients but only to those snorers who felt improved after an initial laboratory night on CPAP . Nineteen OSA patients refused CPAP . Of the 214 OSA patients who accepted CPAP , 181 are still on treatment , with a mean daily rate of use of 5.6 + /- 0.1 hours ( mean + /- SEM ) ; 22 patients stopped CPAP after a variable period of time ; 10 patients died and one acromegalic patient was considered cured after hypophysectomy for a pituitary adenoma . Depending upon the definition of acceptable compliance , the compliance rate in this group was between 77 % and 89 % . The mean rate of use was correlated with indices of disease severity ( apnea index , apnea+hypopnea index , minimal SaO2 during sleep , daytime PaO2 , pulmonary artery pressure ) . Thirty-six nonapneic snorers accepted CPAP . In this group , 26 are still on CPAP , with a mean daily rate of use of 5.4 + /- 0.5 hours ; one patient died ; one underwent uvolopalatopharyngoplasty without follow-up ; and eight stopped CPAP . The compliance rate in this group was between 58 % and 78 % . This study shows that CPAP is reasonably accepted by OSA patients as well as by nonapneic snorers . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To compare efficacy , compliance rates , and side effects of a new strapless oral interface , the Oracle , with available nasal masks over 8 weeks of use for the treatment of obstructive sleep apnea hypopnea syndrome ( OSAHS ) . METHODS A total of 38 patients with OSAHS ( respiratory disturbance index ( RDI ) > /=15/h ) were enrolled after the diagnostic polysomnogram for subsequent continuous positive airway pressure ( CPAP ) therapy . After r and omization , therapeutic pressures during a titration study were determined for 21 patients in the oral group and 17 patients in the nasal group . Comparisons for nasal and oral interfaces were made for baseline patient characteristics , average hours of CPAP use , side effects from therapy , and among question naires evaluating patients ' subjective responses to therapy at months 1 and 2 . RESULTS No significant difference was observed in the average hours of CPAP use between the oral ( 4.5+/-2.1 ; 5.5+/-2.6 ) and nasal groups ( 4.0+/-2.6 ; 4.8+/-2.5 ) for either month 1 or 2 ( P>0.05 ) . The dropout rates were similar for both groups after 8 weeks of therapy . However , patients in the nasal group had higher occurrences of side effects such as nasal congestion , dryness , and air leaks , whereas patients in the oral group experienced more oral dryness and gum pain . CONCLUSION Oral delivery of CPAP with the Oracle is an effective and suitable alternative for patients with OSAHS Proportional positive airway pressure ( PPAP ) was design ed to optimize airway pressure for the therapy of obstructive sleep apnoea ( OSA ) . In a r and omized crossover prospect i ve study , the clinical feasibility of PPAP and its immediate effects on the breathing disorder and sleep in comparison with continuous positive airway pressure ( CPAP ) was evaluated . Twelve patients requiring CPAP therapy underwent CPAP and PPAP titration in a r and om order . Obstructive and mixed respiratory events could be completely abolished with both forms of treatment . This efficacy could be achieved at a significantly lower mean mask pressure during PPAP titration ( 8.45+/-2.42 cmH2O ) compared to CPAP ( 9.96+/-2.7 cmH2O ) ( p=0.002 ) . The mean minimal arterial oxygen saturation ( Sa , O2 ) ( 82.8+/-6.5 % ) on the diagnostic night increased significantly ( p<0.001 ) to an average Sa , O2 of 93.35+/-1.71 % and 93.19+/-2.9 % during CPAP and PPAP titration . Total sleep time , slow wave sleep and rapid eye movement ( REM ) sleep increased significantly by the same amount during both CPAP and PPAP titration ( p<0.001 ) , while sleep stage nonrapid eye movement ( NREM ) 1 and 2 decreased . Six patients preferred the PPAP titration night , four patients did not have a preference , and two patients preferred CPAP . The present data show that proportional positive airway pressure is as effective as continuous positive airway pressure in eliminating obstructive events and has the same immediate effect on sleep . The lower average mask pressure during proportional positive airway pressure implies potential advantages compared to continuous positive airway pressure . Proportional positive airway pressure presents a new effective therapeutic approach to obstructive sleep apnoea OBJECTIVES To estimate the impact of small reductions in the population distribution of diastolic blood pressure ( DBP ) , such as those potentially achievable by population -wide lifestyle modification , on incidence of coronary heart disease ( CHD ) and stroke . DESIGN Published data from the Framingham Heart Study , a longitudinal cohort study , and from the National Health and Nutrition Examination Survey II , a national population survey , were used to examine the impact of a population -wide strategy aim ed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects . SETTING / PARTICIPANTS White men and women aged 35 to 64 years in the United States . MAIN OUTCOME MEASURES Incidence of CHD and stroke , including transient ischemic attacks ( TIAs ) . RESULTS Data from overviews of observational studies and r and omized trials suggest that a 2-mm Hg reduction in DBP would result in a 17 % decrease in the prevalence of hypertension as well as a 6 % reduction in the risk of CHD and a 15 % reduction in risk of stroke and TIAs . From an application of these results to US white men and women aged 35 to 64 years , it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher . It could prevent 84 % of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher . For stroke ( including TIAs ) , a population -wide 2-mm Hg reduction could prevent 93 % of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69 % of events for treatment for those with a DBP of 90 mm Hg or higher . A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone . Adding a population -based intervention to existing levels of hypertension treatment could prevent an estimated additional 67,000 CHD events ( 6 % ) and 34,000 stroke and TIA events ( 13 % ) annually among all those aged 35 to 64 years in the United States . CONCLUSIONS A small reduction of 2 mm Hg in DBP in the mean of the population distribution , in addition to medical treatment , could have a great public health impact on the number of CHD and stroke events prevented . Whether such DBP reductions can be achieved in the population through lifestyle interventions , in particular through sodium reduction , depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry , government agencies , and health education professionals St and ard practice for continuous positive airway pressure ( CPAP ) treatment in sleep apnea and hypopnea syndrome ( SAHS ) requires pressure titration during attended laboratory polysomnography . However , polysomnographic titration is expensive and time-consuming . The aim of this study was to ascertain , in a large sample of CPAP-naive patients , whether CPAP titration performed by an unattended domiciliary autoadjusted CPAP device or with a predicted formula was as effective as CPAP titration performed by full polysomnography . The main outcomes were the apnea-hypopnea index and the subjective daytime sleepiness . We included 360 patients with SAHS requiring CPAP treatment . Patients were r and omly allocated into three groups : st and ard , autoadjusted , and predicted formula titration with domiciliary adjustment . The follow-up period was 12 weeks . With CPAP treatment , the improvement in subjective sleepiness and apnea-hypopnea index was very similar in the three groups . There were no differences in the objective compliance of CPAP treatment and in the dropout rate of the three groups at the end of the follow-up . Autoadjusted titration at home and predicted formula titration with domiciliary adjustment can replace st and ard titration . These procedures could lead to considerable savings in cost and to significant reductions in the waiting list INTRODUCTION This French , multicenter , r and omized double-blind controlled trial tested the hypothesis that pressure reduction during exhalation ( C-Flex ; Respironics ; Murrysville , PA ) would improve continuous positive airway pressure ( CPAP ) compliance , comfort , and quality of life . METHODS Two hundred eighteen newly diagnosed sleep apnea patients ( seven centers ; mean [ + /- SD ] age , 55 + /- 11 years ; mean body mass index , 31 + /- 6 kg/m(2 ) ; mean apnea-hypopnea index , 44 + /- 21 events/h ) were r and omly assigned to receive 3 months of treatment with CPAP ( 108 patients ) or C-Flex ( 110 patients ) . Objective compliance , generic quality -of-life question naire ( SF-36 ) scores , disease-specific quality -of-life question naire ( Grenoble Sleep Apnea Quality of Life [ GrenobleSAQOL ] ) scores , and visual analog scales for CPAP comfort and side effects were determined at baseline and after 3 months . After 3 months , patients in the CPAP arm were moved to the C-Flex arm for 3 additional months ( open study ) . RESULTS An intention-to-treat analysis demonstrated that there were no differences at 3 months between C-Flex and CPAP use in terms of compliance , the rate of side effects , and comfort . Low compliers receiving CPAP therapy ( < 4 h of use ) significantly improved this outcome during the open study ( p = 0.04 ) . There was a significant improvement in six of eight of the SF-36 domain scores and in all of the domains of the GrenobleSAQOL scores in both groups using either CPAP or C-Flex . CONCLUSION In unselected sleep apnea patients , C-Flex was associated with similar outcomes to st and ard CPAP . Low compliers receiving CPAP therapy improved their adherence when moving to C-Flex . TRIAL REGISTRATION IS RCT N Register Identifier : 08065291 BACKGROUND Automatic CPAP has been developed to improve CPAP efficiency and compliance . Continually matching the effective pressure may be associated to more frequent arousals that could disturb sleep . The aim of the present study was to compare sleep architecture after one month 's home therapy with CPAP or with an AutoCPAP device . METHODS Twenty OSAS patients ( 18 M / 2 F ) after polysomnographic study with CPAP titration received either an automatic ( AutoSet T , ResMed , Sydney , Australia ) or a fixed level CPAP machine in a r and om , single blind fashion for one month . At the end of the home treatment period polysomnography was repeated while CPAP was administered by the same machine used at home . RESULTS There was no significant difference between groups in terms of age ( 50.0 vs 45.5 , NS ) , sex , BMI ( 38.3 vs 35.1 , NS ) , RDI ( 45.4 vs 48.0 , NS ) , and CPAP effective level ( 9.8 vs 10.8 , NS ) . After one month of therapy the correction of sleep respiratory disturbances and of sleep structure was satisfactory in both groups . No difference in any polysomnographic variable or in subjective sleepiness was found at re-evaluation . CONCLUSIONS The results of this study demonstrate that on average CPAP administered by a fixed CPAP machine and by the AutoSet T autoCPAP device has similar effects in improving respiratory function during sleep , nocturnal sleep architecture , and subjective daytime sleepiness after a one-month therapy . As autoCPAP devices are more expensive than fixed CPAP machines , their prescription should be considered only after a clear demonstration of an increase in compliance to treatment by these devices BACKGROUND A strong association between obstructive sleep apnea ( OSA ) and the risk for cardiovascular and cerebrovascular diseases has been reported . Continuous positive airway pressure ( CPAP ) is the first-line therapy for OSA , able not only to reduce daytime sleepiness but also to improve cardiovascular and metabolic outcomes . Autoadjusting CPAP ( APAP ) , an alternative treatment to CPAP , can reduce OSA symptoms while increasing long-term CPAP compliance without the high costs of CPAP titration . However , no data are available on the effects of APAP on cardiovascular risk factors METHODS We performed st and ard full polysomnography ; obtained plasma levels of glucose , insulin , and C-reactive protein ( CRP ) ; and measured systolic BP ( SBP ) and diastolic BP ( DBP ) in 31 patients with newly diagnosed , severe OSA . After st and ard CPAP titration , all subjects were r and omized to CPAP or APAP treatment . Measurements were obtained at baseline and after 3 months of treatment . RESULTS The two groups were similar in terms of age , sex , body mass index ( BMI ) , and severity of OSA . SBP , DBP , heart rate ( HR ) , homeostasis model assessment index ( HOMA-IR ) , and CRP were similar in the two groups . After 3 months of treatment , BMI , HR , and compliance to therapy were also comparable . OSA indexes were significantly reduced in both groups . Significant reductions in SBP , DBP , and HOMA-IR were observed in the CPAP group but not in the APAP group , while CRP plasma levels were similarly reduced . CONCLUSIONS Our results suggest that CPAP and APAP , despite significant effects on OSA indexes and symptoms , do not improve cardiovascular risk factors in the same fashion BACKGROUND Continuous positive airway pressure ( CPAP ) remains the treatment of choice for obstructive sleep apnea hypopnea ( OSAH ) . Auto-titrating CPAP ( APAP ) devices automatically adjust pressure and may improve treatment compliance compared to fixed CPAP ( F-CPAP ) . METHODS R and omized , prospect i ve , single-blind , crossover trial to compare efficacy , side effects , compliance , patient satisfaction and preference between APAP and F-CPAP therapy in patients with moderate to severe OSAH . There were two treatment periods of 4 weeks each ( APAP and F-CPAP ) , separated by a 2-week washout period . RESULTS Ten CPAP-naive OSAH patients ( 9 males ) completed the study . They had Mean + /- SD age of 44.9 + /- 9.7 years ; body mass index of 35.9 + /- 12.9 kg/m2 and apnea/hypopnea index ( AHI ) of 47.2 + /- 35.6 . Both forms of therapy were equally effective in improving the symptoms and in reducing the AHI . Both forms of therapy were associated with frequent side effects and had similar patient compliance . At the end of the study , more patients ( 6 - 1 ) preferred F-CPAP to A-CPAP therapy . CONCLUSION A-PAP was as effective as F-CPAP in the treatment of OSAH but was not associated with fewer side effects , better compliance , better satisfaction or increased patient preference Effectiveness of continuous positive airway pressure ( CPAP ) as a treatment of obstructive sleep apnea can be limited by poor compliance , but little is known about how to improve compliance . We performed a r and omized , controlled clinical trial among 33 subjects of two interventions to improve compliance . One group of subjects received weekly phone calls to uncover any problems and encourage use , another received written information about sleep apnea and the importance of regular CPAP use , and a third served as control subjects . We found that intervention improved CPAP compliance ( p = 0.059 ) and that the effect was particularly strong when intervention occurred during the first month of CPAP treatment ( p = 0.004 ) . Although the sample size did not allow definitive investigation of other explanatory variables , subjects with lower levels of education or those with relatives who used CPAP may have benefited from intervention more than other subjects . We conclude that simple , inexpensive efforts to improve compliance with CPAP can be effective , especially when applied at the start of CPAP treatment , but optimal intervention may vary with certain patient characteristics Continuous positive airway pressure ( CPAP ) therapy is widely prescribed for patients with the sleep apnea/hypopnea syndrome ( SAHS ) , but the use of CPAP for such patients is disappointingly low . We postulated that providing intensive educational programs and nursing support to SAHS patients might improve CPAP use and outcomes . We also examined the hypothesis that CPAP use would be greater among patients who had initiated their own referral than among those asked to seek help by a partner . We r and omized 80 consecutive , new patients with SAHS to receive either usual support or additional nursing input including CPAP education at home and involving their partners , a 3-night trial of CPAP in our institution 's sleep center , and additional home visits once they had begun CPAP . The primary outcome variable was objective CPAP use ; symptoms , mood , and cognitive function were also assessed after 6 mo . CPAP use over 6 mo was greater ( p = 0.003 ) among patients receiving intensive than among those receiving st and ard support ( 5.4 + /- 0.3 versus 3.9 + /- 0 . 4 h/night [ mean + /- SEM ] ) , with greater improvements ( p < 0.05 ) in SAHS symptoms , mood , and reaction time in the intensively supported group . CPAP use was greater ( p = 0.002 ) among patients who initiated their own referrals . CPAP use and outcomes of therapy can be improved by provision of a nurse-led intensive CPAP education and support program . CPAP use is lower among patients whose partners ask them to seek treatment Purpose Continuous positive airway pressure ( CPAP ) is the therapy of choice for the treatment of obstructive sleep apnea ( OSA ) . Not all patients can use CPAP therapy with adequate compliance . There is a need to develop more comfortable modes . Auto bi-level Pressure Relief-Positive Airway Pressure ( ABPR-PAP ) can be an alternative . We conducted a prospect i ve double-blind , r and omised trial to evaluate the efficacy and compliance of ABPR-PAP compared with CPAP in OSA patients . Methods We included 35 CPAP naive patients ( age 53.3 ± 10.3 years , BMI 31.0 ± 5.0 kg/m2 , ESS 10.0 ± 4.2 ) diagnosed with moderate to severe OSA who underwent a successful CPAP titration . Patients were r and omised into the CPAP or the ABPR-PAP treatment group . We used the same device ( BIPAP ® Auto , Philips Respironics ) for CPAP or ABPR-PAP . Apnea – hypopnea index ( AHI ) was determined using polysomnography before ( AHI 40.6 ± 18.3 per hour ) and after treatment . Results Eighteen patients received CPAP and the remaining 17 received APBR-PAP . Groups were similar in terms of demographics and OSA severity . There were no serious adverse events during the trial . CPAP was fixed by a sleep expert and ABPR-PAP varied ( range 5–15 cmH2O ) . AHI decreased in the CPAP group to 6.4 ± 5.7 per hour and in the ABPR-PAP group to 4.8 ± 3.6 per hour in the first night ( N = 35 ) . After 3 months , the AHI decreased in the CPAP group to 4.4 ± 5.3 per hour and in the ABPR-PAP group to 2.6 ± 3.8 per hour ( N = 32 ) . Differences between the groups were not statistically significant . There were no differences in compliance . Conclusions ABPR-PAP is a promising new ventilation mode that enables effective treatment of OSA patients Purpose To determine the effect of a controlled heated breathing tube humidifier ( cHH ) on the quality of life ( QOL ) , compliance and nasopharyngeal side effects during continuous positive airway pressure ( CPAP ) therapy in patients with obstructive sleep apnea syndrome ( OSAS ) in comparison with conventional CPAP . Methods In this prospect i ve r and omised cross-over study , 44 patients with OSAS were investigated . During the first two consecutive treatment nights monitored by polysomnography , patients were r and omly assigned to receive CPAP with or without cHH . Patients were then r and omised to receive one of the treatment modalities at home for 4 weeks . Compliance was recorded and question naires assessing side effects and QOL were administered . Results Sleep parameters measured during the nights in the sleep laboratory did not change . The same result applied to QOL and compliance measured after 4 weeks . During the first two nights we found significant differences between CPAP with and without cHH for dryness of mouth ( 2.0 ± 1.4 vs. 1.4 ± 1.6 ) in favour of cHH ( p < 0.05 ) . Evaluation of coldness of the face showed improvement whereas waking up due to wetness on the face ( 0.3 ± 0.6 vs. 0.6 ± 0.8 ; p < 0.05 ) was slightly increased . Data after 4 weeks confirmed these findings with further subjective improvement in the reduction of side effects . Conclusions By the using of the technology of cHH QOL and compliance did not improve . The side effects of CPAP therapy without humidification with respect to nasopharyngeal dryness , however , was reduced immediately as well as during the first weeks of treatment Effective compliance ( time spent at the effective pressure ) with nasal CPAP in obstructive sleep apnea has been reported to be poor . The aim of our study was to evaluate effective compliance in a large European multicenter study . One hundred twenty-one consecutive newly treated patients ( initial apnea-hypopnea index [ AHI ] = 62.0 + /- 29 . 5/h , AHI under CPAP = 6.4 + /- 8.1/h , CPAP pressure = 8.7 + /- 2.6 cm H(2)O , BMI = 33.1 + /- 6.8 kg/m(2 ) ) were r and omly allocated to a group with ( MC(+ ) ) ( n = 58 ) or without ( MC(- ) ) ( n = 63 ) a control unit measuring effective compliance at 1 , 2 , and 3 mo , which was compared with the built-in time counter data . MC(+ ) data were 94 + /- 10 , 98 + /- 5 , and 96 + /- 9 % of counter data at 1 , 2 , and 3 mo , respectively . Using criteria of regular use already reported in the literature ( at least 4 h of nCPAP per day of use and nCPAP administered more than 70 % of the days ) we found 77 , 82 , and 79 % compliant patients at 1 , 2 , and 3 mo , respectively , 79 % of the patients meeting these criteria each month . Although there were no pulmonary functions or polysomnographic differences between the two subgroups , the compliant patients did report a greater improvement in minor symptoms . We found a close correlation between effective use of CPAP and the machine run time . The main result of our study was a higher effective compliance than previously reported , approximately 80 % of the patients being regular users versus 46 % in a previously published study . This may result from different technical and medical follow-up STUDY OBJECTIVES Despite widespread agreement that continuous positive airway pressure is effective therapy for obstructive sleep apnea , it is estimated that 50 % of patients recommended for therapy are noncompliant 1 year later . Interventions to improve compliance in such patients have not been studied . We evaluated a 2 phase intervention program to improve compliance in sleep apnea patients previously noncompliant with continuous positive airway pressure . METHODS 204 patients with previously diagnosed obstructive sleep apnea and noncompliant with continuous positive airway pressure were enrolled . Phase 1 evaluated st and ard interventions to improve therapy compliance , including mask optimization , heated humidification , topical nasal therapy , and sleep apnea education . Persistently noncompliant patients proceeded to phase 2 , where compliance was compared in double-blind r and omized fashion between st and ard continuous positive airway pressure and flexible bilevel positive airway pressure . RESULTS 49 ( 24 % ) of 204 previously noncompliant patients became compliant ( average nightly use > or = 4 hours ) after st and ard interventions . Then 104 of the 155 persistently noncompliant patients agreed to continue and were r and omized to either CPAP or flexible bilevel positive airway pressure retitration and treatment for an additional ninety days . At follow-up 15 ( 28 % ) of the 53 r and omized to CPAP and 25 ( 49 % ) of the 51 r and omized to flexible bilevel positive airway pressure ( p = 0.03 ) achieved compliance . CONCLUSIONS A two phase intervention program , first employing st and ard interventions , followed by a change to flexible bilevel airway pressure , can achieve improved compliance in patients previously noncompliant with continuous positive airway pressure BACKGROUND AND PURPOSE Compliance with continuous positive airway pressure ( CPAP ) treatment in obstructive sleep apnoea syndrome ( OSAS ) may be difficult . Patient education is important but strategies and their outcomes are not clear . PATIENTS AND METHODS We studied the effects of four education strategies on compliance and quality of life changes with CPAP treatment in seven centres in the French ANTADIR homecare network . Patients received from prescribers either a simple oral explanation ( SP ) or an oral and written explanation ( RP ) of CPAP use . In addition , they received from homecare technicians either a single home visit ( SH ) at CPAP onset or repeated home visits at CPAP onset and at 1 week , 1 month and 3 months after ( RH ) . Compliance and quality of life were evaluated at CPAP onset , and at 3 , 6 and 12 months after initiation of treatment . RESULTS One hundred twelve patients with severe OSAS ( mean age 58+/-11 year , apnoea-hypopnoea index 58+/-25/h ) were allocated r and omly to groups ( SP+SH ; SP+RH ; RP+SH ; RP+RH ) with no initial differences . Quality of life , evaluated by the generic SF-36 question naire , improved in the combined emotional domains . Compliance was over 5h in all four education groups . These effects were sustained over 12 months and were not different between the four groups . We conclude that st and ard education strategies for CPAP induction in France are sufficient for good compliance and improved quality of life with CPAP . Education with reinforced input should be focussed on identified subgroups prone to problems STUDY OBJECTIVE To determine whether the addition of heated humidification at treatment initiation with nasal continuous positive airway pressure ( CPAP ) would lead to better CPAP compliance and improve quality of life and subjective sleepiness in patients with sleep apnea . DESIGN R and omized controlled trial . SETTING An academic sleep center located at a Veterans Affairs hospital . PATIENTS Ninety-eight patients with obstructive sleep apnea who had not received nasal CPAP previously . MEASUREMENTS AND RESULTS Patients received heated humidification at CPAP initiation in the treatment group . In the control group , patients could receive heated humidification only if they had upper airway symptoms that could not be treated successfully with simpler measures . Patients were followed up at 1 month , 3 months , and 12 months . Outcome measures were compliance with nasal CPAP ( mean hours per night at effective pressure ) , quality of life as measured by the Calgary sleep apnea quality of life index , subjective sleepiness measured with the Epworth sleepiness scale , and CPAP side effects . There was no difference in CPAP compliance between groups . Quality of life and subjective sleepiness improved in both groups with nasal CPAP therapy , but there was no difference in the extent of improvement between groups . The overall CPAP side effect score was similar in both groups , but individual symptoms of dry nose and dry mouth and throat were significantly lower in the heated humidification group . CONCLUSIONS The addition of heated humidification when nasal CPAP was instituted did not lead to better compliance , greater improvement in sleepiness , or improved quality of life , but was associated with fewer symptoms attributable to the upper airway We tested the hypothesis that continuous positive airway pressure ( CPAP ) use and outcomes can be improved by an autotitrating CPAP device in patients with obstructive sleep apnea-hypopnea syndrome ( OSAHS ) who require higher CPAP ( 10 cm H2O or more ) . In this multisite r and omized single-blind cross-over study , 44 patients ( mean age , 49 + /- 10 years ) were r and omized to 6 weeks at laboratory-determined fixed pressure and 6 weeks on autotitrating CPAP . Average nightly use was greater in automatic mode ( 306 versus 271 minutes , p = 0.005 ) ; median and 95th centile pressures in automatic mode were lower ( p < 0.002 ) . Automatic CPAP result ed in better SF-36 Vitality scores ( 65 + /- 20 versus 58 + /- 23 , p < 0.05 ) and mental health scores ( 80 + /- 14 versus 75 + /- 18 , p < 0.05 ) , but no significant difference in Epworth score ( p = 0.065 ) . During automatic therapy , patients reported more restful sleep , better quality sleep , less discomfort from pressure , and less trouble getting to sleep for both the first week of therapy and for the averaged scores for Weeks 2 - 6 ( all p values < 0.006 ) . Patients who require higher fixed CPAP use autotitrating CPAP more and report greater benefit from this therapy BACKGROUND : The addition of heated humidification to CPAP has been shown to improve nasal adverse effects in subjects with obstructive sleep apnea ( OSA ) . However , current data regarding improvement in CPAP adherence is conflicting . Furthermore , there are no data from a tropical climate area with a high humidity level . METHODS : In this prospect i ve r and omized crossover study conducted in Thail and , subjects with moderate to severe OSA with nasopharyngeal symptoms post-split-night study were enrolled in the study . Subjects were r and omly assigned to receive CPAP with or without heated humidification for 4 weeks and then crossed over . Information on CPAP adherence , quality of life assessed by the Functional Outcomes of Sleep Question naire , nasopharyngeal symptoms assessed by a modified XERO question naire , and bedroom ambient humidity and temperature data were obtained . RESULTS : Data were collected on 20 subjects with OSA during the period of January to December 2014 . Although the addition of heated humidification appeared to improve average hours of use for all days when compared with conventional CPAP , the difference was not statistically significant ( CPAP with heated humidification = 4.6 ± 1.7 h/night ; conventional CPAP = 4.0 ± 1.7 h/night , P = .1 ) . However , the addition of heated humidification improved CPAP adherence on the days of use ( 5.5 ± 1.5 h/night ) compared with conventional CPAP ( 5.2 ± 1.4 h/night ) , P = .033 . Quality of life was also improved according to the Functional Outcomes of Sleep Question naire score ( median 17.6 [ interquartile range 3.5 ] ) in the heated humidification group compared with conventional CPAP group ( median 17.6 [ interquartile range 4.5 ] ) , P = .046 . Significant reduction in the dry throat/sore throat symptom was noted only when CPAP with heated humidification was used . CONCLUSIONS : Even in a tropical climate area , CPAP adherence and quality of life appeared to improve when heated humidification was employed in subjects with moderate to severe OSA with nasopharyngeal symptoms post-split-night polysomnography . The improvement may be related to a reduction in the dry throat/sore throat symptom STUDY OBJECTIVES To obtain efficacy , objective compliance , and self- assessment data from obstructive sleep apnea syndrome ( OSAS ) patients treated with continuous positive airway pressure ( CPAP ) or a novel bilevel ( NBL ) therapy . DESIGN R and omized , controlled , double-blind trial . SETTING Home treatment after diagnosis and titration by split-night polysomnography ( PSG ) in a sleep laboratory . PATIENTS Twenty-seven adults ( 22 men ) newly referred for suspected OSAS but without concomitant medical or sleep disorders . INTERVENTIONS If the subject 's apnea-hypopnea index was greater than 10 and less than 100 , the CPAP was titrated during PSG and then followed by NBL titration . Treatment was r and omly and blindly set to either CPAP or NBL mode for 1 month . MEASUREMENTS & RESULTS There were no significant baseline group differences in age , body mass index , apnea-hypopnea index ( mean + /- SD , CPAP group vs NBL group of 46.1 + /- 23.1/hour vs 41.8 + /- 25.8 ) , CPAP requirement , or scores on the Epworth Sleepiness Scale and Functional Outcomes of Sleep Question naire . Treatment with CPAP and NBL equivalently reduced the apnea-hypopnea index during the laboratory titration ( 7.6 + /- 11.9/hour vs. 3.7 + /- 4.4 , respectively ) . At 1 month , there were no significant group compliance differences as determined by percentage of nights with at least 4 hours of use ( CPAP , 80.5 + /- 24 vs NBL , 77.6 + /- 24.8 ) and hours of use per night ( CPAP , 5.6 + /- 1.4 hours/night vs NBL , 5.6 + /- 1.7 ) . Similar improvements were seen in scores on the Epworth Sleepiness Scale and Functional Outcomes of Sleep Question naire . CONCLUSIONS The NBL appeared to be as effective as CPAP for the treatment of OSAS but offered no advantages in patients receiving first-time therapy for OSAS We evaluated the efficacy of two different continuous positive airway pressure devices with automatic mask pressure adjustment ( autoCPAP ) in comparison with fixed CPAP in treating obstructive sleep apnea syndrome in 29 patients . The mean ( + /- SE ) apnea-hypopnea index was 46 + /- 4 per hour and the Epworth score was 14.2 + /- 0.7 . Patients were treated over three consecutive 1-month periods with three regimens in r and om order : an autoCPAP device responding to apnea-hypopnea and snoring , another autoCPAP device responding to snoring and changes in flow contour , and fixed CPAP at the 90th pressure percentile titrated by autoCPAP over 2 weeks . Allowed pressure in the autoCPAP mode was 4 to 15 cm H2O . At the end of each treatment period , symptoms , quality of life , vigilance , and nocturnal breathing disturbances were evaluated . All three treatment modalities improved symptoms , quality -of-life domains , and apnea-hypopnea index significantly and to a similar degree . Mean ( + /- SE ) maintenance-of-wakefulness time increased by 4.5 + /- 1.8 , 6.0 + /- 1.5 , and 6.1 + /- 1.4 minutes with DeVilbiss AutoAdjust LT , AutoSet T , and fixed-pressure CPAP , respectively ( p<0.001 vs. baseline , p = not significant for comparisons among the three modalities ) . We conclude that both autoCPAP devices were equally effective as fixed-pressure CPAP in improving major outcomes during short-term therapy of sleep apnea STUDY OBJECTIVES To determine the therapeutic efficacy and viability of a novel oral interface for continuous positive airway pressure ( CPAP ) compared with conventional nasal interfaces . DESIGN A r and omized single-blind crossover study . SETTING Hospital-based sleep laboratory . PATIENTS OR PARTICIPANTS 21 CPAP-naïve patients with obstructive sleep apnea ( baseline apnea-hypopnea index , 85 + /- 36 ) INTERVENTIONS : Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS : Patients were each treated for two 4-week periods using nasal CPAP and oral CPAP . The CPAP titrations were undertaken at the start of each treatment arm . Outcome measures were recorded at baseline and at the end of each treatment arm . These included polysomnography variables , CPAP compliance , subjective sleepiness , obstructive sleep apnea symptom ratings , and adverse effects . There were no significant differences between oral and nasal interfaces for the on-CPAP frequency of apneas and hypopneas ( mean difference , nasal-oral [ 95%CI ] = -4.6[-10.1 - 1.0]/h ; P = 0.06 ) or arousals ( -3.0 [-7.8 - 1.8]/h ; P = 0.23 ) . There were also no statistically significant differences between interfaces for scores on the Epworth Sleepiness Scale ( -0.7 [ -3.1 - 1.7 ] ; P = 0.20 ) , obstructive sleep apnea symptoms ( -7.7 [ -17.7 - 2.4 ] ; P = 0.052 ) , CPAP compliance ( 0.3 [ -0.5 - 1.1 ] h/night ; P = 0.50 ) , CPAP pressure ( 0.05 [ -0.66 - 0.76 ] cmH20 ; P = 0.73 ) , CPAP side effects scores ( -2.0 [ -5.3 - 1.4 ] ; P = 0.23 ) , or mask preference ( P = 0.407 ) . In addition , both nasal and oral interfaces significantly improved polysomnographic variables , Epworth Sleepiness Scale scores , obstructive sleep apnea symptoms , and CPAP compliance from baseline ( all P < 0.05 ) . CONCLUSIONS This preliminary study indicates that oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating obstructive sleep apnea . Additional large studies are required to determine the range of clinical situations where oral CPAP is indicated Introduction Obstructive sleep apnea ( OSA ) is often treated with continuous positive airway pressure ( CPAP ) but the effectiveness of treatment is probably limited by poor compliance . CPAP manufacturers are thus attempting to devise more comfortable PAP devices in an effort to improve compliance . An example of such a novel device is Flexible expiratory-modulated PAP ( C-Flex mode Respironics REMstar Pro , Murraysville , PA , USA ) . Material s and methods We aim ed to compare compliance between C-Flex and st and ard CPAP in patients with severe OSA in a r and omised controlled trial . Nineteen patients with severe OSA ( mean ± SD Apnea Hypopnea Index = 78 ± 33/h , Epworth 14 ± 4 , PAP 8–17 cm H2O , BMI = 39 ± 10 kg/m2 ) and aged 20–63 years were r and omly assigned to 4 weeks of either C-Flex ( setting II , n = 9 ) or CPAP ( n = 10 ) . Results Patients treated with C-Flex exhibited a trend toward higher compliance with their PAP devices compared to patients treated with st and ard CPAP ( 4.7 ± 2.9 vs. 3.0 ± 2.1 h/night , p = 0.15 , effect size = 0.68 ) . Paradoxically , improvements in subjective sleepiness ( Epworth Sleepiness Scale ) were greater in those who received CPAP than C-Flex ( 8.1 + 4.9 vs. 2.1 + 4.0 points , p = 0.014 , effect size = 1.46 ) . Improvements in objective wakefulness ( Modified Maintenance of Wakefulness Test ) and simple reaction times ( Psychomotor Vigilance Task ) were not significantly different between treatments . This r and omised trial provides some evidence that C-Flex might increase initial treatment compliance , compared to CPAP , in patients with severe OSA . However , this trend toward greater compliance was not associated with better short-term treatment outcomes for patients . These findings need to be confirmed in a larger , longer-term trial STUDY OBJECTIVES There are no clinical data comparing adherence and quality of life between auto-adjusting positive airway pressure ( APAP ) and two different flex positive airway pressure ( PAP ) devices ( A-Flex , C-Flex ) in patients with obstructive sleep apnea ( OSA ) . DESIGN AND SETTING Ninety-three patients in whom OSA was newly diagnosed were r and omly assigned to receive 3 mo of APAP ( n = 31 ) , APAP with C-Flex ( n = 31 ) , or APAP with A-Flex ( n = 31 ) . Objective adherence was determined after 3 mo of CPAP treatment , and the Epworth Sleepiness Scale ( ESS ) , Pittsburgh Sleep Quality Index ( PSQI ) , and Calgary Sleep Apnea Quality of Life Index ( SAQLI ) were examined at baseline and after 3 mo . After 3 mo , patients in the APAP with A-Flex group and those in the APAP with C-Flex group were crossed over and those in the APAP group were switched to A-Flex for an additional 3 mo . MEASUREMENTS AND RESULTS The groups were similar demographically . Treatment adherence during the first 3 mo was significantly greater in the APAP with C-Flex group ( APAP with C-Flex : 5.19 ± 1.84 h/night versus APAP : 3.96 ± 1.66 h/night versus APAP with A-Flex : 4.27 ± 2.12 h/night , P = 0.04 ) . There was a significant improvement in two of four of the SAQLI domain scores and in the ESS and PSQI in the APAP with C-Flex group . Adherence significantly improved among the poor compliers ( < 4 h/night of use ) in the APAP group after change to APAP with A-Flex ( P = 0.01 ) . CONCLUSIONS Of these three modes of PAP delivery , adherence was greatest with APAP with C-Flex . CLINICAL TRIAL REGISTRATION URL : http://www . clinical trials.gov . Unique identifier : NCT00873977 Pressure intolerance is a reason for poor acceptance and subsequent compliance in some patients starting treatment with continuous positive airway pressure ( CPAP ) . In unselected population s initiating CPAP ; different types of pressure generating device have not been found to improve compliance . We hypothesized that using Bi-level PAP for patients who reported pressure related discomfort as a cause for poor compliance with CPAP might increase their hours of treatment use . Patients using CPAP < 4 h/night with symptoms to suggest pressure intolerance were r and omized to receive either a Bi-level PAP device or a new CPAP for 4 weeks . Following a washout period of 2 weeks , they were crossed over to the other device for 4 weeks . Twenty eight volunteers completed the protocol . Compared to the baseline ( mean 1.49 h per night ) , improvement in compliance was noticed when changed to a new CPAP ( 2.23 h , p = 0.006 ) or Bi-level PAP ( 2.73 h , p < 0.001 ) . The trend suggesting superior compliance with a Bi-level PAP device compared to new CPAP was not significant ( p = 0.059 ) and there were no differences in subjective or objective measures of sleepiness . The results of this study suggest that routine intervention with Bi-level PAP in this group of sub-optimally compliant individuals was not very effective in improving PAP usage . There is however a subgroup of patients who complains of difficulty with exhalation ; where favorable trends towards improved compliance were observed on Bi-level PAP RATIONALE The incidence of obesity hypoventilation syndrome ( OHS ) may be increasing in parallel with the present obesity epidemic . Despite extensive noninvasive ventilation ( NIV ) and continuous positive airway pressure ( CPAP ) use in patients with OHS , information regarding efficacy is limited . OBJECTIVES We performed a large , multicenter r and omized controlled study to determine the comparative efficacy of NIV , CPAP , and lifestyle modification ( control group ) using daytime PaCO2 as the main outcome measure . METHODS Sequentially screened patients with OHS with severe sleep apnea were r and omized into the above-mentioned groups for a 2-month follow up . Arterial blood gas parameters , clinical symptoms , health-related quality -of-life assessment s , polysomnography , spirometry , 6-minute-walk distance , dropouts , compliance , and side effects were evaluated . Statistical analysis was performed using intention-to-treat analysis , although adjustments for CPAP and NIV compliance were also analyzed . MEASUREMENTS AND MAIN RESULTS In total , 351 patients were selected , and 221 were r and omized . NIV yielded the greatest improvement in PaCO2 and bicarbonate , with significant differences relative to the control group but not relative to the CPAP group . In the CPAP group , PaCO2 improvement was significantly different than in the control group only after CPAP compliance adjustment . Additionally , clinical symptoms and polysomnographic parameters improved similarly with NIV and CPAP relative to the control . However , some health-related quality -of-life assessment s , the spirometry , and 6-minute-walk distance results improved more with NIV than with CPAP . Dropouts were similar between groups , and compliance and secondary effects were similar between NIV and CPAP . CONCLUSIONS NIV and CPAP were more effective than lifestyle modification in improving clinical symptoms and polysomnographic parameters , although NIV yielded better respiratory functional improvements than did CPAP . Long-term studies must demonstrate whether this functional improvement has relevant implication s. Clinical trial registered with www . clinical trials.gov ( NCT01405976 ) BACKGROUND CPAP remains the treatment of choice for Obstructive Sleep Apnea Hypopnea Syndrome ( OSAHS ) , but compliance with CPAP is poor . Of many interventions tried to improve CPAP compliance , only education and humidification have been shown to be of benefit . Our purpose was to develop and pilot test a video to enhance patient underst and ing of obstructive sleep apnea and of the purpose , logistics , and benefits of CPAP use in patients newly diagnosed with OSAHS . A patient 's CPAP compliance in the first few weeks after starting its use is predictive of long-term compliance with CPAP treatment . It is imperative that patients grasp at the outset both the severity of OSAHS and the effectiveness of CPAP therapy . METHODS An educational video script was written based on recommendations for patient educational video material s and covering identified misconceptions about OSAHS and perceived barriers to CPAP use . The videotape is 15 min in length and features two middle-aged males , one African-American and one Euro-American , discussing OSAHS and CPAP in a factory break room . RESULTS In a r and omized two-group design with a control group , patients with newly diagnosed OSAHS , and who viewed the CPAP educational video on their first clinic , were significantly more likely to use their machine and to return for a 1-month clinic visit than were those in the control group . CONCLUSION Viewing of a patient education video at the initial visit was found to significantly improve the rate of return for the follow-up visit Autoadjusting CPAP devices ( APAP ) are design ed to continuously adjust the positive pressure to the required levels , and thus increase treatment quality and patient compliance . The results of APAP treatment strongly depend on the control mechanism of the respective APAP device . In agreement with other working groups , we have recently shown that the forced oscillation technique ( FOT ) is capable of detecting incipient upper airway obstruction prior to physiological reactions such as the onset of increasing esophageal pressure swings or microarousals . Therefore we studied efficacy and acceptance of a novel APAP device controlled exclusively by FOT . 100 consecutive patients with OSAS confirmed by polysomnography ( mean AHI 47.9 + /- 22.6 ) and daytime sleepiness ( Epworth sleepiness scale , ESS 12.6 + /- 3.9 ) were r and omized to either APAP treatment ( n = 50 ) or conventional CPAP treatment ( n = 50 ) . Polysomnographies were performed at the second treatment night and subjective sleepiness ( modified ESS ) was established in the morning . The respiratory disturbance was largely normalized in both treatment groups in the second treatment night ( AHI 4.7 + /- 5.3 vs. 3.7 + /- 3.4 ; n.s . ) . Both groups showed largely improved sleep profiles and had markedly reduced ESS-scores ( 6.6 + /- 3.6 vs. 7.0 + /- 3.4 ; n.s . ) . The mean treatment pressure during APAP was significantly lower than during CPAP treatment ( 6.0 + /- 2.0 vs. 9.0 + /- 1.8 mbar ; p < 0.001 ) . There were no significant differences between APAP and CPAP treatment in any parameter of efficacy or acceptance . APAP treatment with this device controlled exclusively by FOT is well accepted by the patients and permits an adequate treatment of OSAS without the need for invidiual CPAP titration Current re sources are inadequate to meet the dem and for polysomnography , result ing in long waiting lists . This study aim ed to evaluate the role of arbitrary-pressure continuous positive airway pressure ( CPAP ) as a method to reduce delays in commencing treatment . The study was of an open , r and omized , parallel design . Ninety-one subjects with obstructive sleep apnea syndrome were r and omized to either arbitrary-pressure CPAP based on body mass index before treatment polysomnography or to CPAP at setting s determined by polysomnography . Both interventions result ed in similar improvements in clinical outcomes as determined by Epworth Sleepiness Score , Short Form-36 Quality of Life question naire , objective compliance , and subjective attitudes to treatment . There was higher sleep efficiency at treatment polysomnography in the group commenced at arbitrary pressure ( 81.8 + /- 10.1 % [ mean + /- SD ] compared with 72.2 + /- 18.0 % , p = 0.01 ) . Subjects unable to tolerate CPAP were identified by the use of arbitrary pressure , leading to a reduction in the proportion of " wasted " treatment polysomnograms ( studies performed in subjects not persisting with treatment ) relative to commencing therapy after treatment polysomnography ( 3 of 39 compared with 12 of 35 , p = 0.01 ) . This approach to initiating treatment with CPAP appears feasible when there are long waiting lists for polysomnography BACKGROUND AND PURPOSE Obstructive sleep apnea-hypopnea syndrome ( OSAHS ) patients undergo continuous positive airway pressure ( CPAP ) treatment for the first time on titration night , and then the effect of overnight CPAP treatment is estimated immediately . The purpose of this study is to compare the effects of CPAP-pretreated and non-pretreated on patients with OSAHS . METHODS Prospect i ve r and omized , controlled parallel study was performed . Seventy patients with OSAHS received autoadjusted CPAP treatment for 2 months and then received the st and ard manual titration ( CPAP-pretreated group ) . The other 70 did not receive any CPAP treatment before receiving the st and ard manual titration ( non-CPAP-pretreated group ) . RESULTS The CPAP-pretreated group had significantly improved sleep efficiency and arousal index in non-rapid eye movement ( NREM ) sleep compared with the initial CPAP group at titration , whereas there were no significant differences between the two groups in other sleep parameters . Eight patients in the non-CPAP-pretreated group discontinued CPAP treatment 9 months after the titration , whereas one patient in the CPAP-pretreated group discontinued treatment . CONCLUSIONS A preceding CPAP treatment showed minimal effects on sleep parameters on titration night and subsequent CPAP compliance rate , although it was speculated that this preceding treatment might be of benefit for better compliance in some patients STUDY OBJECTIVES To compare compliance and treatment response between continuous positive airway pressure ( CPAP ) and auto-titrating positive airway pressure ( APAP ) and to develop selection criteria for the use of APAP . DESIGN R and omized , single-blinded , parallel crossover study . SETTING Tertiary referral sleep disorders center . PATIENTS Consecutive patients with obstructive sleep apnea syndrome requiring treatment with CPAP . INTERVENTIONS 2-month treatment each of conventional CPAP and APAP in r and om order comparing objective compliance , Epworth Sleepiness Score , SF-36 Health Survey , visual-analog measures of ease of and attitude to treatment , side effects , and treatment pressures or system leaks obtained from the Autoset T device . MEASUREMENTS AND RESULTS There were no differences between treatment modes in overall compliance ( CPAP 4.86 + /- 2.65 , APAP 5.05 + /- 2.38 hours per night , P = .14 ) , Epworth Sleepiness Scale scores ( baseline 12.4 + /- 5.1 , CPAP 8.4 + /- 5.2 , APAP 7.9 + /- 4.8 , P < .001 relative to baseline , NS between modes ) , SF-36 scores ( significant improvements in Role Physical and Vitality domains relative to baseline , P < .001 but NS between modes ) . There were fewer reported side effects in APAP mode ( CPAP 28 , APAP 15 reports , P = .02 ) and compliance was greater with APAP in those reporting any side effect ( 95 % confidence interval CPAP 0 - 6.8 , APAP 2.9 - 7.8 hours per night , P < .001 ) . APAP delivered significantly lower median and 95th centile airway pressures and fewer system leaks . CONCLUSIONS Compliance , subjective sleepiness , and quality of life are similar between patients who used CPAP and APAP . APAP delivers lower pressures and results in lower-pressure leaks and fewer reported side effects . Compliance is higher with APAP in subjects reporting any side effect . APAP may be indicated in patients reporting side effects with conventional CPAP Recent objective studies demonstrate relatively low hours of nightly use during nasal continuous positive airway pressure ( CPAP ) therapy for obstructive sleep apnea ( OSA ) . Patients frequently complain of dyspnea or discomfort during CPAP use , especially during expiration ( against the continuous pressure ) , which may be a reason for the low hours of use . We hypothesized that with decreased expiratory pressure , hours of nightly use would increase . Therefore , we r and omized 83 OSA patients to receive either continuous or bilevel positive airway pressure when expiratory pressure is lower . To document objective ly the effective use of either therapy , we built and installed elapsed-time and mask pressure sensors in the patients ' positive airway pressure units . A total of 62 patients were evaluable and followed for 1 yr . Of these , 26 received bilevel and 36 CPAP pressures . The machine timers measured accumulated " machine-on " time , and the mask pressure sensor recorded the total time in which the mask pressure was within 2 cm H2O of the effective pressure ( pressure shown to eliminate 95 % of the obstructive apneas during a full night of polysomnography ) . The mean machine timer hours of CPAP were 5.0 + /- 0.19 SEM and 4.9 + /- 0.23 SEM during bilevel therapy ( p NS ) over a 12-mo period . The pressures required during CPAP or bilevel therapy were not different between high and low hourly users . Effective use , the percentage of time that the machine was running and the prescribed pressure was being delivered , was 80 % in CPAP and 82 % in the bilevel users ( p NS ) . Both groups had equal complaints with regard to mask discomfort , machine noise , and nasal stuffiness . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND AND PURPOSE Quality of life ( QOL ) and sleepiness for patients with sleep apnea/hypopnea syndrome ( SAHS ) might improve with continuous positive airway pressure devices working in auto-adjust mode ( autoCPAP ) by allowing pressure modulations following patient needs . Clinical comparisons between devices driven by different algorithms are needed . METHODS We compared the clinical effectiveness of fixed pressure CPAP and four different autoCPAP devices by assessing compliance and QOL ( 36-item short-form health survey [ SF-36 ] ) . SAHS patients were r and omly allocated to five groups . Polysomnography ( PSG ) was performed to titrate the effective pressure in the constant CPAP group and evaluate residual apnea/hypopnea index ( AHI ) under autoCPAP . Follow-up consisted of clinical visits at three and six months by homecare technicians who assessed compliance , symptom scores and SF-36 scores . A laboratory-based PSG using the same CPAP/autoCPAP device as at home was performed at six months . RESULTS Eighty-three patients ( mean age 56+/-10 yrs ) with mean body mass index ( BMI ) 30.8+/-5.3 kg/m(2 ) and severe SAHS ( mean AHI : 52.3+/-17.8/h ) were included . There were no differences in clinical symptoms or QOL scores , and similar clinical and PSG improvements were seen in all groups . CPAP use was > 5 h per night , without any significant difference between groups . CONCLUSIONS AutoCPAP is equally as effective as fixed CPAP for long-term home treatment in severe SAHS patients Constant continuous positive airway pressure ( CPAP ) is the treatment of choice for the obstructive sleep apnea syndrome ( OSAS ) . To enable the pressure to be matched more accurately to actual requirements , and thus increase patient acceptance , an autoadjusting device based on the measurement of upper airway impedance was developed ( APAP(FOT ) ) . We investigated the efficacy and compliance in continuous use at home . Fifty-two patients were treated ( r and omized crossover ) with CPAP and APAP(FOT ) for 6 wk each . Respiratory disturbances , sleep profile , and arousals improved significantly with both modes ( AHI : baseline , 35.1 + /- 26/h ; APAP(FOT ) , 5.0 + /- 5.2 ; CPAP , 4.3 + /- 6.3 ; p < 0.001 baseline versus each mode ) . The mean pressure with APAP(FOT ) was significantly reduced as compared with CPAP ( CPAP , 7.8 + /- 1.5 cm H2O ; APAP(FOT ) , 5.7 + /- 1.8 cm H2O ; p < 0.001 ) . Under APAP(FOT ) the pressure was lower than that under CPAP for 81.5 + /- 21 % of the time . Although overall use did not differ , 75 % of the patients preferred APAP(FOT ) for home treatment . We conclude that APAP(FOT ) is as efficacious as constant CPAP in the treatment of OSAS . The treatment pressure can be reduced significantly , and sleep microstructure improved with APAP(FOT ) . These might be the reasons for patient preference of automatic therapy STUDY OBJECTIVES Compare auto-adjusting positive airway pressure ( APAP ) treatment with positive airway pressure ( PAP ) titration by polysomnography ( PSG ) followed by CPAP treatment in patients diagnosed with obstructive sleep apnea ( OSA ) by home sleep apnea testing ( HSAT ) . DESIGN Prospect i ve r and omized treatment study . SETTING Tertiary Veterans Administration Medical Center . PARTICIPANTS 156 patients diagnosed with OSA by HSAT ( apneahypopnea index [ AHI ] ≥ 10/h ) suitable for APAP treatment . INTERVENTIONS APAP arm : Treatment with an APAP device , CPAP arm : PSG PAP titration followed by CPAP treatment . MEASUREMENTS Mean PAP adherence , Epworth sleepiness scale ( ESS ) , Functional Outcomes of Sleep Question naire ( FOSQ ) . RESULTS The mean ( ± SD ) age , BMI , and diagnostic AHI ( APAP : 28.6 ± 18.5 , CPAP : 28.3 ± 16.0/h , p = NS ) did not differ between the study arms . After 6 weeks of treatment , 84.6 % of 78 patients started on APAP and 84.3 % of 70 patients started on CPAP ( 8 declined treatment after the titration ) were using PAP , p = NS . The 90 % APAP and level of CPAP were similar ( 10.8 ± 3.1 , 11.7 ± 2.5 cm H2O , p = 0.07 ) . The average nightly PAP use did not differ ( APAP : 4.45 ± 2.3 , CPAP : 4.0 ± 2.3 h , p = NS ) . The improvements in the ESS ( APAP : -4.2 ± 4.7 , CPAP : -3.7 ± 4.8 , p = NS ) and in the FOSQ ( APAP : 2.6 ± 3.5 , CPAP : 2.2 ± 3.7 , p = NS ) were not different . CONCLUSIONS Following diagnosis of OSA by HSAT , treatment with APAP results in equivalent PAP adherence and improvement in sleepiness compared to a PSG titration and CPAP treatment . COMMENTARY A commentary on this article appears in this issue on page 1277 BACKGROUND AND PURPOSE Mouth leak occasionally complicates continuous positive airway pressure ( CPAP ) therapy , which leads to discomfort . While a chinstrap prevents the mouth from opening during sleep , its efficacy in diminishing mouth leak has not been studied . PATIENTS AND METHODS Fifteen patients with mouth leak complaining of mouth dryness and nasal obstruction underwent two consecutive overnight polysomnographies , one with a chinstrap , in r and om order . Cephalometry with and without a chinstrap was r and omly performed on six patients . RESULTS With the chinstrap , both mouth leak and the arousal index decreased significantly , from ( mean+/-SD ) 42.9+/-23.5 to 23.8+/-13.3 % of total sleep time ( TST ) , and from 33.4+/-18.6 to 23.6+/-9.3/sleep hour , respectively . However , snoring time showed a concomitant increase from 6.7+/-14.3 to 24.0+/-13.2 % of TST . The arousal index was significantly higher during leak periods , and its changes correlated positively with changes in mouth leak . Cephalometric measures showed a significant decrease in anterior lower facial height . CONCLUSIONS The chinstrap , by closing the mouth during CPAP , reduces mouth leak and therefore the arousal index in most patients . Nevertheless , the indices remained unacceptably high . The chinstrap may also increase snoring and , in rare cases , can worsen the respiratory disturbance index . Consideration of these potential effects is important before instituting regular home use of the chinstrap OBJECTIVE The efficacy and acceptance of self-regulated continuous positive airway pressure ( auto-CPAP ) ventilation was compared with conventional CPAP administration in the treatment of patients with obstructive sleep apnoea . PATIENTS AND METHODS Using a cross-over design , under polysomnographic monitoring in a sleep laboratory , 25 patients with obstructive sleep apnoea underwent conventional CPAP or auto-CPAP treatment . Using a question naire , patients gave their assessment of its acceptability and efficacy after each treatment session . RESULTS The mean pressure during treatment was the same in the two groups ( 7.2 + /- 1.9 versus 7.1 + /- 1.9 mbar ; no significant difference ) . Maximal pressure during auto-CPAP averaged 3.7 + /- 2.1 mbar higher than during conventional CPAP ventilation . The mean apnoea-hypopnoea index ( AHI ) during auto-CPAP , 4.4 + /- 4.3 mbar , during auto-CPAP was significantly higher than during conventional CPAP treatment ( 2.8 + /- 2.8 mbar ; P = 0.044 ) . In eight patients on auto-CPAP an AHI of 5 or less could not be reached , while an AHI of 5 or less was obtained in all but three patients under conventional CPAP . In a subgroup of 17 patients , in whom a reduction of AHI to at most 5 was achieved with both conventional and auto-CPAP , analysis of sleep pattern and of arousals was similar with the two forms of ventilation . Several patients reported that with auto-CPAP falling in sleep was more difficult and they slept less well . None of the patients preferred auto-CPAP . CONCLUSION By means of the auto-CPAP neither a pressure reduction nor an improvement in compliance could be achieved . Therapeutic effectiveness was significantly less as with conventional CPAP therapy This study is a 12-week r and omized , cross-over , single-blind comparison of the tolerance , compliance , and symptomatic improvement obtained with st and ard nasal continuous positive airway pressure ( CPAP ) vs. an auto-titrating , self-adjusting device ( APAP ) . Sixty newly diagnosed patients , 53 with obstructive sleep apnea ( OSA ) and seven with upper airway resistance syndrome were studied . Thirty-nine patients ( 65 % ) completed the 24-week protocol . Data were complete in 33 . In these 33 patients CPAP and APAP reduced the Epworth Sleepiness score from 15+/-1 ( + /-SEM ) to 8+/-1 and 9+/-1 respectively ( both < 0.0001 from baseline but NS between modes ) . The APAP average pressure was lower than the CPAP pressure , 6.4+/-0.4 and 10.6+/-0.4 cm H20 , respectively . The average daily machine use was greater with APAP , 6.0+/-0.3 hrs . versus 5.5+/-0.3 hrs . with CPAP ( P < 0.04 ) . The number of days of machine use , and the pattern of use were not different between CPAP and APAP . A higher proportion of patients who did not complete the study was r and omized to CPAP for their initial treatment period . This study showed that : 1 ) CPAP and APAP produced an equivalent improvement in daytime sleepiness , 2 ) APAP pressure was lower than CPAP pressure , 3 ) patients wore the APAP device longer during nights they used the pressure support system , and 4 ) patients who began the study with APAP were more prone to continue treatment . We conclude that APAP was better tolerated and used a greater number of hours than CPAP , but the extent of improvement in excessive daytime sleepiness was similar between the two modes of therapy Background : The optimal approach to initiate positive-pressure therapy in patients with obstructive sleep apnea is still debated . Current options are autotitrating positive airway pressure ( APAP ) or manual titration with continuous positive airway pressure ( CPAP ) . Procedures differ by parameters and by algorithms used for adapting pressure . Objectives : To evaluate the efficacy of attended automatic titration in a r and omized crossover study compared with manual titration over 2 nights where the sequence of the titration mode was changed . Therapy outcome was controlled after 6 weeks . Methods : 21 sleep apnea patients were treated using manual CPAP versus automatic APAP titration . The mode used during the 2nd night was continued for 6 weeks . Cardiorespiratory polysomnography , Epworth Sleepiness Scale ( ESS ) , SF-36 score and compliance were assessed . Results : Apnea-hypopnea index reduction was equally effective at similar effective pressure independent of the titration mode . If APAP was applied during the 1st night , total sleep time was longer ( 384 vs. 331 min , p < 0.01 ) and sleep efficacy was higher ( 91 vs. 81 % , p < 0.01 ) than after starting with manual titration with CPAP . Compliance was comparable in both groups ( 4.6 ± 1.9 h ) . The ESS improved in both groups ( from 12.9 to 6.5 ) . SF-36 scores and therapeutic pressure did not much change . Conclusions : Taking the sequence of titration into account , we found equal effectiveness of CPAP and APAP . Sleep quality was better with initial application of APAP – which favors attended automatic titration if only 1 titration night is possible . Both modes are comparable after 6 weeks regarding therapeutic pressure , efficacy , compliance and quality of life STUDY OBJECTIVES ( 1 ) To determine the efficacy of automatically adjusted positive airway pressure ( APAP ) with a comfort feature ( A-Flex ) at reducing apneas and hypopneas in participants with moderate to severe OSA . ( 2 ) To determine the relative difference between A-Flex , continuous positive airway pressure ( CPAP ) , and APAP-derived optimal pressure for CPAP ( CPAP(APAP ) ) on adherence to treatment . ( 3 ) To determine the relative difference between APAP with A-Flex , CPAP , and CPAP(APAP ) on long-term change in functional outcomes . DESIGN R and omized , double-blinded , 3-arm , multicenter trial . SETTING University and Veterans Affairs medical centers . PATIENTS OR PARTICIPANTS 168 participants were r and omized , and 140 completed the 180-day study . INTERVENTIONS ( 1 ) A-Flex ; ( 2 ) CPAP ; ( 3 ) APAP for 14 days and then switched to CPAP at a fixed pressure . MEASUREMENTS AND RESULTS Apnea-hypopnea indices , average and minimum oxygen saturation , time spent < 90 % were significantly poorer for A-Flex vs. CPAP at the initiation of study treatment ; with the exception of minimum oxygen saturation , these differences were absent at 180 days . A-Flex had lower average leak values at both 3 and 6 months . There were no significant differences between groups in major efficacy , adherence , and outcome ( subjective sleepiness , objective vigilance , blood pressure , quality of life ) measures . No differences between groups in attitudes toward use were observed at 3 or 6 months ; participant ratings for CPAP were significantly higher than A-Flex on treatment satisfaction and benefit , but not different for sleep quality and mask comfort . CONCLUSIONS We found that A-Flex shows equivalency , but non-superiority ( except for average leak values ) , in efficacy , adherence , and functional outcomes compared to CPAP after either 3 or 6 months . CLINICAL TRIAL REGISTRY Positive Pressure Treatment of Obstructive Sleep Apnea , http://www . clinical trials.gov , NCT00636181 STUDY OBJECTIVE To determine whether fixed-pressure or variable-pressure CPAP was preferred by patients and gave better outcomes in patients with the obstructive sleep apnea/hypopnea syndrome ( OSAHS ) . DESIGN R and omized blinded cross-over trial with 6 weeks of fixed and 6 weeks of variable-pressure CPAP . SETTING Sleep center . PATIENTS 200 consecutive consenting CPAP naïve patients with daytime sleepiness and > 15 apneas + hypopneas/h after an attended auto-CPAP titration night . INTERVENTIONS CPAP therapy using the same device ( Autoset Spirit ) set for 6 weeks in fixed pressure mode and for 6 weeks in variable pressure mode , the order of therapies being r and omized . MEASUREMENTS AND RESULTS All measurements were recorded at the end of each limb by a research er blind to treatment . These included symptoms , Epworth Score , CPAP usage , objective sleepiness by modified Osler test , vigilance and health related quality of life . A total of 181 of 200 patients completed the study . At the end of the study , patients expressed no significant difference in the primary outcome , patient preference , 72 patients preferring fixed and 69 preferring variable-pressure CPAP . Epworth score was lower on variable ( 9.5 , SEM 0.4 ) than fixed-pressure CPAP ( 10.0 , SEM 0.3 ; P = 0.031 ) . Mean CPAP use was higher on variable ( 4.2 , SEM 0.2 h/night ) than fixed-pressure CPAP ( 4.0 , SEM 0.2 h/night ; P = 0.047 ) . There were no other significant differences between treatments . CONCLUSIONS This study shows no difference in patient preference and only a marginal benefit of variable over fixed-pressure CPAP in OSAHS in terms of subjective sleepiness and CPAP use . The clinical value of this difference remains to be determined . CLINICAL TRIAL INFORMATION Variable-pressure versus fixed-pressure continuous positive airway pressure ( CPAP ) treatment for patients with obstructive sleep apnoea/hypopnoea syndrome ( OSAHS ) ; Registration # IS RCT N43085025.http://www.controlled-trials.com//S RCT N43085025 Previous reports have described compliance with nasal continuous positive airway pressure ( nCPAP ) for the treatment of obstructive sleep apnea ( OSA ) only in terms of the number of patients able to use it beyond their initial trial night or those continuing after some home use . Because of a possible difference between the level of compliance ( mean number of hours of use per 24 h ) needed for symptomatic relief of OSA versus cardiovascular improvement , the level of hourly compliance in chronic nCPAP users may be important . The first part of this study prospect ively examines compliance in a stable population of OSA patients already using nCPAP for 6 months to 2 yr . The second part is a prospect i ve r and omized , crossover study examining the effect of weekly ( three times ) then monthly ( twice ) positive reinforcement on hourly compliance of new nCPAP users for 3 months versus no reinforcement for 3 months . Positive reinforcement consisted of telephone discussion s with the patients about the severity or complications of OSA , benefits of nCPAP , and suggestions about minimizing side effects . Using self- assessment scales , each patient reported the perceived level of improvement from the untreated to the treated condition and the prevalence and severity of side effects from the nCPAP therapy . The level of compliance in stable , chronic nCPAP users with OSA was 6.1 + /- 2.2 h/24 h ( n = 9 ) . For the new nCPAP users during the nonreinforced period , the mean compliance was 6.0 + /- 2.8 h/24 h ; that during the reinforcement period was 6.0 + /- 2.7 h/24 h ( NS ) . There was no significant correlation between perceived improvement in OSA symptoms or between the perceived side effects of nCPAP versus hourly compliance . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Heated humidification can reduce nasal symptoms caused by continuous positive airway pressure ( CPAP ) treatment , but its routine use has not been studied over the medium term in a r and omized controlled trial . The aim of this study is to determine if heated humidification would reduce nasal symptoms and improve adherence with CPAP treatment in all patients with sleep apnoea irrespective of whether they had nasal symptoms initially . METHODS A r and omized , parallel group design . Patients were treated for 3 months with a Fisher & Paykel HC201 pump with built-in heated humidification , or with the heater disabled and without water . Adherence was measured with a timer built into the pumps . Nasal symptoms were measured with a 10-cm visual analogue scale . RESULTS There were 25 in the humidification group and 29 in the non-humidification group . After 12 weeks mean ( st and ard deviation ) adherence with CPAP was 4.7 ( 2.4 ) and 4.5 ( 2.2 ) hours per night respectively . Nasal symptoms that were reduced were nose blocked * 6 ( 12 ) , 18 ( 26 ) ; sneezing * 4 ( 8) , 15 ( 25 ) ; dry nose * 8 ( 12 ) , 24 ( 33 ) ; stuffy nose * 7 ( 14 ) , 22(31 ) ; dry mouth * 13 ( 18 ) , 33(36 ) ; and runny nose * 6 ( 17 ) , 14 ( 29 ) . Parameters marked with an asterisk ' * ' had P < 0.05 with t-tests . CONCLUSION The routine use of heated humidification with CPAP in all patients with sleep apnoea reduced nasal symptoms , but did not improve adherence STUDY OBJECTIVES To determine if auto-adjusting positive airway pressure ( APAP ) would be better tolerated on the basis of delivering a lower mean pressure in patients with mild to moderate obstructive sleep apnoea syndrome ( OSAS ) . DESIGN Patients spent 8 weeks on continuous positive airway pressure ( CPAP ) and 8 weeks on APAP in a r and omized crossover design . SETTING Respiratory Sleep Disorders Unit in a University Hospital and the patient 's home . PARTICIPANTS Twenty-nine patients with newly diagnosed mild to moderate OSAS ( apnoea-hypopnoea frequency of 5 - 30 events/hour ) were studied . INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Overnight polysomnography and Epworth Sleepiness Scale were recorded at baseline and at the end of each treatment period in addition to patient preference for device , side effects , and objective compliance . No differences were found in polysomnographic variables or Epworth Sleepiness Scale scores between the 2 treatment modes , but all variables were significantly improved from baseline values . Mean APAP pressure levels were significantly lower than CPAP ( 6.3 + /- 1.4 vs 8.1 + /- 1.7 cm H2O , p < .001 ) . Patient compliance was similar with both treatments . More patients requiring higher fixed pressure ( > or = 8 cm H2O ) preferred APAP , whereas those requiring lower pressure ( < 8 cm H2O ) preferred CPAP ( p = .03 ) . Follow-up after 18 months of therapy indicated that 76 % of subjects continued to be compliant , with a nightly use of 5.8 + /- 1.9 hours per night , despite high levels of minor side effects . CONCLUSIONS APAP and CPAP are equally effective in managing patients with mild to moderate OSAS , but device preference may be influenced by fixed pressure requirements STUDY OBJECTIVES Positive airway pressure ( PAP ) treatment for obstructive sleep apnea ( OSA ) can be limited by suboptimal compliance . C-Flex technology ( Philips Respironics , PA , USA ) reduces pressure during expiration , aim ing to improve comfort and therefore compliance . This may be of particular relevance to patients requiring high pressures . Many studies thus far have suffered from design limitations and small sample sizes . This study aim ed to compare compliance with C-Flex and CPAP , as well as analyzing objective and subjective sleepiness and vigilance . DESIGN Three-month , double-blinded , parallel-arm r and omized controlled trial . SETTING A university-based sleep laboratory . PATIENTS 76 consecutive patients with severe OSA ( mean + /- SD AHI 60.2 + /- 32.9 events/hour , ESS 13.6 + /- 4.5/24 , BMI 35.6 + /- 7.8 kg/m2 ) , without significant cardiac , respiratory , psychiatric , or sleep comorbidities . INTERVENTIONS Patients were r and omized to C-Flex ( dip level 2 ) or CPAP . MEASUREMENTS AND RESULTS Patients underwent titration with C-Flex/CPAP ( mean pressure 11.6 cm H2O ) . Modified maintenance of wakefulness tests ( mod-MWT ) , psychomotor vigilance tasks ( PVT ) and question naires were administered at baseline and after one and 3 months . Median compliance was 5.51 and 5.89 h/night in the C-Flex and CPAP groups respectively ( P = 0.82 ) . There were no significant differences between groups in terms of PVT reaction time , subjective sleepiness , sleep quality , health-related quality of life , or treatment comfort . There was no significant difference between the groups regarding the change in mod-MWT sleep latency values . CONCLUSIONS In patients with severe OSA both CPAP and C-Flex result ed in substantial improvements in sleepiness , vigilance , and quality of life . The use of C-Flex did not result in greater compliance , and neither treatment appeared superior RATIONALE Obstructive sleep apnea ( OSA ) is a risk factor for cardiovascular death in middle-aged subjects , but it is not known whether it is also a risk factor in the elderly . OBJECTIVES To investigate whether OSA is a risk factor for cardiovascular death and to assess whether continuous positive airway pressure ( CPAP ) treatment is associated with a change in risk in the elderly . METHODS Prospect i ve , observational study of a consecutive cohort of elderly patients ( ≥65 yr ) studied for suspicion of OSA between 1998 and 2007 . Patients with an apnea-hypopnea index ( AHI ) less than 15 were the control group . OSA was defined as mild to moderate ( AHI , 15 - 29 ) or severe ( AHI , ≥30 ) . Patients with OSA were classified as CPAP-treated ( adherence ≥ 4 h/d ) or untreated ( adherence < 4 h/d or not prescribed ) . Participants were monitored until December 2009 . The end point was cardiovascular death . A multivariate Cox survival analysis was used to determine the independent impact of OSA and CPAP treatment on cardiovascular mortality . MEASUREMENTS AND MAIN RESULTS A total of 939 elderly were studied ( median follow-up , 69 mo ) . Compared with the control group , the fully adjusted hazard ratios for cardiovascular mortality were 2.25 ( confidence interval [ CI ] , 1.41 to 3.61 ) for the untreated severe OSA group , 0.93 ( CI , 0.46 to 1.89 ) for the CPAP-treated group , and 1.38 ( CI , 0.73 to 2.64 ) for the untreated mild to moderate OSA group . CONCLUSIONS Severe OSA not treated with CPAP is associated with cardiovascular death in the elderly , and adequate CPAP treatment may reduce this risk STUDY OBJECTIVE To improve adherence to continuous positive airway pressure ( CPAP ) treatment in participants with obstructive sleep apnea ( OSA ) using a cognitive behavioral therapy ( CBT ) intervention . DESIGN A r and omized controlled trial . SETTING A major teaching hospital in Sydney ( 2005 ) . PARTICIPANTS One hundred individuals ( 96 men ) , ranging in age from 32 to 81 years , diagnosed with OSA . INTERVENTION Two 1-hour CBT interventions ( including a video of real CPAP users ) plus treatment as usual ( mask fitting and information ) or treatment as usual only . MEASUREMENTS AND RESULTS Hours of CPAP usage was assessed at 7 nights and 28 nights . Adherence was defined as usage at least 4 hours per night . Question naires measuring self-efficacy , social support , and expectancy ( mediators of adherence ) were given after intervention or after usual treatment . A higher adherence to CPAP therapy was found in the CBT group ( 2.9 hours difference ) relative to treatment as usual ( P < 0.001 ) at 28 days . Only 4 participants in the CBT group did not initiate treatments after their titration study , compared with 15 in the treatment as usual group ( P < 0.02 ) . The CBT group had significantly higher scores for self-efficacy ( P < 0.001 ) and social support P < 0.008 ) but not for expectancy . CONCLUSIONS The CBT intervention result ed in both increased adherence and " uptake " of CPAP and therefore would be expected to reduce the social , economic , and health-related consequences of untreated OSA Rationale Despite a significant association between obesity hypoventilation syndrome ( OHS ) and cardiac dysfunction , no r and omised trials have assessed the impact of non-invasive ventilation ( NIV ) or CPAP on cardiac structure and function assessed by echocardiography . Objectives We performed a secondary analysis of the data from the largest multicentre r and omised controlled trial of OHS ( Pickwick project , n=221 ) to determine the comparative efficacy of 2 months of NIV ( n=71 ) , CPAP ( n=80 ) and lifestyle modification ( control group , n=70 ) on structural and functional echocardiographic changes . Methods Conventional transthoracic two-dimensional and Doppler echocardiograms were obtained at baseline and after 2 months . Echocardiographers at each site were blinded to the treatment arms . Statistical analysis was performed using intention-to-treat analysis . Results At baseline , 55 % of patients had pulmonary hypertension and 51 % had evidence of left ventricular hypertrophy . Treatment with NIV , but not CPAP , lowered systolic pulmonary artery pressure ( −3.4 mm Hg , 95 % CI −5.3 to –1.5 ; adjusted P=0.025 vs control and P=0.033 vs CPAP ) . The degree of improvement in systolic pulmonary artery pressure was greater in patients treated with NIV who had pulmonary hypertension at baseline ( −6.4 mm Hg , 95 % CI −9 to –3.8 ) . Only NIV therapy decreased left ventricular hypertrophy with a significant reduction in left ventricular mass index ( −5.7 g/m2 ; 95 % CI −11.0 to –4.4 ) . After adjusted analysis , NIV was superior to control group in improving left ventricular mass index ( P=0.015 ) . Only treatment with NIV led to a significant improvement in 6 min walk distance ( 32 m ; 95 % CI 19 to 46 ) . Conclusion In patients with OHS , medium-term treatment with NIV is more effective than CPAP and lifestyle modification in improving pulmonary hypertension , left ventricular hypertrophy and functional outcomes . Long-term studies are needed to confirm these results . Trial registration number Pre- results , NCT01405976 ( https:// clinical trials.gov/ ) Objectives / Background Improving adherence to CPAP devices is crucial to reduce the long-term morbidity associated with OSA . SensAwake is a unique pressure relief technology that aims to promptly reduce the pressure upon sensing irregular respiration indicative of wakefulness . The purpose of this study was to compare adherence and sleep- quality outcomes in patients treated by CPAP with and without SensAwake technology . Methods Participants with moderate-to-severe OSA were r and omized to use CPAP devices with or without SensAwake ( 4 weeks ) before crossing over . Results Sixty-five patients completed both arms of the trial . There were no statistically significant differences in CPAP adherence with or without SensAwake over the study period ( SensAwake ON 272.67 ± 17.06 versus SensAwake OFF 289.09 ± 15.24 ; p = 0.180 ) . SensAwake reported a significantly lower system leak , 90th percentile leak , and time spent with excessive ( > 60 L/min ) leak . Subgroup analysis suggested a trend towards improved adherence in patients with moderate-to-severe insomnia when using SensAwake . Conclusions Using SensAwake incurred benefit in terms of reduced leaks ; however , SensAwake did not improve CPAP adherence or objective sleep quality . Further studies should investigate the accuracy of observed trends towards increased adherence using SensAwake among patients with OSA and insomnia BACKGROUND Many patients with sleep apnoea/hypopnoea syndrome ( SAHS ) find nasal continuous positive airway pressure ( CPAP ) treatment unsatisfactory due to side effects related to mouth air leakage . A study was performed to compare side effects with face mask and nose mask CPAP therapy in patients with SAHS , with and without uvulopalatopharyngoplasty ( U3P ) . METHODS Twenty newly diagnosed patients with SAHS took part in a r and omised double limb trial of face or nose mask CPAP therapy ( four weeks per limb ) in which CPAP compliance in terms of machine run time was measured and patients answered a symptom question naire on side effects result ing from the mask . Ten patients with SAHS with U3P ( SAHS/U3P ) who were already regular users of nasal CPAP were also given a four week trial of face mask CPAP to compare compliance and symptoms . Ten patients with SAHS were matched with the 10 SAHS/U3P patients for body mass index , age , apnoea/hypopnoea index , and CPAP pressure . Long term compliance was estimated one year after the mask comparison studies . RESULTS For patients with SAHS nightly compliance was higher with a nose mask ( mean ( SE ) 5.3 ( 0.4 ) hours/night CPAP ) than with a face mask ( 4.3 ( 0.5 ) hours/night CPAP ) , p = 0.01 ( mean difference 1.0 hour/night , 95 % CI 1.8 to 0.3 ) . Nose masks were rated more comfortable by 19 of 20 patients ( p<0.001 ) despite more mouth leak related symptoms . For SAHS/U3P patients compliance was marginally higher with nose masks ( 5.1 ( 0.7 ) hours/night CPAP ) than with face masks ( 4.0 ( 0.8 ) hours/night CPAP ) , p = 0.07 ( mean difference 1.1 hour/night , 95 % CI 2.1 to 0.1 ) . Nose masks were rated more comfortable by seven of 10 patients . There were no significant differences in side effect scores with face and nose masks . At one year nine of 10 SAHS patients and nine of 10 SAHS/U3P patients were still using CPAP . Compliance was 5.4 ( 0.6 ) hours/night for the SAHS patients and 3.5 ( 0.4 ) hours/night for the SAHS/U3P patients , p = 0.02 ( mean difference 1.9 hour/night , 95 % CI 3.6 to 0.3 ) . CONCLUSIONS Compliance is greater with nose mask CPAP than with face mask CPAP because the overall comfort is better and compensates for increased symptoms associated with mouth leakage . Improved face mask design is needed BACKGROUND Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep . Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support . To date there have been no long-term trials comparing these treatment modalities . We therefore aim ed to determine the long-term comparative effectiveness of both treatment modalities . METHODS We did a multicentre , open-label , r and omised controlled trial at 16 clinical sites in Spain . We included patients aged 15 - 80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We r and omly assigned patients , using simple r and omisation through an electronic data base , to receive treatment with either non-invasive ventilation or continuous positive airway pressure . Both investigators and patients were aware of the treatment allocation . The research team was not involved in deciding hospital treatment , duration of treatment in the hospital , and adjustment of medications , as well as adjudicating cardiovascular events or cause of mortality . Treating clinicians from the routine care team were not aware of the treatment allocation . The primary outcome was the number of hospitalisation days per year . The analysis was done according to the intention-to-treat principle . This study is registered with Clinical Trials.gov , number NCT01405976 . FINDINGS From May 4 , 2009 , to March 25 , 2013 , 100 patients were r and omly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group , of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis . The median follow-up was 5·44 years ( IQR 4·45 - 6·37 ) for all patients , 5·37 years ( 4·36 - 6·32 ) in the continuous positive airway pressure group , and 5·55 years ( 4·53 - 6·50 ) in the non-invasive ventilation group . The mean hospitalisation days per patient-year were 1·63 ( SD 3·74 ) in the continuous positive airway pressure group and 1·44 ( 3·07 ) in the non-invasive ventilation group ( adjusted rate ratio 0·78 , 95 % CI 0·34 - 1·77 ; p=0·561 ) . Adverse events were similar between both groups . INTERPRETATION In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea , non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness . Given that continuous positive airway pressure has lower complexity and cost , continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available . FUNDING Instituto de Salud Carlos III , Spanish Respiratory Foundation , and Air Liquide Spain Introduction Obstructive sleep apnoea ( OSA ) is a prevalent disease associated with cardiovascular events . Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events . Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes , result ing in sympathetic overactivity and blood pressure ( BP ) elevation . Continuous positive airway pressure ( CPAP ) is the primary treatment for OSA and induces a small but significant reduction in BP . The use of auto-adjusting positive airway pressure ( APAP ) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities . However , the pathophysiological mechanisms implicated are not fully eluci date d. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP . Therefore , this double-blind r and omised controlled trial aims to compare muscle sympathetic nerve activity ( MSNA ) assessed by microneurography ( reference method for measuring sympathetic activity ) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients . This present manuscript describes the design of our study , no results are presented herein . and is registered under the below reference number . Methods and analysis Adult subjects with newly diagnosed OSA ( Apnoea – Hypopnoea Index > 20/hour ) will be r and omised for treatment with APAP or fixed CPAP . Measurements of sympathetic activity by MSNA , heart rate variability and catecholamines will be obtained at baseline and after 30 days . The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats . Sample size calculation was performed with bilateral assumption . We will use the Student ’s t-test to compare changes in sympathetic tone between groups . Ethics and dissemination The protocol was approved by The French Regional Ethics Committee . The study started in March 2018 with primary completion expected to March 2019 . Dissemination plans of the results include presentations at conferences and publication in peer- review ed journals . Trial registration number NCT03428516 ; Pre- results BACKGROUND Obstructive sleep apnea is associated with an increased risk of cardiovascular events ; whether treatment with continuous positive airway pressure ( CPAP ) prevents major cardiovascular events is uncertain . METHODS After a 1-week run-in period during which the participants used sham CPAP , we r and omly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care ( CPAP group ) or usual care alone ( usual-care group ) . The primary composite end point was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for unstable angina , heart failure , or transient ischemic attack . Secondary end points included other cardiovascular outcomes , health-related quality of life , snoring symptoms , daytime sleepiness , and mood . RESULTS Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness . In the CPAP group , the mean duration of adherence to CPAP therapy was 3.3 hours per night , and the mean apnea-hypopnea index ( the number of apnea or hypopnea events per hour of recording ) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up . After a mean follow-up of 3.7 years , a primary end-point event had occurred in 229 participants in the CPAP group ( 17.0 % ) and in 207 participants in the usual-care group ( 15.4 % ) ( hazard ratio with CPAP , 1.10 ; 95 % confidence interval , 0.91 to 1.32 ; P=0.34 ) . No significant effect on any individual or other composite cardiovascular end point was observed . CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood . CONCLUSIONS Therapy with CPAP plus usual care , as compared with usual care alone , did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease . ( Funded by the National Health and Medical Research Council of Australia and others ; SAVE Clinical Trials.gov number , NCT00738179 ; Australian New Zeal and Clinical Trials Registry number , ACTRN12608000409370 . ) Background The obstructive sleep apnoea syndrome ( OSAS ) is conventionally treated by continuous positive airway pressure set at a fixed level ( fCPAP ) . Automatic mask pressure adjustment ( autoCPAP ) is increasingly used during home therapy . We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term . Methods In this multicentre equivalence trial , 208 patients with OSAS , with median Epworth sleepiness score ( ESS ) 13 , apnoea/hypopnoea index 48.4/hour , were r and omised to treatment with autoCPAP ( 5–15 mbar ) or fCPAP ( pressure set at the 90th percentile applied by autoCPAP during 2–4 weeks adaptation ) . Co primary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment . Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals . Results At 2 years , in the intention to treat analysis , the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP ( n=113 , mean ESS-change −6.3 , 95 % CI −7.1 to −5.5 ; sleep resistance time + 8.3 min , + 6.9 to + 9.7 ) and fCPAP ( n=95 , mean ESS-change −6.2 , 95 % CI −7.0 to −5.3 ; sleep resistance time + 6.3 min , + 4.7 to + 7.8 ) . The 95 % CI of difference in ESS-reduction between autoCPAP and fCPAP was −0.9 to + 1.4 and the 95 % CI of difference in increase in sleep resistance time was −2.6 to + 1.0 min . Blood pressure reduction and OSAS-related costs were similar between groups . Conclusions AutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years . Costs of these treatments are similar . Trial registration number Clinical Trials.gov NCT00280800 |
2,126 | 24,692,581 | Our results support the existence of detrimental effects of smoking on survival also after CRC diagnosis . | Smoking is a risk factor for colorectal cancer ( CRC ) incidence and mortality .
However , little is known on smoking and its association with survival after CRC diagnosis .
We conducted a systematic review and meta- analysis to summarize current evidence . | The effect of smoking on survival in cancer patients is limited by the lack of structured prospect i ve assessment s of smoking at diagnosis . To assess the effect of smoking at diagnosis on survival , structured smoking assessment s were obtained in a cohort of 5,185 cancer patients within 30 days of a cancer diagnosis between 1982 and 1998 . Hazard ratios ( HRs ) or odds ratios were generated to analyze the effects of smoking at diagnosis on overall mortality ( OM ) and disease‐specific mortality ( DSM ) in a patient cohort from 13 disease sites containing at least 100 patients in each disease site . With a minimum of 12 years of follow‐up , current smoking increased OM risk versus recent quit ( HR 1.17 ) , former ( HR 1.29 ) and never smokers ( HR 1.38 ) in the overall cohort . Current smoking increased DSM risk versus former ( HR 1.23 ) and never smokers ( HR 1.18 ) . In disease sites with proportionately large ( > 20 % ) recent quit cohorts ( lung and head/neck ) , current smoking increased OM and DSM risks as compared with recent quit . Current smoking increased mortality risks in lung , head/neck , prostate and leukemia in men and breast , ovary , uterus and melanoma in women . Current smoking was not associated with any survival benefit in any disease site . Data using prospect i ve structured smoking assessment s demonstrate that current smoking increased long‐term OM and DSM . St and ardized smoking assessment at diagnosis is an important variable for evaluating outcomes in cancer patients Background : It is increasingly recognised that host-related factors may be important in determining cancer outcome . The aim was to examine the relationship between patient physiology , the systemic inflammatory response and survival after colorectal cancer resection . Methods : Patients undergoing potentially curative resection of colorectal cancer were identified from a prospect ively maintained data base . Patient physiology was assessed using the physiological and operative severity score for the enumeration of mortality and morbidity ( POSSUM ) criteria . The systemic inflammatory response was assessed using the modified Glasgow Prognostic Score ( mGPS ) . Multivariate 5-year survival analysis was carried out with calculation of hazard ratios ( HR ) . Results : A total of 320 patients were included . During follow-up ( median 74 months ) , there were 136 deaths : 83 colorectal cancer related and 53 non-cancer related . Independent predictors of cancer-specific survival were age ( HR : 1.46 , P<0.01 ) , Dukes stage ( HR : 2.39 , P<0.001 ) , mGPS ( HR : 1.78 , P<0.001 ) and POSSUM physiology score ( HR : 1.38 , P=0.02 ) . Predictors of overall survival were age ( HR : 1.64 , P<0.001 ) , smoking ( HR : 1.52 , P=0.02 ) , Dukes stage ( HR : 1.64 , P<0.001 ) , mGPS ( HR : 1.60 , P<0.001 ) and POSSUM physiology score ( HR : 1.27 , P=0.03 ) . A relationship between mGPS and POSSUM physiology score was also established ( P<0.006 ) . Conclusion : The POSSUM physiology score and the systemic inflammatory response are strongly associated and both are independent predictors of cancer specific and overall survival in patients undergoing potentially curative resection of colorectal cancer BACKGROUND Cigarette smoking is an established risk factor for colorectal cancer . Because colorectal carcinogenesis is a heterogeneous process , we investigated whether cigarette smoking is differentially associated with molecularly defined subtypes of colorectal cancer . METHODS We evaluated associations between smoking and incident colorectal cancer , overall and by microsatellite instability ( MSI ) phenotype ( MSI-high vs MSI-low or microsatellite stable ) , CpG isl and methylator phenotype ( CIMP positive or CIMP negative ) , and BRAF mutation status ( BRAF mutation positive or BRAF mutation negative ) , among 37 399 participants in a population -based cohort study ( the Iowa Women 's Health Study ) . Cigarette smoking ( and other exposures ) was assessed by self-report at baseline in 1986 , including smoking status ( never and ever [ former or current ] ) , age at initiation , total duration , average number of cigarettes smoked per day , cumulative pack-years , and induction period . Vital status and state of residence were determined by mailed follow-up question naires in 1987 , 1989 , 1992 , and 1997 and by linkage to Iowa death certificate records . Nonrespondents were checked via the National Death Index to identify descendants . Participants with newly diagnosed ( ie , incident ) colorectal cancer were identified through annual linkage with the Iowa Cancer Registry . Archived paraffin-embedded tumor tissue specimens were obtained for 555 patients with colorectal cancer who were diagnosed from January 1 , 1986 , through December 31 , 2002 , and MSI status , CIMP status , and BRAF status were determined . Multivariable Cox regression models were fit to estimate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . RESULTS Ever-smokers were at moderately increased risk for incident colorectal cancer ( RR = 1.19 , 95 % CI = 1.05 to 1.35 ) compared with never-smokers . Higher risk estimates were observed for current smokers with MSI-high tumors ( RR = 1.99 , 95 % CI = 1.26 to 3.14 ) , CIMP-positive tumors ( RR = 1.88 , 95 % CI = 1.22 to 2.90 ) , and BRAF mutation-positive tumors ( RR = 1.92 , 95 % CI = 1.22 to 3.02 ) . Other smoking-related variables ( ie , age at initiation , total duration , average number of cigarettes smoked per day , cumulative pack-years , and induction period ) were also associated with MSI-high , CIMP-positive , and BRAF mutation-positive tumor subtypes . Conversely , cigarette smoking status ( ever vs never ) was not associated with the MSI-low or microsatellite stable ( RR = 1.00 , 95 % CI = 0.79 to 1.25 ) , CIMP-negative ( RR = 1.02 , 95 % CI = 0.81 to 1.30 ) , or BRAF mutation-negative subtypes ( RR = 1.00 , 95 % CI = 0.65 to 1.27 ) . CONCLUSIONS In this prospect i ve study of older women , cigarette smoking was associated with the MSI-high , CIMP-positive , and BRAF mutation-positive colorectal cancer subtypes , which indicates that epigenetic modification may be functionally involved in smoking-related colorectal carcinogenesis PURPOSE By using data from North Central Cancer Treatment Group Phase III Trial N0147 , a r and omized adjuvant trial of patients with stage III colon cancer , we assessed the relationship between smoking and cancer outcomes , disease-free survival ( DFS ) , and time to recurrence ( TTR ) , accounting for heterogeneity by patient and tumor characteristics . PATIENTS AND METHODS Before r and om assignment to infusional fluorouracil , leucovorin , and oxaliplatin ( FOLFOX ) or FOLFOX plus cetuximab , 1,968 participants completed a question naire on smoking history and other risk factors . Cox models assessed the association between smoking history and the primary trial outcome of DFS ( ie , time to recurrence or death ) , as well as TTR , adjusting for other clinical and patient factors . The median follow-up was 3.5 years among patients who did not experience events . RESULTS Compared with never-smokers , ever smokers experienced significantly shorter DFS ( 3-year DFS proportion : 70 % v 74 % ; hazard ratio [ HR ] , 1.21 ; 95 % CI , 1.02 to 1.42 ) . This association persisted after multivariate adjustment ( HR , 1.23 ; 95 % CI , 1.02 to 1.49 ) . There was significant interaction in this association by BRAF mutation status ( P = .03 ) : smoking was associated with shorter DFS in patients with BRAF wild-type ( HR , 1.36 ; 95 % CI , 1.11 to 1.66 ) but not BRAF mutated ( HR , 0.80 ; 95 % CI , 0.50 to 1.29 ) colon cancer . Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer ( HR , 1.50 [ 95 % CI , 1.12 to 2.00 ] v HR , 1.09 [ 95 % CI , 0.85 to 1.39 ] ) , although interaction by KRAS mutation status was not statistically significant ( P = .07 ) . Associations were comparable in analyses of TTR . CONCLUSION Overall , smoking was significantly associated with shorter DFS and TTR in patients with colon cancer . These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer |
2,127 | 29,027,128 | Conclusions CI of beta-lactam antibiotics is associated with better cure rates and higher % fT > MIC when administered to critically ill patients with respiratory infections , but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections | Background Critically ill patients display altered pharmacokinetics and pharmacodynamics and are more likely to be infected with more resistant pathogens .
Beta-lactam antibiotics exhibit time-dependent pharmacodynamics ; therefore , it is postulated that continuous infusion ( CI ) may optimize these parameters .
Objective To perform a systematic review and meta- analysis of the available literature comparing CI versus intermittent bolus ( IB ) of beta-lactam antibiotics in critically ill adult patients with respiratory infections to determine if clinical benefits exist . | A prospect i ve , r and omized pilot study was undertaken to compare the efficacy of continuous versus intermittent ceftazidime in ICU patients with nosocomial pneumonia . Ceftazidime was administered either as a 3 g/day continuous infusion ( CI ) or an intermittent infusion ( II ) of 2 g every 8 h. In addition , all patients received concomitant once-daily tobramycin . The demographics of the evaluable patients ( n = 35 ) were similar between the groups : age ( years ) , CI 46 + /- 16 , II 56 + /- 20 ; Apache score , CI 14 + /- 4 , II 16 + /- 6 ; time ( days ) from admission to diagnosis , CI 9 + /- 6 , II 9 + /- 6 . Clinical efficacy , defined as cure/improvement was similar between groups [ n ( % ) , CI 16/17 ( 94 ) , II 15/18 ( 83 ) ] , while microbiological response was also comparable [ n ( % ) , CI 10/13 ( 76 ) , II 12/15 ( 80 ) ] . Minimal inhibitory concentrations ( MICs ) for all isolates were measured throughout the treatment course ; there was no development of resistance during therapy for either regimen . While limited clinical data exist , our results suggest that the use of ceftazidime by CI administration maintains clinical efficacy , optimizes the pharmacodynamic profile and uses less antibiotic compared with the st and ard 2 g every 8 h intermittent dosing regimen The extreme pharmacokinetic behaviour of drugs sometimes observed in critically ill patients poses a significant threat to the achievement of optimal antibiotic treatment outcomes . Scant information on beta-lactam antibiotic therapeutic drug monitoring ( TDM ) is available . The objective of this prospect i ve study was to evaluate the practicality and utility of a beta-lactam TDM programme in critically ill patients . TDM was performed twice weekly on all eligible patients at a 30-bed tertiary referral critical care unit . Blood concentrations were determined by fast-throughput high-performance liquid chromatography ( HPLC ) assays and were available within 12h of sampling . Dose adjustment was instituted if the trough or steady-state blood concentration was below 4 - 5x the minimum inhibitory concentration ( MIC ) or above 10x MIC . A total of 236 patients were subject to TDM over an 11-month period . The mean+/-st and ard deviation age was 53.5+/-18.3 years . Dose adjustment was required in 175 ( 74.2 % ) of the patients , with 119 of these patients ( 50.4 % ) requiring dose increases after the first TDM . For outcome of therapy , 206 ( 87.3 % ) courses result ed in a positive treatment outcome and there were 30 ( 12.7 % ) treatment failures observed including 14 deaths and 15 courses requiring escalation to broader-spectrum agents ; 1 course was ceased due to an adverse drug reaction . Using binomial logistic regression , only an elevated Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ( P<0.01 ) and elevated plasma creatinine concentration ( P=0.05 ) were found to be predictive of mortality . In conclusion , further research is required to determine definitively whether achievement of optimal beta-lactam pharmacodynamic targets improves clinical outcomes Introduction Meropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration of pathogens . The goal of this study was to compare clinical and bacteriological efficacy of continuous meropenem infusion versus bolus administration in critically ill patients with severe infection , and to evaluate the safety of both dosing regimens . Methods Patients admitted to the interdisciplinary Intensive Care Unit ( ICU ) who suffered from severe infections and received meropenem were r and omized either in the Infusion group ( n = 120 ) or in the Bolus group ( n = 120 ) . Patients in the Infusion group received a loading dose of 2 g of meropenem followed by a continuous infusion of 4 g of meropenem over 24 hours . Patients in the Bolus group were given 2 g of meropenem over 30 minutes every 8 hours . Clinical and microbiological outcome , safety , meropenem-related length of ICU and hospital stay , meropenem-related length of mechanical ventilation , duration of meropenem treatment , total dose of meropenem , and ICU and in-hospital mortality were assessed . Results Clinical cure at the end of meropenem therapy was comparable between both groups ( 83.0 % patients in the Infusion vs. 75.0 % patients in the Bolus group ; P = 0.180 ) . Microbiological success rate was higher in the Infusion group as opposed to the Bolus group ( 90.6 % vs. 78.4 % ; P = 0.020 ) . Multivariate logistic regression identified continuous administration of meropenem as an independent predictor of microbiological success ( OR = 2.977 ; 95 % CI = 1.050 to 8.443 ; P = 0.040 ) . Meropenem-related ICU stay was shorter in the Infusion group compared to the Bolus group ( 10 ( 7 to 14 ) days vs. 12 ( 7 to 19 ) days ; P = 0.044 ) as well as shorter duration of meropenem therapy ( 7 ( 6 to 8) days vs. 8 ( 7 to 10 ) days ; P = 0.035 ) and lower total dose of meropenem ( 24 ( 21 to 32 ) grams vs. 48 ( 42 to 60 ) grams ; P < 0.0001 ) . No severe adverse events related to meropenem administration in either group were observed . Conclusions Continuous infusion of meropenem is safe and , in comparison with higher intermittent dosage , provides equal clinical outcome , generates superior bacteriological efficacy and offers encouraging alternative of antimicrobial therapy in critically ill patients See related commentary by De Waele and Carlier , http://ccforum.com/content/17/2/130 Introduction Improved methods to optimize drug dosing in the critically ill are urgently needed . Traditional prescribing culture involves recognition of factors that m and ate dose reduction ( such as renal impairment ) , although optimizing drug exposure , through more frequent or augmented dosing , represents an evolving strategy . Elevated creatinine clearance ( CLCR ) has been associated with sub-therapeutic antibacterial concentrations in the critically ill , a concept termed augmented renal clearance ( ARC ) . We aim ed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients , while also examining demographic , physiological and illness severity characteristics that may help identify this phenomenon . Methods This prospect i ve observational study was performed in a 30-bed tertiary level , university affiliated , adult intensive care unit . Consecutive traumatized and septic critically ill patients , receiving antibacterial therapy , with a plasma creatinine concentration ≤110 μmol/L , were eligible for enrolment . Pulse contour analysis ( Vigileo / Flo Trac ® system , Edwards Lifesciences , Irvine , CA , USA ) , was used to provide continuous cardiac index ( CI ) assessment over a single six-hour dosing interval . Urinary CLCR measures were obtained concurrently . Results Seventy-one patients contributed data ( sepsis n = 43 , multi-trauma n = 28 ) . Overall , 57.7 % of the cohort manifested ARC , although there was a greater prevalence in trauma ( 85.7 % versus 39.5 % , P < 0.001 ) . In all patients , a weak correlation was noted between CI and CLCR ( r = 0.346 , P = 0.003 ) . This was mostly driven by septic patients ( r = 0.508 , P = 0.001 ) , as no correlation ( r = -0.012 , P = 0.951 ) was identified in trauma . Those manifesting ARC were younger ( P<0.001 ) , male ( P = 0.012 ) , with lower acute physiology and chronic health evaluation ( APACHE ) II ( P= 0.008 ) and modified sequential organ failure assessment ( SOFA ) scores ( P = 0.013 ) , and higher cardiac indices ( P = 0.013 ) . In multivariate analysis , age ≤50 years , trauma , and a modified SOFA score ≤4 , were identified as significant risk factors . These had greater utility in predicting ARC , compared with CI assessment alone . Conclusions Diagnosis , illness severity and age , are likely to significantly influence renal drug elimination in the critically ill , and must be regularly considered in future study design and daily prescribing practice BACKGROUND Beta-lactam antibiotics are a commonly used treatment for severe sepsis , with intermittent bolus dosing st and ard therapy , despite a strong theoretical rationale for continuous administration . The aim of this trial was to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe sepsis . METHODS This was a prospect i ve , double-blind , r and omized controlled trial of continuous infusion versus intermittent bolus dosing of piperacillin-tazobactam , meropenem , and ticarcillin-clavulanate conducted in 5 intensive care units across Australia and Hong Kong . The primary pharmacokinetic outcome on treatment analysis was plasma antibiotic concentration above the minimum inhibitory concentration ( MIC ) on days 3 and 4 . The assessed clinical outcomes were clinical response 7 - 14 days after study drug cessation , ICU-free days at day 28 and hospital survival . RESULTS Sixty patients were enrolled with 30 patients each allocated to the intervention and control groups . Plasma antibiotic concentrations exceeded the MIC in 82 % of patients ( 18 of 22 ) in the continuous arm versus 29 % ( 6 of 21 ) in the intermittent arm ( P = .001 ) . Clinical cure was higher in the continuous group ( 70 % vs 43 % ; P = .037 ) , but ICU-free days ( 19.5 vs 17 days ; P = .14 ) did not significantly differ between groups . Survival to hospital discharge was 90 % in the continuous group versus 80 % in the intermittent group ( P = .47 ) . CONCLUSIONS Continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure . This study provides a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints The st and ard mode of administration of piperacillin treatment is by intermittent infusion . However , continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity . In previous studies , we found a higher rate of clinical cure of ventilator-associated pneumonia ( VAP ) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime . Therefore , the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam ( PIP/TAZ ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure . Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration ( MIC ) of 8 microg/mL [ 8/9 ( 88.9 % ) vs. 6/15 ( 40.0 % ) ; odds ratio (OR)=10.79 , 95 % confidence interval ( CI ) 1.01 - 588.24 ; P=0.049 ] or 16 microg/mL [ 7/8 ( 87.5 % ) vs. 1/6 ( 16.7 % ) ; OR=22.89 , 95 % CI 1.19 - 1880.78 ; P=0.03 ] . Thus , administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8 - 16 microg/mL in patients without renal failure Augmented renal clearance ( ARC ) is known to influence β-lactam antibiotic pharmacokinetics . This sub study of the BLING-II trial aim ed to explore the association between ARC and patient outcomes in a large r and omised clinical trial . BLING-II enrolled 432 participants with severe sepsis r and omised to receive β-lactam therapy by continuous or intermittent infusion . An 8-h creatinine clearance ( CLCr ) measured on Day 1 was used to identify ARC , defined as CLCr ≥ 130 mL/min . Patients receiving any form of renal replacement therapy were excluded . Primary outcome was alive ICU-free days at Day 28 . Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation . A total of 254 patients were included , among which 45 ( 17.7 % ) manifested ARC [ median ( IQR ) CLCr 165 ( 144 - 198 ) mL/min ] . ARC patients were younger ( P < 0.001 ) , more commonly male ( P = 0.04 ) and had less organ dysfunction ( P < 0.001 ) . There was no difference in ICU-free days at Day 28 [ ARC , 21 ( 12 - 24 ) days ; no ARC , 21 ( 11 - 25 ) days ; P = 0.89 ] , although clinical cure was significantly greater in the unadjusted analysis in those manifesting ARC [ 33/45 ( 73.3 % ) vs. 115/209 ( 55.0 % ) P = 0.02 ] . This was attenuated in the multivariable analysis . No difference was noted in 90-day mortality . There were no statistically significant differences in clinical outcomes in ARC patients according to the dosing strategy employed . In this sub study of a large clinical trial of β-lactam antibiotics in severe sepsis , ARC was not associated with any differences in outcomes , regardless of dosing strategy The pharmacodynamics and pharmacokinetics of ceftazidime administered by continuous infusion and intermittent bolus over a 4-day period were compared . We conducted a prospect i ve , r and omized , crossover study of 12 critically ill patients with suspected gram-negative infections . The patients were r and omized to receive ceftazidime either as a 2-g intravenous ( i.v . ) loading dose followed by a 3-g continuous infusion ( CI ) over 24 h or as 2 g i.v . every 8 h ( q8h ) , each for 2 days . After 2 days , the patients were crossed over and received the opposite regimen . Each regimen also included tobramycin ( 4 to 7 mg/kg of body weight , given i.v . q24h ) . Eighteen blood sample s were drawn on study days 2 and 4 to evaluate the pharmacokinetics of ceftazidime and its pharmacodynamics against a clinical isolate of Pseudomonas aeruginosa ( R288 ) . The patient demographics ( means + /- st and ard deviations ) were as follows : age , 57 + /- 12 years ; sex , nine males and three females ; APACHE II score , 15 + /- 3 ; diagnosis , 9 of 12 patients with pneumonia . The mean pharmacokinetic parameters for ceftazidime given as an intermittent bolus ( IB ) ( means + /- st and ard deviations ) were as follows : maximum concentration of drug in serum , 124.4 + /- 52.6 micrograms/ml ; minimum concentration in serum , 25.0 + /- 17.5 micrograms/ml ; elimination constant , 0.268 + /- 0.205 h-1 ; half-life , 3.48 + /- 1.61 h ; and volume of distribution , 18.9 + /- 9.0 liters . The steady-state ceftazidime concentration for CI was 29.7 + /- 17.4 micrograms/ml , which was not significantly different from the targeted concentrations . The range of mean steady-state ceftazidime concentrations for the 12 patients was 10.6 to 62.4 micrograms/ml . Tobramycin peak concentrations ranged between 7 and 20 micrograms/ml . As expected , the area under the curve for the 2-g q8h regimen was larger than that for CI ( P = 0.003 ) . For IB and CI , the times that the serum drug concentration was greater than the MIC were 92 and 100 % , respectively , for each regimen against the P. aeruginosa clinical isolate . The 24-h bactericidal titers in serum , at which the tobramycin concentrations were < 1.0 microgram/ml in all patients , were the same for CI and IB ( 1:4 ) . In the presence of tobramycin , the area under the bactericidal titer-time curve ( AUBC ) was significantly greater for IB than CI ( P = 0.001 ) . After tobramycin was removed from the serum , no significant difference existed between the AUBCs for CI and IB . We conclude that CI of ceftazidime utilizing one-half the IB daily dose was equivalent to the IB treatment as judged by pharmacodynamic analysis of critically ill patients with suspected gram-negative infections . No evaluation comparing the clinical efficacies of these two dosage regimens was performed ABSTRACT Beta-lactams are regularly administered in intermittent short-term infusions . The percentage of the dosing interval during which free drug concentrations exceed the MIC ( fT > MIC ) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams . Therefore , administration by continuous infusion has gained increasing interest recently . We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose , compared to the st and ard regimen of intermittent short-term infusion , results in a superior probability of target attainment as assessed by the fT > MIC value of imipenem . In this prospect i ve , r and omized , controlled clinical study , patients received either a loading dose of 1 g/1 g imipenem and cilastatin ( as a short-term infusion ) at time zero , followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days ( n = 10 ) , or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days ( total daily dose , 3 g/3 g ; n = 10 ) . Imipenem concentrations in plasma were determined by using a vali date d liquid chromatography-t and em mass spectrometry assay . A two-compartment open model was employed for population pharmacokinetic modeling . We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40 % fT > MIC . The probability of target attainment by MIC for intermittent infusion was robust ( > 90 % ) up to MICs of 1 to 2 mg/liter . The corresponding value for continuous infusion was 2 to 4 mg/liter . Although all 20 patients had an fT > MIC of 100 % , 3 patients died . Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis . Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients Since the bactericidal effects of beta-lactam antibiotics are time dependent , the optimum strategy for their administration could be continuous infusion . In this prospect i ve , r and omised controlled trial to evaluate the clinical efficacy of continuous infusion therapy , we evaluated the outcomes for 40 septic critically ill patients who received piperacillin either continuously ( 2 g intravenously ( i.v . ) over 0.5 h as a loading dose followed by 8 g i.v . daily over 24 h ( n=20 ) ) or as an intermittent infusion ( 3 g i.v . every 6h over 0.5 h ( n=20 ) ) . Results from our study demonstrated that the clinical efficacy of piperacillin as a continuous infusion is superior to intermittent administration in critically ill patients . Change in APACHE II scores from baseline at the end of the second , third and fourth days , respectively , were 4.1 , 5.1 and 5.2 for continuous infusion and 2.0 , 2.6 and 2.8 for intermittent infusion ( P < or = 0.04 ) . Considering minimum inhibitory concentrations ( MICs ) of 16 microg/mL and 32 microg/mL , the percentage of time for which piperacillin plasma concentrations were higher than the MIC ( % T > MIC ) was calculated for each patient in the two groups . For MICs of 16 microg/mL and 32 microg/mL , % T > MIC in the continuous infusion group was 100 % and 65 % of the dosing interval , respectively ; in the intermittent infusion group , % T > MIC was only 62 % and 39 % of the dosing interval . There was a significant relationship between clinical results and laboratory data . It was shown that the superiority of the clinical efficacy of continuous infusion could be related to piperacillin pharmacodynamics . Continuous infusion significantly reduced the severity of illness as demonstrated by APACHE II scores during therapy BACKGROUND Beta-lactam antibiotics are reported to exhibit time-dependent bactericidal activity . However , there are limited data on the clinical efficacy of ceftazidime administered by continuous infusion . OBJECTIVE The objective of this study was to compare the clinical efficacy of ceftazidime administered by continuous infusion and by intermittent infusion in the treatment of ventilator-associated pneumonia ( VAP ) caused by gram-negative bacteria . METHODS This was a retrospective chart review of patients with VAP caused by gram-negative bacteria who were treated with initial empiric ceftazidime therapy in the intensive care unit ( ICU ) over a 5-year period ( from June 2002 to June 2007 ) . The intermittent-infusion group received ceftazidime 2 g infused over 30 minutes every 12 hours ; the continuous-infusion group received a ceftazidime loading dose of 1 g over 30 minutes , followed by 2 g infused over 720 minutes every 12 hours . Data extracted from patients ' charts included sex , age , severity of the patient 's condition at ICU admission ( Acute Physiology and Chronic Health Evaluation II [ APACHE II ] score ) , diagnosis group , weight , creatinine clearance , MIC of the organism responsible for VAP , and severity of organ dysfunction at the time VAP was suspected ( Sepsis-related Organ Failure Assessment [ SOFA ] score ) . Each clinical history was review ed by a group of 6 staff intensivists who were blinded to whether the patient received ceftazidime by continuous or intermittent infusion . The clinical effect of treatment was categorized as cure ( complete resolution of all clinical signs and symptoms of pneumonia ) or failure ( persistence or progression of any sign or symptom of pneumonia ) . RESULTS The final sample consisted of 121 patients , of whom 88 ( 72.7 % ) were males . The mean ( SD ) age of the population was 62.87 ( 9.35 ) years . The mean APACHE II score on admission to the ICU was 16.08 ( 2.17 ) , the SOFA score at suspicion of VAP was 8.80 ( 2.06 ) , and the MIC of the organism responsible for VAP was 2.77 ( 2.24 ) microg/mL. There were no significant differences in these and other characteristics at baseline between those who received ceftazidime by continuous infusion ( n = 56 ) and those who received ceftazidime by intermittent infusion ( n = 65 ) . On logistic regression analysis , continuous infusion was associated with a greater clinical cure rate than intermittent infusion ( 50/56 [ 89.3 % ] vs 34/65 [ 52.3 % ] , respectively ; odds ratio [ OR ] = 12.2 ; 95 % CI , 3.47 - 43.21 ; P < 0.001 ) . Patients with VAP caused by organisms with an MIC of 8 microg/mL had lower cure rates compared with those with VAP caused by organisms with an MIC < or = 2 microg/mL ( OR = 0.2 ; 95 % CI , 0.04 - 0.71 ; P = 0.02 ) but not compared with those with an MIC of 4 microg/mL. No significant interaction was found between the type of ceftazidime infusion and the MIC of the causative organism . CONCLUSION In this small , selected population of adult patients with VAP caused by gram-negative bacteria who were treated in a nonr and omized , open-label manner , ceftazidime administered by continuous infusion had greater clinical efficacy than ceftazidime administered by intermittent infusion Background : It is known that β-lactam antibiotics exhibit time-dependent bactericidal activity . Several studies have found continuous infusion of meropenem more effective than intermittent infusion in maintaining constant serum concentrations in excess of the minimum inhibitory concentration . However , limited data exist on the clinical efficacy of meropenem administered by continuous infusion . Objective : To evaluate the clinical efficacy of continuous versus intermittent infusion of meropenem for the treatment of ventilator-associated pneumonia ( VAP ) due to gram-negative bacilli . Methods : A retrospective cohort study was conducted of patients with VAP caused by gram-negative bacilli who received initial empiric antibiotic therapy with meropenem . We analyzed 2 contemporary cohorts : one group received meropenem by continuous infusion ( 1 g over 360 min every 6 h ) , the other by intermittent infusion ( 1 g over 30 min every 6 h ) . The administration method was prescribed according to the physician 's discretion . Patients received meropenem plus tobramycin for 14 days . Results : There were no significant differences between patient groups with regard to gender , age , APACHE-II at intensive care unit admission , diagnosis , microorganism responsible for VAP , or organ dysfunction severity at the time VAP was suspected . The group receiving medication by continuous infusion showed a greater clinical cure rate than the group treated with intermittent infusion ( 38 of 42 , 90.47 % , vs 28 of 47 , 59.57 % , respectively , with OR 6.44 [ 95 % Cl 1.97 to 21.05 ; p < 0.001 ] ) . Conclusions : Meropenem administered by continuous infusion may have more clinical efficacy than intermittent infusion The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection . The prospect i ve r and omized parallel study was carried out in 50 patients with severe pneumonia ( n = 41 ) or bacteremia ( n = 9 ) . They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin . Patient characteristics and the minimal inhibitory concentration ( MIC ) of the isolated bacteria were comparable . Clinical outcomes were assessed along with pharmacodynamic indices and compared in both groups ( chi2 and Mann-Whitney U-tests ) . Mechanical ventilation , clinical outcome and bacteriological eradication did not significantly differ between the two groups . Also , the area under the plasma cefepime concentration curve at steady state ( AUCss : 612 + /- 369 vs. 623 + /- 319 mg x 1(-1 ) x h ) , AUCss > MIC ( 595 + /- 364 vs. 606 + /- 316 mg x 1(-1 ) x h ) and the area under the inhibitory concentration curve ( AUICss : 4258 + /- 5819 vs. 5194 + /- 7465 mg x 1(-1 ) x h ) were similar . If the time above MIC ( t > MIC ) was not significantly higher in Group 1 ( 100 + /- 0 % ) than in Group 2 ( 90 + /- 11 % ) , t > five-fold MIC in Group 1 ( 100 + /- 0 % ) was significantly higher ( p < 0.01 ) than in Group 2 ( 82 + /- 25 % ) . The mean time over the French breakpoint ( 4 mg/l ) was 100 + /- 0 % and 72 + /- 27 % in Group 1 and 2 ( p < 0.001 ) , respectively . In contrast to intermittent cefepime administration , continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens . This results in greater bactericidal activity against organisms with a higher ( 2 mg/l ) cefepime breakpoint even if the clinical outcome is not significantly modified Objective : To describe a pharmacokinetic model of piperacillin concentrations in plasma and subcutaneous tissue when administered by bolus dosing and continuous infusion in critically ill patients with sepsis on days 1 and 2 of antibiotic therapy and to compare results against previous results for piperacillin from a cohort of patients with septic shock . Design : Prospect i ve r and omized controlled trial . Setting : Eighteen-bed intensive care unit at 918-bed tertiary referral hospital . Patients : Thirteen critically ill adult patients with known or suspected sepsis in whom the treating physician deemed piperacillin – tazobactam appropriate therapy were conveniently sample d. Interventions : Patients were r and omized to receive different daily doses of piperacillin – tazobactam by bolus dosing or continuous infusion ( continuous infusion — six patients ; bolus dosing — seven patients ) . Serial plasma and tissue concentrations were determined on days 1 and 2 of treatment . Tissue concentrations of piperacillin were determined using a subcutaneously inserted microdialysis catheter . Separate pharmacokinetic models were developed for both bolus and continuous dosing . Measurements and Main Results : This is the first known article to report concurrent plasma and subcutaneous tissue concentrations of a β-lactam antibiotic administered by bolus and continuous dosing in critically ill patients with sepsis . With a 25 % lower piperacillin dose administered to the continuous infusion group , the infusion group had statistically significantly higher median plasma concentrations than the bolus group on day 2 ( 16.6 vs. 4.9 mg/L ; p = 0.007 ) . There was a trend to higher median plasma concentrations on day 1 in the bolus dosing group ( 8.9 vs. 4.9 mg/L ; p = 0.078 ) . Median tissue concentrations were not statistically different on day 1 ( infusion group 2.4 mg/L vs. bolus group 2.2 mg/L ; p = 0.48 ) and day 2 ( infusion group 5.2 mg/L vs. bolus group 0.8 mg/L ; p = 0.45 ) . A two-compartment pharmacokinetic model was found to describe the data best . Tissue pharmacodynamic targets were achieved more successfully with infusion dosing . Conclusions : Patients with sepsis do not seem to have the same level of impairment of tissue distribution as described for patients with septic shock . A 25 % lower dose of piperacillin administered by continuous infusion seems to maintain higher trough concentrations compared with st and ard bolus dosing . It is likely that the clinical advantages of continuous infusion are most likely to be evident when treating pathogens with high minimum inhibitory concentration , although without therapeutic drug monitoring and subsequent dose adjustment , infusions may never achieve target concentrations of organisms with very high minimum inhibitory concentrations in a small number of patients STUDY OBJECTIVE To determine if continuous-infusion ceftazidime is more cost-effective and efficacious than intermittent infusion in patients with nosocomial pneumonia . DESIGN Prospect i ve , open-label , r and omized trial . SETTING Large , community teaching hospital . PATIENTS Intensive care unit ( ICU ) patients with nosocomial pneumonia . INTERVENTIONS Ceftazidime 3 g/day was administered as a continuous infusion or as 2 g 3 times/day by intermittent infusion to treat nosocomial pneumonia in the ICU . Patients also received tobramycin 7 mg/kg once/day . MEASUREMENTS AND MAIN RESULTS Thirty-five patients were evaluable ; 17 received continuous infusion and 18 intermittent infusion . Clinical efficacy ( 94 % and 83 % successful outcomes with continuous and intermittent infusion , respectively ) , adverse events , and length of stay did not vary significantly between groups . Costs associated with continuous infusion , $ 627 + /- 388 , were significantly lower ( p < or = 0.001 ) than with intermittent infusion , $ 1007 + /- 430 . CONCLUSIONS Continuous infusion of ceftazidime is a cost-effective alternative to intermittent infusion for nosocomial pneumonia in the ICU ABSTRACT Ceftazidime is a beta-lactam compound that exerts a time-dependent bactericidal effect . Numerous arguments are in favor of continuous administration of ceftazidime , both for reasons of clinical efficacy and to preserve bacteriological mutation . We report a prospect i ve , single-center , parallel-group , r and omized , controlled trial comparing two modes of administration of ceftazidime , namely , continuous administration ( loading dose of 20 mg/kg of body weight followed by 60 mg/kg/day ) versus intermittent administration ( 20 mg/kg over 30 min every 8 h ) in 34 patients with ventilator-associated pneumonia due to Gram-negative bacilli . The study was performed over 48 h with 13 and 18 assessment s of serum ceftazidime in the continuous-infusion group ( group A ) and the intermittent-fusion group ( group B ) , respectively . Bronchoalveolar lavage ( BAL ) was performed at steady state in both groups at 44 h to determine ceftazidime levels in the epithelial lining fluid . We chose a predefined threshold of 20 mg/liter for serum concentrations of ceftazidime because of ecological conditions in our center . The median time above 20 mg/liter ( T>20 mg ) was 100 % in group A versus 46 % in group B. In group A , 14/17 patients had 100 % T>20 mg , versus only 1/17 patients in group B. In the epithelial lining fluid , the median concentration of ceftazidime was 12 mg/liter in group A versus 6 mg/liter in group B. A threshold of 8 mg/liter in the epithelial lining fluid was achieved twice as often in group A as in group B. This study of ceftazidime concentrations in the epithelial lining fluid indicates that continuous infusion presents advantages in terms of pharmacodynamics and predictable efficacy in patients presenting ventilator-associated pneumonia Purpose This study aims to determine if continuous infusion ( CI ) is associated with better clinical and pharmacokinetic/pharmacodynamic ( PK/PD ) outcomes compared to intermittent bolus ( IB ) dosing in critically ill patients with severe sepsis . Methods This was a two-centre r and omised controlled trial of CI versus IB dosing of beta-lactam antibiotics , which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy ( RRT ) . The primary outcome was clinical cure at 14 days after antibiotic cessation . Secondary outcomes were PK/PD target attainment , ICU-free days and ventilator-free days at day 28 post-r and omisation , 14- and 30-day survival , and time to white cell count normalisation . Results A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing . CI participants had higher clinical cure rates ( 56 versus 34 % , p = 0.011 ) and higher median ventilator-free days ( 22 versus 14 days , p < 0.043 ) than IB participants . PK/PD target attainment rates were higher in the CI arm at 100 % fT > MIC than the IB arm on day 1 ( 97 versus 70 % , p < 0.001 ) and day 3 ( 97 versus 68 % , p < 0.001 ) post-r and omisation . There was no difference in 14-day or 30-day survival between the treatment arms . Conclusions In critically ill patients with severe sepsis not receiving RRT , CI demonstrated higher clinical cure rates and had better PK/PD target attainment compared to IB dosing of beta-lactam antibiotics . Continuous beta-lactam infusion may be mostly advantageous for critically ill patients with high levels of illness severity and not receiving RRT . Malaysian National Medical Research Register ID : NMRR-12 - 1013 - 14017 RATIONALE Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing . OBJECTIVES To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis . METHODS We conducted a r and omized controlled trial in 25 intensive care units ( ICUs ) . Participants commenced on piperacillin-tazobactam , ticarcillin-clavulanate , or meropenem were r and omized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge . The primary outcome was the number of alive ICU-free days at Day 28 . Secondary outcomes were 90-day survival , clinical cure 14 days post antibiotic cessation , alive organ failure-free days at Day 14 , and duration of bacteremia . MEASUREMENTS AND MAIN RESULTS We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20 . There was no difference in ICU-free days : 18 days ( interquartile range , 2 - 24 ) and 20 days ( interquartile range , 3 - 24 ) in the continuous and intermittent groups ( P = 0.38 ) . There was no difference in 90-day survival : 74.3 % ( 156 of 210 ) and 72.5 % ( 158 of 218 ) ; hazard ratio , 0.91 ( 95 % confidence interval , 0.63 - 1.31 ; P = 0.61 ) . Clinical cure was 52.4 % ( 111 of 212 ) and 49.5 % ( 109 of 220 ) ; odds ratio , 1.12 ( 95 % confidence interval , 0.77 - 1.63 ; P = 0.56 ) . There was no difference in organ failure-free days ( 6 d ; P = 0.27 ) and duration of bacteremia ( 0 d ; P = 0.24 ) . CONCLUSIONS In critically ill patients with severe sepsis , there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion . Australian New Zeal and Clinical Trials Registry number ( ACT RN12612000138886 ) OBJECTIVES To compare the clinical and bacteriological outcome of critically ill patients with sepsis treated by ceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion . PATIENTS AND METHODS We conducted an open-label , r and omized controlled pilot study in 57 patients clinical ly diagnosed with sepsis ( suspected/proven infection and systemic inflammatory response syndrome ) in a tertiary level intensive care unit . Patients were r and omized to receive 2 g of ceftriaxone administered by once-daily intermittent bolus dosing or by 24 h continuous infusion . Clinical and bacteriological outcomes were assessed by blinded clinicians . RESULTS Fifty-seven patients were enrolled in the study , 50 of whom fulfilled the a priori definition of treatment for 4 or more days . The infusion ( n = 29 ) and bolus groups ( n = 28 ) were similar in terms of demographics , although the median age of those receiving the infusion was younger . Intention-to-treat analysis found no statistically significant differences in the primary outcomes for clinical response ( P = 0.17 ) , clinical cure [ infusion n = 13/29 versus bolus n = 5/28 ; adjusted odds ratio ( AOR ) = 3.74 ; 95 % confidence interval ( 95 % CI ) = 1.11 - 12.57 ; P = 0.06 ] , bacteriological response ( P = 0.41 ) and bacteriological cure ( infusion n = 18/29 versus bolus 14/28 ; AOR = 1.64 ; 95 % CI = 0.57 - 4.70 ; P = 0.52 ) . However , logistic regression in patients that complied with the a priori definitions who received ceftriaxone by continuous infusion ( AOR = 22.8 ; 95 % CI = 2.24 - 232.3 ; P = 0.008 ) or patients with a low Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ( AOR = 0.70 ; 95 % CI = 0.54 - 0.91 ; P = 0.008 ) were associated with an improved clinical outcome when age and Sepsis Organ Failure Assessment ( SOFA ) score at time of study entry were controlled for . CONCLUSIONS This pilot study suggests clinical and bacteriological advantages of continuous infusion of ceftriaxone over bolus administration in critically ill patients in patients requiring 4 or more days of treatment . This sets the scene for a large multicentre double-blind r and omized controlled trial to confirm these findings BACKGROUND The adequacy of intermittent and continuous infusion ceftazidime for the treatment of nosocomial pneumonia in critically ill trauma patients was assessed by analyzing ceftazidime pharmacokinetics in relation to the minimum inhibitory concentration ( MIC ) and treatment outcome . METHODS Serial blood sample s were obtained during ceftazidime therapy in 31 trauma patients . Ceftazidime pharmacokinetics were compared with that of previously studied healthy volunteers . Ceftazidime pharmacokinetics were analyzed according to the time above the MIC and treatment outcome . RESULTS Critically ill trauma patients had a significantly increased volume of distribution and clearance ( 0.32 + /- 0.14 L/kg and 2.35 + /- 0.89 mL. min(-1 ) . kg(-1 ) , respectively ) compared with healthy volunteers ( 0.21 + /- 0.03 and 1.58 + /- 0.23 mL. min(-1 ) . kg(-1 ) ) . The time above the MIC was > /=92 % of the dosing interval for all patients and treatment outcomes were similar between the two treatment groups . CONCLUSIONS Ceftazidime pharmacokinetics are significantly altered in critically ill trauma patients . Both intermittent and continuous ceftazidime regimens were equally effective for the treatment of nosocomial pneumonia caused by less virulent bacteria CONTEXT Infection is a major cause of morbidity and mortality in intensive care units ( ICUs ) worldwide . However , relatively little information is available about the global epidemiology of such infections . OBJECTIVE To provide an up-to- date , international picture of the extent and patterns of infection in ICUs . DESIGN , SETTING , AND PATIENTS The Extended Prevalence of Infection in Intensive Care ( EPIC II ) study , a 1-day , prospect i ve , point prevalence study with follow-up conducted on May 8 , 2007 . Demographic , physiological , bacteriological , therapeutic , and outcome data were collected for 14,414 patients in 1265 participating ICUs from 75 countries on the study day . Analyses focused on the data from the 13,796 adult ( > 18 years ) patients . RESULTS On the day of the study , 7087 of 13,796 patients ( 51 % ) were considered infected ; 9084 ( 71 % ) were receiving antibiotics . The infection was of respiratory origin in 4503 ( 64 % ) , and microbiological culture results were positive in 4947 ( 70 % ) of the infected patients ; 62 % of the positive isolates were gram-negative organisms , 47 % were gram-positive , and 19 % were fungi . Patients who had longer ICU stays prior to the study day had higher rates of infection , especially infections due to resistant staphylococci , Acinetobacter , Pseudomonas species , and C and ida species . The ICU mortality rate of infected patients was more than twice that of noninfected patients ( 25 % [ 1688/6659 ] vs 11 % [ 682/6352 ] , respectively ; P < .001 ) , as was the hospital mortality rate ( 33 % [ 2201/6659 ] vs 15 % [ 942/6352 ] , respectively ; P < .001 ) ( adjusted odds ratio for risk of hospital mortality , 1.51 ; 95 % confidence interval , 1.36 - 1.68 ; P < .001 ) . CONCLUSIONS Infections are common in patients in contemporary ICUs , and risk of infection increases with duration of ICU stay . In this large cohort , infection was independently associated with an increased risk of hospital death This prospect i ve pharmacokinetic study aim ed to compare the clearance of piperacillin-tazobactam administered as a 24-h continuous infusion between continuous venovenous haemodiafiltration ( CVVHDF ) and continuous venovenous haemofiltration ( CVVH ) applied at equal dose in critically ill patients . A loading dose of 4.5 g of piperacillin-tazobactam followed by a continuous infusion ( 500 mg/h ) was administered to patients r and omized to receive CVVHDF or CVVH . Serial pre- and postfilter blood sample s were drawn during an 8-h sampling interval . Piperacillin plasma concentrations were measured using a vali date d chromatography method . Piperacillin pharmacokinetics were calculated using a non-compartmental approach . In total , 212 piperacillin plasma concentrations were determined . Median [ interquartile range ( IQR ) ] total piperacillin clearance was 7.5 ( 5.9 - 11.2 ) L/h in the CVVHDF group and 4.7 ( 4.5 - 9.6 ) L/h in the CVVH group ( P = 0.21 ) . Median ( IQR ) piperacillin clearance related to continuous renal replacement therapy ( CRRT ) was 3.0 ( 2.7 - 3.2 ) L/h in the CVVHDF group and 2.6 ( 1.9 - 3.0 ) L/h in the CVVH group ( P = 0.29 ) . Mean ( st and ard deviation ) steady state concentrations were 68.4 ( 25.8 ) mg/L in the CVVHDF group and 89.1 ( 35.6 ) mg/L in the CVVH group ( P = 0.16 ) . The estimated unbound concentrations result ing from piperacillin continuous infusion were above the target susceptibility breakpoint ( 16 mg/L ) for the entire dosing interval ( 100 % fT > MIC ) in all study patients . In the present study , higher ( but not significantly ) piperacillin clearance and lower piperacillin exposure were observed in patients receiving CVVHDF compared with CVVH . In patients receiving CRRT , the use of piperacillin continuous infusion should be considered to ensure optimal exposure for less susceptible pathogens |
2,128 | 25,634,166 | The items were stratified as follows : Pilates method versus other kind of exercises ( n = 6 trials ) and Pilates method versus no treatment group or minimal intervention for short-term pain ( n = 9 trials ) ; the therapeutic effect of the Pilates method in r and omized cohorts ( n = 5 ) ; and analysis of review s ( n = 9).We found that there is a dearth of studies that clearly demonstrates the efficacy of a specific Pilates exercise program over another in the treatment of chronic pain .
However , the consensus in the field suggests that Pilates method is more effective than minimal physical exercise intervention in reducing pain . | Abstract The Pilates method has recently become a fast-growing popular way of exercise recommended for healthy individuals and those engaged in rehabilitation .
Several published studies have examined the effects of Pilates method in people with chronic low back pain (LBP).The objective of this study is to describe and provide an extensive overview of the scientific literature comparing the effectiveness of the Pilates method on pain and disability in patients with chronic nonspecific LBP . | Objectives : To present the prevalence of self reported musculoskeletal diseases , the coexistence of these diseases , the test-retest reliability with six months in between , and the association with musculoskeletal pain symptoms . Methods : Twelve layman descriptions of common musculoskeletal diseases were part of the question naires of a prospect i ve cohort study of a r and om sample in the general Dutch population aged 25 years or more ( baseline : n=3664 , follow up after six months : n=2338 ) . Data collection also included information about pain relating to five different anatomical areas . Results : Osteoarthritis of the knee ( men 10.1 % , women 13.6 % ) was amongst the most reported musculoskeletal diseases , whereas the figures for self reported rheumatoid arthritis ( RA ) were 1.6 % and 4.6 % for men and women , respectively . The coexistence of these diseases is high : 47 of the 66 combinations were reported more often than would be expected if they were independent of each other ( p<0.05 ) . For most diseases the test-retest reliability was good ( κ between 0.6 and 0.8 ) , but for repetitive strain injury ( κ=0.37 ) and chronic arthritis other than RA ( κ=0.44 ) the agreement was fair to moderate . All complaints of pain were more often reported by those with musculoskeletal diseases than those without those diseases , and the pain pattern was disease-specific . Conclusions : Self reported musculoskeletal diseases are highly prevalent , with a fair to good reliability and a disease-specific pain pattern . Health surveys are a limited but valuable source of information for this group of health problems , which is not available from most other sources of information OBJECTIVE The present study aim ed to evaluate the effects of Pilates exercise program on pain , functional status and quality of life in women with postmenopausal osteoporosis . DESIGN The study was performed as a r and omized , prospect i ve , controlled and single-blind trial . PARTICIPATIONS : Seventy women ( age range , 45 - 65 years ) with the diagnosis of postmenopausal osteoporosis were included . METHODS AND INTERVENTIONS Patients were r and omly allocated into two groups ( home and Pilates exercise groups ) . Patients in the Pilates exercise group underwent a supervised Pilates exercise program twice a week for one year . Patients in the home exercise group were asked to perform a home exercise program consisting of thoracic extension exercises . Patients were evaluated at baseline and after one year of participation in the exercise programs . MAIN OUTCOME MEASUREMENTS Visual Analog Scale for pain , six-minute walking and sit-to-st and tests for functional status , and the Qualeffo-41 Question naire and the Short Form-36 ( SF-36 ) for quality of life . Patients were also asked to report the number of falls during the intervention . RESULTS At the end of the study , the results of 60 patients were analyzed . A significant improvement was noted in all evaluation parameters at the end of the exercise program in the Pilates exercise group . Except for Qualeffo- Leisure Time Activities , SF-36 physical role limitation and emotional role limitation subscales , a significant improvement was noted in all other evaluation parameters at the end of the exercise program in the home exercise group . Improvement was significantly greater in the Pilates exercise group compared to the home exercise group in all parameters . CONCLUSION Pilates exercises may be a safe and an effective treatment alternative for the quality of life in patients with postmenopausal osteoporosis Background Chronic low back pain is an expensive and difficult condition to treat . One of the interventions widely used by physiotherapists in the treatment of chronic non-specific low back pain is exercise therapy based upon the Pilates principles . Pilates exercises can be performed with or without specific equipment . These two types of Pilates exercises have never been compared on a high- quality r and omised controlled trial . Methods / design This r and omised controlled trial with a blinded assessor will evaluate eighty six patients of both genders with chronic low back pain , aged between 18 and 60 years , from one Brazilian private physiotherapy clinic . The patients will be r and omly allocated into two groups : Mat Group will perform the exercises on the ground while the Equipment-based Group will perform the Pilates method exercises on the following equipment : Cadillac , Reformer , Ladder Barrel , and Step Chair . The general and specific disability of the patient , kinesiophobia , pain intensity and global perceived effect will be evaluated by a blinded assessor before r and omisation and at six weeks and six months after r and omisation . In addition , the expectation of the participants and their confidence with the treatment will be evaluated before r and omisation and after the first treatment session , respectively . Discussion This will be the first study aim ing to compare the effectiveness of Mat and Equipment-based Pilates exercises in patients with chronic non-specific low back pain . The results may help health-care professionals in clinical decision-making and could potentially reduce the treatment costs of this condition . Trial registration Brazilian Registry of Clinical Trials UNLABELLED Altan L , Korkmaz N , Bingol U , Gunay B. Effect of Pilates training on people with fibromyalgia syndrome : a pilot study . OBJECTIVE To investigate the effects of Pilates on pain , functional status , and quality of life in fibromyalgia , which is known to be a chronic musculoskeletal disorder . DESIGN R and omized , prospect i ve , controlled , and single-blind trial . SETTING Physical medicine and rehabilitation department . PARTICIPANTS Women ( N=50 ) who had a diagnosis of fibromyalgia syndrome ( FMS ) according to the American College of Rheumatology criteria . INTERVENTION The participants were r and omly assigned into 2 groups . In group 1 , a Pilates exercise program of 1 hour was given by a certified trainer to 25 participants 3 times a week for 12 weeks . In group 2 , which was design ed as the control group , 25 participants were given a home exercise ( relaxation/stretching ) program . In both groups , pre- ( week 0 ) and posttreatment ( week 12 and week 24 ) evaluation was performed by one of the authors , who was blind to the group allocation . MAIN OUTCOME MEASURES Primary outcome measures were pain ( visual analog scale ) and Fibromyalgia Impact Question naire ( FIQ ) . Exploratory outcome measures were number of tender points , algometric score , chair test , and Nottingham Health Profile . RESULTS Twenty-five Pilates exercise and 24 relaxation/stretching exercise participants completed the study . In group 1 , significant improvement was observed in both pain and FIQ at week 12 but only in FIQ at 24 weeks . In group 2 , no significant improvement was obtained in pain and FIQ at week 12 and week 24 . Comparison of the 2 groups showed significantly superior improvement in pain and FIQ in group 1 at week 12 but no difference between the 2 groups at week 24 . CONCLUSIONS We suggest Pilates as an effective and safe method for people with FMS . Our study is the first clinical study design ed to investigate the role of the Pilates method in FMS treatment . We believe that further research with more participants and longer follow-up periods could help assess the therapeutic value of this popular physical exercise method [ Purpose ] The purpose of this study was to examine the influence of mat Pilates and apparatus Pilates on pain and static balance of businesswomen with chronic back pain . [ Subjects and Methods ] Participants were r and omly allocated to Pilates mat exercises ( PME ) or Pilates apparatus exercise ( PAE ) , and performed the appropriate Pilates exercises 3 days per week for 8 weeks . In order to measure the improvement in the participants ’ static balance ability as a result of the exercise , the sway length and sway velocity of the subjects were measured before and after the experiment while the subjects stood on a Balance Performance Monitor ( BPM ) facing the front wall for 30 seconds with their eyes open . The visual analogue scale ( VAS ) was used to measure the degree of pain . [ Results ] The VAS score , sway length , and sway velocity of both groups decreased significantly after the experiment , but the PME group showed a greater decrease than the PAE group . [ Conclusion ] PME showed greater improvement in pain level and balance compared with PAE in this research . Since the subjects of this study were patients with low back pain , PME is assumed to have been more suitable and effective because it uses body weight to strengthen core muscles rather than heavier apparatuses as in PAE PURPOSE This single-assessor-blinded r and omized controlled trial aim ed to compare the efficacy of physiotherapy-delivered clinical Pilates and general exercise for chronic low back pain . METHODS Eighty-seven community volunteers with low back pain for ≥3 months and age 18 - 70 were r and omized to either the Pilates ( n = 44 ) or general exercise ( n = 43 ) group . The primary outcome was pain/disability measured with the Quebec scale . Secondary outcomes included pain on a numeric rating scale , Patient-Specific Functional Scale , Pain Self-efficacy Question naire , quality of life , and global perceived effect of treatment . All participants attended 60-min exercise sessions twice weekly for 6 wk supervised by a physiotherapist and performed daily home exercises that were continued during the follow-up . Participants from the clinical Pilates group received an individualized direction-specific exercise program prescribed by the physiotherapist after a clinical examination . The general exercise group received a generic set of exercises that were multidirectional and nonspecific . Outcomes were assessed after 6 wk ( primary time point ) and at 12 and 24 wk . Differences in mean change were compared between groups using ANCOVA adjusted for baseline values of the outcome . RESULTS Eighty-three participants ( 96 % ) completed the 6-wk intervention and 60 ( 69 % ) completed the 24-wk follow-up . At 6 wk , no difference was found between groups for change in the Quebec scale ( 3.5 , 95 % confidence interval = -7.3 to 0.3 , P = 0.07 ) ; both groups showed significant improvements . Similar results were found at the 12- and 24-wk follow-up and for the secondary outcome measures . CONCLUSIONS An individualized clinical Pilates program produced similar beneficial effects on self-reported disability , pain , function and health-related quality of life as a general exercise program in community volunteers with chronic low back pain Study Design . R and omized controlled trial . Objective . This is the companion study to a previous publication that presented 8-week pain , disability , and trunk muscle motor control results . The objective of this study was to compare the effect of 8 weeks of specific trunk exercises and stationary cycling on outcomes measures of catastrophizing and fear-avoidance beliefs ( FAB ) in patients with chronic nonspecific low back pain , and provide 6-month outcome data for all self-report measures . Summary of Background Data . It is thought that any form of moderate-to-vigorous physical activity is sufficient to address catastrophizing and FAB , and concomitant levels of pain and disability . Methods . Sixty-four patients with low back pain were r and omly assigned to 8 weeks of specific trunk exercise group ( SEG ) , or stationary cycling group ( CEG ) . Self-rated pain , disability , catastrophizing and FAB scores were collected before , immediately after ( 8 wk ) , and 6 months after the training program . Clinical ly meaningful improvements were defined as greater than a 30 % reduction from baseline in pain and disability scores . “ Intention-to-treat ” principles were used for missing data . Per- protocol analysis was performed on participants who attended at least two-thirds of the exercise sessions . Results . At 8 weeks , disability was significantly lower in the SEG compared with the CEG ( d = 0.62 , P = 0.018 ) . Pain was reduced from baseline in both the groups after training ( P < 0.05 ) , but was lower for the SEG ( P < 0.05 ) . FAB scores were reduced in the SEG at 8 weeks , and in the CEG at 6 months . No between-group differences in FAB scores were observed . Similar reductions in catastrophizing in each group were observed at each time point . At 6 months , the overall data pattern suggested no long-term difference between groups . Per- protocol analysis of clinical ly meaningful improvements suggests no between-group differences for how many patients are likely to report improvement . Conclusion . Inferential statistics suggest greater improvements at 8 weeks , but not 6 months , for the SEG . Inspection of clinical ly meaningful changes based on a minimum level of adherence suggests no between-group differences . If a patient with low back pain adheres to either specific trunk exercises or stationary cycling , it is reasonable to think that similar improvements will be achieved . Level of Evidence : OBJECTIVE To evaluate the influence of pain on vertical ground-reaction force ( VGRF ) in patients with low back problems and the effect of the Pilates method on the gait of these patients . DESIGN A single-blind r and omized controlled trial . PARTICIPANTS 28 individuals assigned to a control group ( n = 11 ) and a low-back group ( n = 17 ) , the latter of which was subdivided into a Pilates group ( n = 8) and a no-Pilates group ( n = 9 ) . INTERVENTION The Pilates group undertook 15 sessions of Pilates . MAIN OUTCOME MEASURES The VGRF parameters were recorded during preferred and faster walking speeds . The data were collected before and after the intervention . RESULTS The weight-acceptance rate and push-off rate were significantly less in the right lower limb of low-back group than of the control group at preferred speed . Improvements were seen in the Pilates group postintervention , with increased middle-support force for the left lower limb at faster walking speed and decreased pain ; this did not occur in the no-Pilates group . CONCLUSIONS These results suggest that patients with low back pain use strategies to attenuate the amount of force imposed on their body . The Pilates method can improve weight discharge in gait and reduce pain compared with no intervention BACKGROUND Low back pain is highly prevalent in patients with HTLV-1 . The effects of physical activity on this condition are not known , but postural misalignment and motor deficits are frequently present . OBJECTIVES To assess the effect of Pilates exercises on chronic low back pain in these patients , and its impact on quality of life . METHODS A r and omized crossover clinical trial was conducted , involving 22 patients from a reference center in Salvador , Bahia , Brazil . The VAS was used to evaluate the effect of Pilates on pain intensity and the SF-36 to assess its impact on quality of life . RESULTS Our results provide evidence of positive effects on pain intensity and almost all domains of quality of life when patients followed the Pilates exercise program described . CONCLUSION The Pilates method may be a useful tool in alleviating the symptoms of low back pain , and had a significant impact on quality of life in this sample of patients OBJECTIVES Verbally administered numerical rating scales ( NRSs ) from 0 to 10 are often used to measure pain , but they have not been vali date d in the emergency department ( ED ) setting . The authors wished to assess the comparability of the NRS and visual analog scale ( VAS ) as measures of acute pain , and to identify the minimum clinical ly significant difference in pain that could be detected on the NRS . METHODS This was a prospect i ve cohort study of a convenience sample of adults presenting with acute pain to an urban ED . Patients verbally rated pain intensity as an integer from 0 to 10 ( 0 = no pain , 10 = worst possible pain ) , and marked a 10-cm horizontal VAS bounded by these descriptors . VAS and NRS data were obtained at presentation , 30 minutes later , and 60 minutes later . At 30 and 60 minutes , patients were asked whether their pain was " much less , " " a little less , " " about the same , " " a little more , " or " much more . " Differences between consecutive pairs of measurements on the VAS and NRS obtained at 30-minute intervals were calculated for each of the five categories of pain descriptor . The association between VAS and NRS scores was expressed as a correlation coefficient . The VAS scores were regressed on the NRS scores in order to assess the equivalence of the measures . The mean changes associated with descriptors " a little less " or " a little more " were combined to define the minimum clinical ly significant difference in pain measured on the VAS and NRS . RESULTS Of 108 patients entered , 103 provided data at 30 minutes and 86 at 60 minutes . NRS scores were strongly correlated to VAS scores at all time periods ( r = 0.94 , 95 % CI = 0.93 to 0.95 ) . The slope of the regression line was 1.01 ( 95 % CI = 0.97 to 1.06 ) and the y-intercept was -0.34 ( 95 % CI = -0.67 to -0.01 ) . The minimum clinical ly significant difference in pain was 1.3 ( 95 % CI = 1.0 to 1.5 ) on the NRS and 1.4 ( 95 % CI = 1.1 to 1.7 ) on the VAS . CONCLUSIONS The findings suggest that the verbally administered NRS can be substituted for the VAS in acute pain measurement STUDY DESIGN A r and omized controlled trial , prestest-posttest design , with a 3- , 6- , and 12-month follow-up . OBJECTIVES To investigate the efficacy of a therapeutic exercise approach in a population with chronic low back pain ( LBP ) . BACKGROUND Therapeutic approaches developed from the Pilates method are becoming increasingly popular ; however , there have been no reports on their efficacy . METHODS AND MEASURES Thirty-nine physically active subjects between 20 and 55 years old with chronic LBP were r and omly assigned to 1 of 2 groups . The specific-exercise-training group participated in a 4-week program consisting of training on specialized ( Pilates ) exercise equipment , while the control group received the usual care , defined as consultation with a physician and other specialists and healthcare professionals , as necessary . Treatment sessions were design ed to train the activation of specific muscles thought to stabilize the lumbar-pelvic region . Functional disability outcomes were measured with The Rol and Morris Disability Question naire ( RMQ/RMDQ-HK ) and average pain intensity using a 101-point numerical rating scale . RESULTS There was a significantly lower level of functional disability ( P = .023 ) and average pain intensity ( P = .002 ) in the specific-exercise-training group than in the control group following the treatment intervention period . The posttest adjusted mean in functional disability level in the specific-exercise-training group was 2.0 ( 95 % CI , 1.3 to 2.7 ) RMQ/RMDQ-HK points compared to a posttest adjusted mean in the control group of 3.2 ( 95 % CI , 2.5 to 4.0 ) RMQ/RMDQ-HK points . The posttest adjusted mean in pain intensity in the specific-exercise-training group was 18.3 ( 95 % CI , 11.8 to 24.8 ) , as compared to 33.9 ( 95 % CI , 26.9 to 41.0 ) in the control group . Improved disability scores in the specific-exercise-training group were maintained for up to 12 months following treatment intervention . CONCLUSIONS The individuals in the specific-exercise-training group reported a significant decrease in LBP and disability , which was maintained over a 12-month follow-up period . Treatment with a modified Pilates-based approach was more efficacious than usual care in a population with chronic , unresolved LBP OBJECTIVES To describe the impact of musculoskeletal pain ( MP ) ; to compare management of MP by the population and by primary care physicians ; and to identify misconceptions about treatment . METHODS 5803 people with MP and 1483 primary care physicians , r and omly selected , in eight European countries were interviewed by telephone . A structured question naire was used to ask about usual management of MP and perceived benefits and risks of treatment . Current health status ( SF-12 ) was also assessed . RESULTS From primary care physicians ' perceptions , MP appears to be well managed . All presenting patients are offered some form of treatment , 90 % or more doctors are trying to improve patients ' quality of life , and most are aware and concerned about the risks of treatment with NSAIDs . From a population perspective , up to 27 % of people with pain do not seek medical help and of those who do , several wait months/years before seeing a doctor . 55 % or fewer patients who have seen a doctor are currently receiving prescription treatment for their pain . Communication between doctors and patients is poor ; few patients are given information about their condition ; and many have misconceptions about treatment . CONCLUSIONS Management of MP is similar across eight European countries , but there is discordance between physician and patient perspectives of care . Some people with pain have never sought medical help despite being in constant/daily pain . Those who do seek help receive little written information or explanation and many have misperceptions about the benefits and risks of treatment that limit their ability to actively participate in decisions about their care Neck pain is becoming increasingly more common and multiple interventions have been advocated in its management . The literature supports the use of a variety of exercises including specific low load endurance exercises , scapular muscle retraining and neck and upper limb strengthening . Pilates is one form of exercise that is developing in popularity . This pilot uncontrolled study investigates whether a 6-week matwork based Pilates programme can change outcome measures in a group of chronic neck pain patients . Thirteen subjects were assessed on self-report tests ; neck disability index ( NDI ) , patient specific functional scale ( PSFS ) , numerical rating pain scale ( NRPS ) and one objective measure ; the abdominal drawing in test ( ADIT ) . A statistically significant improvement was obtained in the disability outcomes ( NDI and PSFS ) at both 6 and 12 weeks . The NRPS also demonstrated statistical improvement at 12 weeks but not at 6 . The minimal clinical ly important difference ( MCID ) is the score that reflects a change that is meaningful for the patient and this was achieved at 12-weeks for the NDI ( > 5 points ) , PSFS ( > 3 points ) and NRPS ( > 2 points ) . Only 2 subjects reached normal levels in the ADIT at 12-weeks . The results of this pilot study suggest that Pilates has a role to play in reducing pain and disability in neck pain patients The objectives of this study were to compare the effects of three different Pilates regimes on chronic , mild low back pain symptoms and to determine whether the efficiency of load transfer through the pelvis is improved by those exercises . A between subjects equivalent group experimental design was used . The independent variable was the type of exercise training ( three groups ) and the two-dependent variables were low back pain symptoms and load transfer through the pelvis . The outcome measures of the first-dependent variable were a comparison between modified Oswestry Disability Question naires ( one of the st and ard pain instruments ) completed pre- and post-program and frequency , intensity and duration of low back pain . The outcome measure of the second-dependent variable , efficiency of load transfer through the pelvis was the Stork test ( one-legged st and ing test ) in weight bearing . Although all groups experienced statistically significant reductions in frequency , intensity and duration of low back pain across the weeks of exercising , there were no significant differences between the groups relative to each other BACKGROUND Studies have shown the effectiveness of a few weekly pilates sessions as helping to reduce lower back pain ( LBP ) . However many patients fear that physical activity can actually make the pain and disability worse . DESIGN We carried out this observational prospect i ve clinical study to look at the effects that taking part in daily pilates has one on side and on the other the effects of LBP management without physical exercise . SETTING The volunteers who participated in this study were recruited from among some local cultural associations . POPULATION Patients affected by LBP were evaluated . METHODS The subjects were 60 volunteers ( 27 males and 33 females ) with a mean age of 51.2 years who had chronic low back pain ( CLBP ) . They were allocated to pilates group ( N.=30 ) or inactivity control group ( N.=30 ) . The pilates group performed one-hour lesson of pilates exercise , 5 lessons per week during the following 6 months . The inactivity group continued with their normal daily activities . The Rol and -Morris Disability , the Oswestry , the SF-36 and the Spinal Functional Sort Question aries of all subjects were measured at the baseline ( T1 ) and at 6 months ( T2 ) . RESULTS At T2 improvements were observed in the pilates group with increases in physical and social functioning , general health and vitality ( P<0.05 ) and decreases in disability and pain ( P<0.05 ) . The inactivity group showed worsening in the same measures at T2 . CONCLUSION We found an important improvement of pain , disability and physical and psychological perception of health in individuals who did the daily sessions of pilates . CLINICAL REHABILITATION IMPACT Some authors underlined the possible risk of a lack of adherence to an exercise program at home . This study suggests that a daily pilates program is effective for the management of CLBP . On the other h and , the inactivity contributes to further worsening , inducing a vicious cycle in which pain and physical activity intolerance follow each other Having a sense of control despite experiencing chronic pain has a positive effect on patients ' coping abilities . Investigating patients ' perception of the control they have over pain may be possible by using a visual analogue scale Objective : To assess the effectiveness of pilates method on patients with chronic non-specific low back pain ( LBP ) . Method : A r and omized controlled trial was carried out in sixty patients with a diagnosis of chronic non-specific LBP . Patients were r and omly assigned to one of two groups : Experimental Group ( EG ) that maintained medication treatment with use of NSAID and underwent treatment with the pilates method and Control Group ( CG ) that continue medication treatment with use of NSAID and did not undergo any other intervention . A blinded assessor performed all evaluations at baseline ( T0 ) , after 45 , 90 , and 180 days ( T45 , T90 and T180 ) for : pain ( VAS ) , function ( Rol and Morris question naire ) , quality of life ( SF-36 ) , satisfaction with treatment ( Likert scale ) , flexibility ( sit and reach test ) and NSAID intake . Results : The groups were homogeneous at baseline . Statistical differences favoring the EG were found with regard to pain ( P < 0.001 ) , function ( P < 0.001 ) and the quality of life domains of functional capacity ( P < 0.046 ) , pain ( P < 0.010 ) and vitality ( P < 0.029 ) . Statistical differences were also found between groups regarding the use of pain medication at T45 , T90 and T180 ( P < 0.010 ) , with the EG taking fewer NSAIDs than the CG . Conclusions : The pilates method can be used by patients with LBP to improve pain , function and aspects related to quality of life ( functional capacity , pain and vitality ) . Moreover , this method has no harmful effects on such patients Background The Pilates method has been used to improve function and reduce pain in patients with chronic nonspecific low back pain , although there is little scientific evidence that describes its efficacy . Objective The purpose of this study was to investigate the effectiveness of the addition of modified Pilates exercises to minimal intervention in patients with chronic low back pain . Design A r and omized controlled trial was conducted . Setting The study was done in an outpatient physical therapy department in Brazil . Patients Eighty-six patients with chronic nonspecific low back pain participated in the study . Intervention All participants received an education booklet containing information about low back pain and were r and omly allocated to receive 12 sessions , over 6 weeks , of exercises based upon Pilates principles ( n=43 ) or of education alone ( n=43 ) . Measurements Primary outcomes were pain intensity and disability measured at 6 weeks and 6 months . Secondary outcomes were patient-specific functional disability , global impression of recovery , and kinesiophobia measured at 6 weeks and 6 months . All outcomes were measured by a blinded assessor in all time points . Results There was no loss to follow-up at any of the time points . Improvements were observed in pain ( mean difference=2.2 points , 95 % confidence interval [CI]=1.1 to 3.2 ) , disability ( mean difference=2.7 points , 95 % CI=1.0 to 4.4 ) , and global impression of recovery ( mean difference=−1.5 points , 95 % CI=−2.6 to −0.4 ) in favor of the Pilates group after intervention , but these differences were no longer statistically significant at 6 months . Limitations Treatment provider and participants could not be blinded to the interventions . Conclusions The addition of modified Pilates exercises to an educational booklet provides small benefits compared with education alone in patients with chronic nonspecific low back pain ; however , these effects were not sustained over time Background The Pilates method has been widely used to treat patients with chronic low back pain . Pilates exercises can be performed in 2 ways : by using specific equipment or without it ( also known as mat Pilates ) . There are no studies , however , that have compared the effectiveness of mat Pilates with that of equipment-based Pilates . Objective The aim of this study was to compare the effectiveness of mat Pilates and equipment-based Pilates in patients with chronic nonspecific low back pain . Design A 2-arm r and omized controlled trial with a blinded assessor was conducted . Setting The study was conducted at a private physical therapy clinic in Brazil . Patients Eighty-six patients with chronic nonspecific low back pain participated . Intervention The patients were r and omly allocated to 1 of 2 groups : a mat Pilates group ( n=43 ) and an equipment-based Pilates group ( n=43 ) . The participants in both groups attended 12 Pilates sessions over a period of 6 weeks . Measurements The primary outcomes were pain intensity and disability . The secondary outcomes were global perceived effect , patient 's specific disability , and kinesiophobia . A blinded assessor evaluated the outcomes at baseline and 6 weeks and 6 months after r and omization . Results After 6 months , there was a statistically significant difference for disability ( mean difference=3.0 points , 95 % confidence interval [CI]=0.6 to 5.4 ) , specific disability ( mean difference=−1.1 points , 95 % CI=−2.0 to −0.1 ) , and kinesiophobia ( mean difference=4.9 points , 95 % CI=1.6 to 8.2 ) in favor of equipment-based Pilates . No differences were found for the remaining outcomes . Conclusions Equipment-based Pilates was superior to mat Pilates in the 6-month follow-up for the outcomes of disability and kinesiophobia . These benefits were not observed for pain intensity and global perceived effect in patients with chronic nonspecific low back pain |
2,129 | 16,796,762 | Evidence from RCTs forms the basis of meta-analyses and systematic review s. This hierarchy , founded on a pharmacological model of therapy , is generalized to other interventions which may be complex and non-pharmacological ( healing , acupuncture and surgery ) .
Discussion The hierarchical model is valid for limited questions of efficacy , for instance for regulatory purpose s and newly devised products and pharmacological preparations .
It is inadequate for the evaluation of complex interventions such as physiotherapy , surgery and complementary and alternative medicine ( CAM ) . | Background The reasoning behind evaluating medical interventions is that a hierarchy of methods exists which successively produce improved and therefore more rigorous evidence based medicine upon which to make clinical decisions . | A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were r and omly selected for one of four consultations : a consultation conducted in a " positive manner , " with and without treatment , and a consultation conducted in a " non-positive manner , " called a negative consultation , with and without treatment . Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups . Similarly , 64 % of those receiving a positive consultation got better , compared with 39 % of those who received a negative consultation ( p = 0.001 ) and 53 % of those treated got better compared with 50 % of those not treated ( p = 0.5 ) Summary The efficacy of naproxen and paracetamol in relieving uterine cramps has been compared in a sequential trial . The treatments did not differ significantly in a two-sided test in 56 patients . A corresponding fixed sample test would have required 140 patients to obtain the same significance level and power . In addition to uterine pain , the effect on episiotomy pain was also estimated at the termination of the trial . Again , there seemed to be no difference between naproxen and paracetamol BACKGROUND For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For each treatment , the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis -of-variance procedure and then compared with the combined magnitude of the effects in the r and omized , controlled trials that evaluated the same treatment . RESULTS There were 136 reports about 19 diverse treatments , such as calcium-channel-blocker therapy for coronary artery disease , appendectomy , and interventions for subfertility . In most cases , the estimates of the treatment effects from observational studies and r and omized , controlled trials were similar . In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the r and omized , controlled trials . CONCLUSIONS We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in r and omized , controlled trials Patients who agree and those who refuse clinical trial entry may differ in attitudes towards decision control and the benefits associated with the trial arms . These differences , if they exist , have implication s for the process of obtaining informed consent and for the generalization of the results of a clinical trial . This paper describes the development and initial application of methods design ed to detect such differences . Developmental work involved creating an inventory of instruments design ed to determine patients ' attitudes towards participating in treatment decision making , permitting r and om selection of treatment , and undertaking the risks and benefits associated with the various treatments in a trial . Initial application involved modifying these instruments in terms of an actual chemotherapeutic trial for colonic adenocarcinoma , seeking responses to these measures from 60 non-eligible colorectal cancer patients , then determining whether those who would agree to trial entry differed systematic ally on these measures from those who indicated that they would refuse such a trial . Twenty-five of the respondents reported that , if faced with the actual decision , they would agree to trial entry : 35 would refuse . Refusers dem and ed more participation in decision making ( Chi-square ; P = 0.01 ) and a greater increment in treatment benefit ( t-test ; P = 0.0001 ) . Twenty-two of the 35 refusers reported aversion to r and omization as their primary reason for trial refusal . Since their particular content can be modified , these measures may be applicable to all clinical trials . They could be used to study the reasons patients accept or refuse trial entry and to determine if agreer-refuser attitude differences undermine the generalizability of a trials results To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied . The study was a single blind observer blinded trial , and patients were paired according to sex , age , and hospital environment . R and omisation assigned the first patient of each pair to the control group ( without informed consent ) or the group to give informed consent . Of the 56 patients , 26 refused to give informed consent , and the age and sex distribution of these differed significantly ( p less than 0.02 ) from the 30 pairs of patients ultimately enrolled into the study . In this " biased " sample , the hypnotic activity of placebo was significantly higher in the control group ( p less than 0.05 ) . It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability Background Despite the increasing dem and for acupuncture and homoeopathy in Germany , little is known about the effects of these treatments in routine care . We set up a pragmatic documentation study in general practice funded within the scope of project launched by a German health insurer . Patients were followed-up for up to four years . Methods The aim of the project was to study the effects and benefits of acupuncture and /or homoeopathy , and to assess patient satisfaction within a prospect i ve documentation of over 5000 acupuncture and over 900 homoeopathy patients . As data sources , we used the documentation made available by therapists on every individual visit and a st and ardised quality -of-life question naire ( MOS SF-36 ) ; these were complemented by questions concerning the patient 's medical history and by questions on patient satisfaction . The health insurer provided us with data on work absenteeism . Results Descriptive analyses of the main outcomes showed benefit of treatment with middle to large-sized effects for the quality of life question naire SF-36 and about 1 point improvement on a rating scale of effects , given by doctors . Data on the treatment and the patients ' and physicians ' background suggests chronically ill patients treated by fairly regular schemes . ConclusionS ince the results showed evidence of a subjective benefit for patients from acupuncture and homoeopathy , this may account for the increase in dem and for these treatments especially when patients are chronically ill and unsatisfied with the conventional treatment given previously QUESTIONS UNDER STUDY To date most of the published studies on the effectiveness of complementary therapies in cancer patients have yielded controversial results because of question able methodology . Research strategies and method ologies acceptable to both conventional and unconventional medicine are difficult to find due to different belief systems . In this publication we describe the development and implementation of a project conducted as part of National Research Programme 34 ( NFP 34 ) . Detailed analysis of our experiences might provide some information on how to deal with practical difficulties in the planning and conduct of further research projects in this field . The project involved the anthroposophical Lukas Clinic in Arlesheim and the Institute of Medical Oncology of the University Hospital , Berne . This interdisciplinary research project was devised to study the relative merits of these two schools of medicine in the care of advanced cancer patients . The project was made up of three components : ( 1 ) a registration study aim ed at comparing the case mix at the two institutions ; ( 2 ) a three armed r and omised study on the effectiveness of supportive therapy , comparing anthroposophy to psychosocial group therapy , and ( 3 ) a longitudinal study to monitor the evaluation of quality of life of patients at the anthroposophical clinic . METHODS After a brief review of the study protocol , which presents the theoretical framework of the project , problems of its implementation are described . Aspects of accrual , acceptance of r and omisation and data availability are presented using simple descriptive statistics and logistic regression . RESULTS The registration study was duly completed with a total of 567 patients . For several reasons ( not meeting inclusion requirements , high refusal rate ) the accrual into the r and omised study was slower than expected and required modification of the original design specifications with regard to inclusion criteria and data collection schedule . Additionally , a high dropout rate contributed to premature closure of this part of the project . The longitudinal study also suffered from low data availability at follow up . CONCLUSIONS The study protocol constituted a major effort at compromise without loss of scientific rigour , and this effort demonstrates that it is possible to allow for different views on patients , on clinical interventions and on research strategies when establishing collaboration between different schools of medicine . Despite a theoretically sound framework , the r and omised part of the project proved difficult in its practical execution . Some unexpected logistical constraints and some unmet expectations influenced the feasibility of this part of the project . Therefore , careful planning of research projects in this field of medicine should always include an extended analysis of various practical aspects of study implementation BACKGROUND Our aim was to assess the efficacy of a part-st and ardised verum acupuncture procedure , in accordance with the rules of traditional Chinese medicine , compared with that of part-st and ardised sham acupuncture and st and ard migraine prophylaxis with beta blockers , calcium-channel blockers , or antiepileptic drugs in the reduction of migraine days 26 weeks after the start of treatment . METHODS This study was a prospect i ve , r and omised , multicentre , double-blind , parallel-group , controlled , clinical trial , undertaken between April 2002 and July 2005 . Patients who had two to six migraine attacks per month were r and omly assigned verum acupuncture ( n=313 ) , sham acupuncture ( n=339 ) , or st and ard therapy ( n=308 ) . Patients received ten sessions of acupuncture treatment in 6 weeks or continuous prophylaxis with drugs . Primary outcome was the difference in migraine days between 4 weeks before r and omisation and weeks 23 - 26 after r and omisation . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N52683557 . FINDINGS Of 1295 patients screened , 960 were r and omly assigned to a treatment group . Immediately after r and omisation , 125 patients ( 106 from the st and ard group ) withdrew their consent to study participation . 794 patients were analysed in the intention-to-treat popoulation and 443 in the per- protocol population . The primary outcome showed a mean reduction of 2 .3 days ( 95 % CI 1.9 - 2.7 ) in the verum acupuncture group , 1.5 days ( 1.1 - 2.0 ) in the sham acupuncture group , and 2.1 days ( 1.5 - 2.7 ) in the st and ard therapy group . These differences were statistically significant compared with baseline ( p<0.0001 ) , but not across the treatment groups ( p=0.09 ) . The proportion of responders , defined as patients with a reduction of migraine days by at least 50 % , 26 weeks after r and omisation , was 47 % in the verum group , 39 % in the sham acupuncture group , and 40 % in the st and ard group ( p=0.133 ) . INTERPRETATION Treatment outcomes for migraine do not differ between patients treated with sham acupuncture , verum acupuncture , or st and ard therapy BACKGROUND Because the value of popular forms of alternative care for chronic back pain remains uncertain , we compared the effectiveness of acupuncture , therapeutic massage , and self-care education for persistent back pain . METHODS We r and omized 262 patients aged 20 to 70 years who had persistent back pain to receive Traditional Chinese Medical acupuncture ( n = 94 ) , therapeutic massage ( n = 78 ) , or self-care educational material s ( n = 90 ) . Up to 10 massage or acupuncture visits were permitted over 10 weeks . Symptoms ( 0 - 10 scale ) and dysfunction ( 0 - 23 scale ) were assessed by telephone interviewers masked to treatment group . Follow-up was available for 95 % of patients after 4 , 10 , and 52 weeks , and none withdrew for adverse effects . RESULTS Treatment groups were compared after adjustment for prer and omization covariates using an intent-to-treat analysis . At 10 weeks , massage was superior to self-care on the symptom scale ( 3.41 vs 4.71 , respectively ; P = .01 ) and the disability scale ( 5.88 vs 8.92 , respectively ; P<.001 ) . Massage was also superior to acupuncture on the disability scale ( 5.89 vs 8.25 , respectively ; P = .01 ) . After 1 year , massage was not better than self-care but was better than acupuncture ( symptom scale : 3.08 vs 4.74 , respectively ; P = .002 ; dysfunction scale : 6.29 vs 8.21 , respectively ; P = .05 ) . The massage group used the least medications ( P<.05 ) and had the lowest costs of subsequent care . CONCLUSIONS Therapeutic massage was effective for persistent low back pain , apparently providing long-lasting benefits . Traditional Chinese Medical acupuncture was relatively ineffective . Massage might be an effective alternative to conventional medical care for persistent back pain Background : Distant healing as a treatment modality is frequently used by patients and healers . Some preliminary evidence suggests possible effects . Since patients suffering from multiple chemical sensitivity and chronic fatigue syndrome have only few effective treatment options , distant healing will be offered as a treatment within a formal trial of distant healing . Design and Method : A four-armed r and omized trial will include 400 patients with self-attributed , environmental problems who fulfil the diagnostic criteria of severe idiopathic chronic fatigue , chronic fatigue syndrome or multiple chemical sensitivity . Patients will be recruited by specialized general practitioners and environmental clinics . They will be treated by healers distributed all over Europe , coming from various healing traditions and nationalities . Each patient will be treated by 3 healers . Healers will have no contact with the patients and will only be provided with the patient ’s Christian name and a photograph . The patients will be r and omized to one of 4 groups in a 2 × 2 factorial design . They will either receive ( distant ) healing or not , and either know or not know this decision . Thereby the effects of expectation and of time can be disentangled from the specific effects of healing . Outcome Measure : Primary outcome measure will be the mental health summary scale of the MOS SF-36 . The measure will be taken at the beginning and at the end of a 6- month treating or waiting period , respectively . A variety of moderator variables will be considered to evaluate which of these may be predictive of outcome BACKGROUND / OBJECTIVES Evidence -based research has been criticized for not being relevant to the real world of patient care in the community , mainly because participants in research studies are dissimilar to those typically seen in every day practice . This article examines recruitment difficulties , and identifies the main reasons why patients with heart failure declined to participate in a research trial . METHODS Postal survey of potential trial participants ( n=667 ) , at time of recruitment . Analysis of ( 1 ) clinical and sociodemographic characteristics of respondents and nonrespondents to survey , and decliners and consenters to participation in a r and omized controlled trial . RESULTS No significant differences were found between respondents and nonrespondents in respect to sociodemographic or clinical variables . Males ( OR=1.58 , CI=1.04 - 2.41 ) , younger patients ( OR=1.05 , CI=1.03 - 1.08 ) , and those prescribed an angiotensin converting enzyme ( ACE ) inhibitor ( OR=1.68 , CI=1.10 - 2.57 ) were significantly more likely to consent to participate . Main reasons for nonparticipation were perceptions of being too old , too unwell , or too busy . CONCLUSIONS Explanations of the purpose of research need to counter against perceptions among participants and clarify the benefits and disadvantages of participating in an intervention study when unwell . Study design should recognize that many elderly patients have busy lives and caring responsibilities . Financial support for participation should be considered Summary 138 psychoneurotic out patients manifesting anxiety were treated for 6 weeks with medication and brief , supportive interviews every 2 weeks with a psychiatric resident . The patients were divided among 12 different treatment conditions composed of 1 . meprobamate 1,600 mg q.i.d . versus an identical placebo in a double-blind arrangement , 2 . a doctor expressing an enthusiastic attitude toward the medication versus a doctor expressing a skeptical attitude toward the medication and 3 . three different psychiatric outpatient clinics . The patient 's symptomatic condition was assessed at each visit by means of five ratings made by the patient before each interview and three ratings made by his doctor afterward . These ratings included an overall judgment of change , a checklist of 64 common symptoms , a score based on the patient 's presenting complaints and adjective checklists for registering anxiety and depression . The results at one clinic showed the expected interaction between medication and doctor 's expressed attitude : with the enthusiastic doctors , patients taking meprobamate improved more than patients taking placebo ; whereas with the skeptical doctors , patients taking placebo tended to improve more than patients taking meprobamate . At the other two clinics , however , this interaction was absent or possibly reversed , with meprobamate tending to be superior to placebo with skeptical doctors . Some striking clinic differences among the characteristics of patients were found , particularly in social class status and the commonly associated styles of complaint and goals and expectations regarding treatment . The clinic showing the anticipated interaction between medication and doctor 's verbal attitude had patients with the lowest social class st and ing . The doctors at this clinic also came from background s of lower social class than the doctors at the other two clinics . These differences suggest that the participants at this clinic may have assigned meanings to the enthusiastic and the skeptical attitudes contrasting with the meanings assigned at the other two clinics . The possible relevenace of these differences to the results is discussed BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as compared with an odds ratio of 0.50 ( 95 percent confidence interval , 0.39 to 0.65 ) from 10 case-control studies . In addition , the range of the point estimates for the effect of vaccination was wider for the r and omized , controlled trials ( 0.20 to 1.56 ) than for the observational studies ( 0.17 to 0.84 ) . CONCLUSIONS The results of well- design ed observational studies ( with either a cohort or a case-control design ) do not systematic ally overestimate the magnitude of the effects of treatment as compared with those in r and omized , controlled trials on the same topic Study Design . A sub analysis of data derived from a r and omized clinical trial was performed . Objective . To evaluate the association of a patient ’s expectation for benefit from a specific treatment with improved functional outcome . Summary of Background Data . Psychosocial factors , ambiguous diagnoses , and lack of a clearly superior treatment have complicated the management of patients with chronic low back pain . The authors hypothesized that patient expectation for benefit from a specific treatment is associated with improved functional outcomes when that treatment is administered . Methods . In a r and omized trial , 135 patients with chronic low back pain who received acupuncture or massage were studied . Before r and omization , study participants were asked to describe their expectations regarding the helpfulness of each treatment on a scale of 0 to 10 . The primary outcome was level of function at 10 weeks as measured by the modified Rol and Disability scale . Results . After adjustment for baseline characteristics , improved function was observed for 86 % of the participants with higher expectations for the treatment they received , as compared with 68 % of those with lower expectations ( P = 0.01 ) . Furthermore , patients who expected greater benefit from massage than from acupuncture were more likely to experience better outcomes with massage than with acupuncture , and vice versa ( P = 0.03 ) . Conclusions . The results of this study suggest that patient expectations may influence clinical outcome independently of the treatment itself . In contrast , general optimism about treatment , divorced from a specific treatment , is not strongly associated with outcome . These results may have important implication s for clinical trial design and recruitment , and may help to explain the apparent success of some conventional and alternative therapies in trials that do not control for patient expectations . The findings also may be important for therapy choices made in the clinical setting The view is widely held that experimental methods ( r and omised controlled trials ) are the " gold st and ard " for evaluation and that observational methods ( cohort and case control studies ) have little or no value . This ignores the limitations of r and omised trials , which may prove unnecessary , inappropriate , impossible , or inadequate . Many of the problems of conducting r and omised trials could often , in theory , be overcome , but the practical implication s for research ers and funding bodies mean that this is often not possible . The false conflict between those who advocate r and omised trials in all situations and those who believe observational data provide sufficient evidence needs to be replaced with mutual recognition of the complementary roles of the two approaches . Research ers should be united in their quest for scientific rigour in evaluation , regardless of the method used Summary A new sequential test has been used to compare the effect of paracetamol and placebo on uterine cramping . Paracetamol was significantly superior to placebo at the 5 % level . 75 patients were included in the trial , whereas in a fixed sample study 90 patients would have been required to obtain the same significance level and power . The magnitude of the difference in treatment effect was estimated following the sequential test . In addition to the effect on uterine pain , which was the primary variable , the effect on episiotomy pain was also estimated . Paracetamol was also superior to placebo against the episiotomy pain We examined recruitment to an imaginary trial of hormone replacement therapy ( HRT ) following two different styles of information about HRT . We predicted that for treatments which , like HRT , are available outside a trial , people offered the facts as currently known would be less likely to remain unsure about the relative costs and benefits , and so less likely to agree to enter a r and omised trial . In contrast , when the information provided reflected the current state of uncertainty which justified the trial , we predicted that people would be less likely to form a preference for one treatment arm over the other , and so more likely to agree to enter a trial . One hundred women aged 25 - 40 years were informed about HRT via a video and an information leaflet . For half the participants the information was framed in a way which emphasised the current state of uncertainty about the relative costs and benefits of HRT , and in that respect it reflected the justification for a trial . This version was considered to be similar in style to information commonly provided to potential trial participants . For half the participants the same information was framed in a way which offered explicit numerical detail about currently known facts , and in that respect it was considered to be similar in style to information commonly available to doctors prior to a trial . Women learned as much about HRT in the two conditions , but women given the explicit versions were more likely ( i ) to hold a stronger view about whether or not they would take HRT ( ratings were not elicited from the first 30 participants in this condition . N = 20 , p < 0.05 1 tailed ) and ( ii ) to refuse entry to the trial ( N = 50 , p < 0.05 2 tailed ) . Those who , given the explicit version , agreed rather than refused to enter the trial , scored higher on believing that others control their health ( p < 0.01 2 tailed ) It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems . The rostral anterior cingulate cortex ( rACC ) and the brainstem are implicated in opioid analgesia , suggesting a similar role for these structures in placebo analgesia . Using positron emission tomography , we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC . We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia , but not during the pain-only condition . These findings indicate a related neural mechanism in placebo and opioid analgesia |
2,130 | 25,900,802 | Due to this lack of information , it is difficult to determine whether or not reportedly successful interventions are feasible and sustainable in an uncontrolled , real-world setting . | CONTEXT An identified limitation of existing review s of physical activity interventions in school-aged youth is the lack of reporting on issues related to the translatability of the research into health promotion practice . | Background Ageing is associated with a decrease in physical activity . This decrease particularly occurs during specific transitional life stages . Especially during adolescence and young adulthood a steep decrease in physical activity is observed . Inactive people are often not aware of their inactivity . Providing feedback on the actual physical activity level by an activity monitor can increase awareness and may in combination with an individually tailored physical activity advice stimulate a physically active lifestyle . Methods In a r and omized controlled trial the effectiveness of providing an activity monitor in combination with a personal physical activity advice through the Internet will be examined . Outcome measures are level of physical activity , determinants of physical activity , quality of life , empowerment , aerobic fitness and body composition . Participants are relatively inactive adolescents and young adults who are measured at baseline , after 3 months intervention and 5 months after the end of the intervention . In addition , facilitating and hindering factors for implementation of the intervention will be investigated . Discussion The use of a personal activity monitor in combination with web-based assisted individually tailored health promotion offers a good opportunity to work interactively with large groups of adolescents and young adults and provide them with advice based on their actual activity level . It has great potential to motivate people to change their behaviour and to our knowledge has not been evaluated before A r and omised control trial evaluated the effectiveness of a theory-based persuasive leaflet design ed to encourage students to undertake at least one additional physical exercise session a week . Participants were 503 secondary school students attending a school in South-East Engl and . The leaflet was written to target potentially modifiable cognitive antecedents of exercise specified by the Theory of Planned Behaviour . It was separately augmented with two cognitive change techniques , result ing in three intervention conditions , leaflet alone ; leaflet plus motivational quiz , and leaflet plus implementation intention prompt , as well as a no-leaflet control condition . Cognitions and behaviour were measured immediately before and 3 weeks after intervention . The results showed that all three-leaflet interventions significantly increased reported exercise , intention to exercise and related cognitions , compared to the control condition , but did not differ in their impact . Mediation analysis showed that intervention effects on exercise were partially mediated by intentions and perceived behavioural control PURPOSE The present study investigates the effect of the Activ-O-Meter , an internet-based computer-tailored physical activity intervention in adolescents in six European centers involved in the HELENA study . METHODS Adolescents ( 12 - 17 years old ) from Vienna , Ghent , Heraklion , Dortmund , Athens , and Stockholm were r and omized into intervention and control schools . Participants in the intervention condition received the computer-tailored advice at baseline and after 1 month . Participants in the control condition received a generic st and ard advice . Effects were evaluated after 1 ( n = 675 ) and 3 months ( n = 494 ) using multi-level modeling . Physical activity levels were measured using the International Physical Activity Question naire for adolescents ( IPAQ-A ) . RESULTS After 1 month , the intervention group reported higher levels of moderate ( beta = -32.8 , 95 % CI ( confidence interval ) : -64.2 to -1.4 ) and vigorous ( beta = -28.0 , 95 % CI : -50.7 to -5.3 ) physical activity in leisure time , as well as higher levels of cycling for transport ( beta = -19.1 , 95 % CI : -34.4 to -7.6 ) compared to the control group . After 3 months , when the intervention group had received the tailored feedback twice , intervention effects were even stronger . Favorable changes in physical activity levels of all intensities and in different context s were found in the tailored group compared to the control group . Among adolescents not reaching the physical activity recommendations at baseline similar effects as in the total sample were found . CONCLUSIONS The data indicated that the computer-tailored physical activity intervention had positive effects on physical activity levels among the adolescents . However , the implementation of the computer-tailored intervention in the schools was not feasible in all countries OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents ( defined as persons between 12 and 14 years of age ) would be successful in influencing body composition and dietary and physical activity behavior in both the short and long terms . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 1108 adolescents ( mean age , 12.7 years ) . Intervention An interdisciplinary program with an adapted curriculum for 11 lessons in biology and physical education and environmental change options . MAIN OUTCOME MEASURES Body height and weight , waist circumference , 4 skinfold thickness measurements , and dietary and physical activity behavior data . RESULTS Multilevel analyses showed that the intervention remained effective in preventing unfavorable increases in important measures of body composition after 20-month follow-up in girls ( biceps skinfold and sum of 4 skinfolds ) and boys ( triceps , biceps , and subscapular skinfolds ) . Consumption of sugar-containing beverages was significantly lower in intervention schools both after intervention ( boys : -287 mL/d ; 95 % confidence interval [ CI ] , -527 to -47 ; girls : -249 ; -400 to -98 ) and at 12-month follow-up ( boys : -233 ; -371 to -95 ; girls : -271 ; -390 to -153 ) . For boys , screen-viewing behavior was significantly lower in the intervention group after 20 months ( -25 min/d ; 95 % CI , -50 to -0.3 ) . No significant intervention effects on consumption of snacks or active commuting to school were found . CONCLUSION The Dutch Obesity Intervention in Teenagers program result ed in beneficial effects on the sum of skinfold thickness measurements in girls and consumption of sugar-containing beverages in both boys and girls in both the short and long terms OBJECTIVE : To evaluate the 6-month impact of a physical activity ( PA ) multilevel intervention on activity patterns and psychological predictors of PA among adolescents . The intervention was directed at changing knowledge and attitudes and at providing social support and environmental conditions that encourage PA of adolescents inside and outside school . SUBJECTS AND DESIGN : R and omised , controlled ongoing field trial ( ICAPS ) in middle-school 's first-level adolescents from eight schools selected in the department of the Bas-Rhin ( Eastern France ) with a cohort of 954 adolescents ( 92 % of the eligible students ) initially aged 11.7±0.6 y. The 6-month changes in participation in leisure organised PA ( LOPA ) , high sedentary ( SED ) behaviour ( > 3h/day ) , self-efficacy ( SELF ) and intention ( INTENT ) towards PA were analysed after controlling for baseline measures and different covariables ( age , overweight , socioprofessional occupation ) , taking into account the cluster r and omisation design . RESULTS : The proportion of intervention adolescents not engaged in organised PA was reduced by 50 % whereas it was unchanged among control students . After adjustment for baseline covariables , LOPA participation significantly increased among the intervention adolescents ( odds ratio ( 95 % confidence interval ) (OR)=3.38 ( 1.42–8.05 ) in girls ; 1.73 ( 1.12–2.66 ) in boys ) , while high SED was reduced ( OR=0.54 ( 0.38–0.77 ) in girls ; 0.52 ( 0.35–0.76 ) in boys ) . The intervention improved SELF in girls , whatever their baseline LOPA ( P<10−4 ) and INTENT in girls with no baseline LOPA ( P=0.04 ) . SELF tended to improve in boys with no baseline LOPA , without reaching statistical significance . When included in the regression , follow-up LOPA was associated with improvement of SELF in girls ( P=0.02 ) and of INTENT in girls with no baseline PA ( P<0.02 ) . The intervention effect was then attenuated . CONCLUSION : After 6 months of intervention , ICAPS was associated with a significant improvement of activity patterns and psychological predictors , indicating a promising approach for modifying the long-term PA level of adolescents Background : Because physical inactivity poses serious health risks , interventions are urgently needed to reverse the increasingly sedentary lifestyles of adolescent girls . Objective : The aim of this study was to determine the feasibility of " Girls on the Move , " an individually tailored computerized physical activity ( PA ) program plus nurse counseling intervention , in increasing PA . Methods : A pretest-posttest control group design was used with 77 racially diverse sedentary girls in Grade s 6 , 7 , and 8 from two middle schools . Each of the instructional grade s was r and omly assigned to either an intervention or control condition . After completing computerized question naires , each girl in the control group received a h and out listing the PA recommendations . To encourage PA , each girl in the intervention group received computerized , individually tailored feedback messages based on her responses to the question naires , individual counseling from the school 's pediatric nurse practitioner ( PNP ) , and telephone calls and mailings from a trained research assistant . At 12 weeks , girls in both groups responded to the question naires . Results : No differences in self-reported PA emerged between the intervention and control groups at Weeks 1 ( baseline ) and 12 ( postintervention ) . Repeated measures ANOVA showed a significant interaction between group and time for social support for PA , F(1 , 69 ) = 5.73 , p = .019 , indicating that the intervention group had significantly greater social support across time than did the control group . From baseline to postintervention , social support increased for the intervention group but decreased for the control group . Discussion : Reasons for the lack of significant differences between the groups on the PA measures were cited . Important information that could inform subsequent studies that test interventions to increase youth PA was acquired from conducting this study . Future efforts to increase PA participation might include this approach for enhancing social support for PA This study examined the effectiveness of an intervention to increase levels of moderate-to-vigorous intensity physical activity ( MVPA ) during girls ' physical education lessons . Two Year 7 classes ( age 11 - 12 years ) were r and omly appointed to control and experimental groups . Both followed the same six-lesson unit of gymnastics with identical lesson objectives . The experimental class teacher included the additional objective of increasing MVPA during each lesson . MVPA was assessed in all six lessons using heart rate ( HR ) monitoring and systematic observation . After each lesson , students ' intrinsic motivation and perceived competence were assessed , and the teachers evaluated whether they had met planned objectives . The experimental group engaged in more MVPA [ F(1 , 21 ) = 8.49 , P = 0.008 ( HR ) , t8 = -2.35 , P = 0.048 ( observation ) ] than the control group and also had most opportunities for skill practice ( t8 = -2.81 , P = 0.023 ) . Intrinsic motivation and perceived competence levels were similar between the groups for each lesson , and teachers reported that lesson objectives were satisfactorily achieved . This intervention succeeded in increasing MVPA without compromising intrinsic motivation , perceived competence or planned lesson objectives OBJECTIVES ICAPS ( Intervention Centred on Adolescents ' Physical activity and Sedentary behaviour ) is aim ed at preventing excessive weight gain and cardiovascular risk in adolescents by promoting physical activity ( PA ) with an emphasis on recreational and daily-life PA , with a lifelong perspective . DESIGN R and omized study design ed to last for four years . Study cohort constituted of 954 first-level students ( 91 % of eligible pupils ) , aged 11.7 + /- 0.6 y ( mean + /- SD ) from four pairs of schools r and omly selected in eastern France , after sociogeographical stratification . In each pair , intervention status was r and omised at school-level . The program , not limited to school setting s , involves multiple partners with three objectives : 1 ) changing attitudes through debates and access to attractive activities during breaks and after-school hours , 2 ) encouraging social support , 3 ) providing environmental conditions that enable PA . Adapted times and places , open participation , emphasis on fun , meeting with others and absence of competitive aspects are used to reduce usual barriers to PA . Accessibility and safety are permanent concerns . RESULTS Prevalence of overweight was 23.7 % . High participation rates were attained ( 50 % participated in at least one weekly activity ) . At six-month , the proportion of intervention adolescents not performing supervised PA out of academic PA was reduced by half ( 36 % to 17 % vs 42 % to 42 % in controls P < 10 - 4 ) ; the proportion of those spending > 3 h/day in sedentary occupations decreased ( 34 % to 28 % vs 27 % to 36 % ; P < 10 - 4 ) . CONCLUSION These data demonstrate the feasibility of implementing a multilevel PA intervention program in adolescents . Six-month results document increased PA and decreased sedentary behaviour BACKGROUND Although adolescence is a time when physical activity levels decline , few interventions have targeted high school-aged girls in the school setting . OBJECTIVE To evaluate the effects of a life skills-oriented physical activity intervention for increasing overall physical activity in high school-aged girls . DESIGN R and omized controlled trial . SETTING Baltimore magnet high school . PARTICIPANTS A total of 221 ninth- grade girls , 83.0 % of whom were African American . Intervention Participants were r and omized to an 8-month physical intervention conducted in physical education class or to a st and ard physical education class ( control ) . MAIN OUTCOME MEASURES Self-reported estimated daily energy expenditure ( physical activity ) , self-reported sedentary activities ( television viewing and computer or Internet use ) , cardiorespiratory fitness , and selected cardiovascular disease risk factors . RESULTS Intervention classes spent 46.9 % of physical education class time in moderate to vigorous activity compared with 30.5 % of time for control classes ( P<.001 ) . There were no significant between-treatment group differences for mean daily energy expenditure ( P = .93 ) , moderate-intensity energy expenditure ( P = .77 ) , or hard to very hard energy expenditure ( P = .69 ) . The proportion of participants who spent 3 or more hours viewing television during school days declined from 22.3 % to 17.0 % in the intervention group , but remained at 26.7 % for the control group ( P = .03 ) . Both groups improved their cardiorespiratory fitness ( P<.001 ) . CONCLUSION A life skills-oriented physical education curriculum may need to be combined with other approaches to increase the magnitude of effects on physical activity behavior in predominantly African American high school-aged girls BACKGROUND Physical activity is important for weight control and good health ; however , activity levels decline in the adolescent years , particularly in girls . DESIGN Group r and omized controlled trial . SETTING / PARTICIPANTS Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States . R and om , cross-sectional sample s were drawn within schools : 6th grade rs in 2003 ( n=1721 ) and 8th grade rs in 2005 ( n=3504 ) and 2006 ( n=3502 ) . INTERVENTION A 2-year study -directed intervention ( fall 2003 to spring 2005 ) targeted schools , community agencies , and girls to increase opportunities , support , and incentives for increased physical activity . Components included programs linking schools and community agencies , physical education , health education , and social marketing . A third-year intervention used school and community personnel to direct intervention activities . MAIN OUTCOME MEASURES The primary outcome , daily MET-weighted minutes of moderate-to-vigorous physical activity ( MET-weighted MVPA ) , was assessed using accelerometry . Percent body fat was assessed using anthropometry . RESULTS After the staff-directed intervention ( pre-stated primary outcome ) , there were no differences ( mean= -0.4 , 95 % CI= -8.2 to 7.4 ) in adjusted MET-weighted MVPA between 8th- grade girls in schools assigned to intervention or control . Following the Program Champion-directed intervention , girls in intervention schools were more physically active than girls in control schools ( mean difference 10.9 MET-weighted minutes of MVPA , 95 % CI=0.52 - 21.2 ) . This difference is about 1.6 minutes of daily MVPA or 80 kcal per week . There were no differences in fitness or percent body fat at either 8th- grade timepoint . CONCLUSION A school-based , community-linked intervention modestly improved physical activity in girls PURPOSE This intervention compares the effectiveness of daily step count targets with time-based prescription for increasing the health-related physical activity of low-active adolescent girls . METHODS We assigned participants ( N = 85 , mean age 15.8 + /- 0.8 yr ) depending on school attended to a control ( CON ) , pedometer ( PED ) , or minutes ( MIN ) group . The intervention groups were involved in a 12-wk physical activity self-monitoring and educative program . The only difference between the intervention groups was that the PED group set daily step count targets whereas the MIN group set daily time-based goals for physical activity involvement . Pre- , mid- , and postintervention changes in physical activity ( 4-d blinded step count and 3-d physical activity recall ) and body mass index ( BMI ) were assessed using a series of 3 ( group assignment ) x 3 ( time ) ANOVA . Where significant interactions were found , separate follow-up simple main effects tests were used . RESULTS At postintervention , only the PED group had significantly increased their total activity as measured by a 4-d step count , when compared with the control ( P = 0.03 , ES = 0.13 ) . The group , time , and interaction effects for 4-d step count were significant , indicating that although both the participants in the PED and the MIN groups significantly increased their step count across the 12-wk intervention ( P = 0.00 - 0.01 ) , the participants in the PED group had a greater increase at the midintervention time point ( P = 0.04 , ES = 0.10 ) . No pre- , mid- , or postintervention changes were reported in any group for BMI ( F = 1.18 , P = 0.32 ) . CONCLUSION The use of pedometers and daily step count targets with low-active adolescent girls may result in short-term ( 6 wk ) enhanced physical activity related outcomes when compared with traditional time-based physical activity prescriptions . However , both interventions appear to result in similar improvements in physical activity when duration of the observation is extended to 12 wk BACKGROUND This study reports on effectiveness trial outcomes of Health in Motion , a computer tailored multiple behavior intervention for adolescents . METHODS Using school as level of assignment , students ( n=1800 ) from eight high schools in four states ( RI , TN , MA , and NY ) were stratified and r and omly assigned to no treatment or a multi-media intervention for physical activity , fruit and vegetable consumption , and limited TV viewing between 2006 and 2007 . RESULTS Intervention effects on continuous outcomes , on movement to action and maintenance stages , and on stability within action and maintenance stages were evaluated using r and om effects modeling . Effects were most pronounced for fruit and vegetable consumption and for total risks across all time points and for each behavior immediately post intervention . Co-variation of behavior change occurred within the treatment group , where individuals progressing to action or maintenance for one behavior were 1.4 - 4.2 times more likely to make similar progress on another behavior . CONCLUSION Health in Motion is an innovative , multiple behavior obesity prevention intervention relevant for all adolescents that relies solely on interactive technology to deliver tailored feedback . The outcomes of the effectiveness trial demonstrate both an ability to initiate behavior change across multiple energy balance behaviors simultaneously and feasibility for ease of dissemination BACKGROUND Our objective was to evaluate the effects of environmental , policy , and social marketing interventions on physical activity and fat intake of middle school students on campus . DESIGN Twenty-four middle schools were r and omly assigned to intervention or control conditions . Baseline measures were collected in spring 1997 , and interventions were conducted during the 1997 - 1998 and 1998 - 1999 school years SETTING /PARTICIPATION : The schools had mean enrollments of 1109 , with 44.5 % nonwhite students . Over 2 years , physical activity interventions were design ed to increase physical activity in physical education classes and throughout the school day . Nutrition interventions were design ed to provide and market low-fat foods at all school food sources , including cafeteria breakfasts and lunches , a la carte sources , school stores , and bag lunches . School staff and students were engaged in policy change efforts , but there was no classroom health education . MAIN OUTCOMES MEASURES Primary outcomes were measured by direct observation and existing records . RESULTS R and omized regression models ( N = 24 schools ) revealed a significant intervention effect for physical activity for the total group ( p < 0.009 ) and boys ( p < 0.001 ) , but not girls ( p < 0.40 ) . The intervention was not effective for total fat ( p < 0.91 ) or saturated fat ( p < 0.79 ) . Survey data indicated that the interventions reduced reported body mass index for boys ( p < 0.05 ) . CONCLUSIONS Environmental and policy interventions were effective in increasing physical activity at school among boys but not girls . The interventions were not effective in reducing fat intake at school . School environmental and policy interventions have the potential to improve health behavior of the student population , but barriers to full implementation need to be better understood and overcome Purpose . Examine the reach , efficacy , adoption , implementation , and maintenance of a physical activity and nutrition curriculum for middle-school students . Design . Nonexperimental pilot evaluation of a statewide dissemination trial . Setting . California middle schools during the 2006 to 2007 school year . Subjects . Sixteen classes ( N = 668 students and 16 teachers ) sample d from the statewide pool who used the program . Intervention . An eight-lesson nutrition and physical activity curriculum , “ Exercise Your Options ” ( EYO ) , including a teacher guide , video clips , a student activity booklet , and ancillary material s was made available to teachers . Measures . Program records , classroom observations , teacher surveys , and student presurveys and postsurveys ( assessing physical activity , sedentary behaviors , and dietary intake ) . Analysis . Descriptive statistics and multilevel r and om-coefficient modeling . Results . The EYO program reached 234 , 442 middle-school students in California . During the program , total physical activity increased ( p ≤ .001 ) , whereas watching TV/DVDs and playing electronic games/computer use decreased ( p ≤ .05 ) . Intake of dairy products increased ( p < .05 ) , whereas consumption of sugars/sweets decreased ( p < .001 ) . Forty-two percent of eligible middle-school classrooms ordered the program material s. Eighty-six percent of sample d teachers implemented all of the lessons . Over the past 5 years , 51 % of all middle-school students in California were exposed to the program . Conclusions . The EYO program showed its potential for moderate to high public health impact among California middle-school students Background In this study the one and six months effects of the computer-tailored YouRAction ( targeting individual level determinants ) and YouRAction+e ( targeting in addition perceived environmental determinants ) on compliance with the moderate-to-vigorous physical activity ( MVPA ) guideline and weight status are examined . In addition the use and appreciation of both interventions are studied . Methods A three-armed cluster r and omized trial was conducted in 2009–2010 with measurements at baseline , one and six months post intervention . School classes were assigned to one of the study arms ( YouRaction , YouRAction+e and Generic Information ( GI ) control group ) . MVPA was derived from self-reports at baseline , one and six months post intervention . Body Mass Index and waist circumference were measured at baseline and six months post intervention in a r and om sub- sample of the population . Use of the interventions was measured by webserver logs and appreciation by self-reports . Multilevel regression analyses were conducted to study the effects of the intervention against the GI control group . ANOVA 's and chi-square tests were used to describe differences in use and appreciation between study arms . Results There were no statistically significant intervention effects on compliance with the MVPA guideline , overweight or WC . Access to the full intervention was significantly lower for YouRAction ( 24.0 % ) and YouRAction+e ( 21.7 % ) compared to the GI ( 54.4 % ) . Conclusion This study could not demonstrate that the YouRAction and YouRAction+e interventions were effective in promoting MVPA or improve anthropometric outcomes among adolescents , compared to generic information . Insufficient use and exposure to the intervention content may be an explanation for the lack of effects . Trial Registration TrialRegister.nl Background Lack of regular physical activity and consequent sub-optimal bone mass acquisition in youth has been implicated as a primary cause of adult-onset osteoporosis . IMPACT was a behavioral theory-based 1 1/2 year r and omized controlled field study aim ed at increasing bone accretion in middle school girls . The objective of this study was to determine the intervention effects of the IMPACT program upon key physical and sedentary activity endpoints among schools that participated in the IMPACT study . Endpoints examined included weight bearing physical activity ( WBPA ) ; moderate to vigorous physical activity ( MVPA ) ; vigorous physical activity ( VPA ) ; MET ( metabolic equivalent ) – weighted WBPA and MVPA ; sedentary activity ; before/after-school physical activity ; and weekend physical activity . Methods Primary data analysis using a pretest-posttest control group design was conducted utilizing mixed model analysis of covariance . Data gathered from the IMPACT cohort from 2000–2002 were analyzed to determine baseline versus follow-up differences in activity endpoints . Confounders investigated included ethnicity , body mass index , menarcheal status , participation in 7th grade PE/athletics , friend/familial support and neighborhood safety . Results Follow-up means were higher for participating intervention schools relative to control schools for all physical activity variables but were statistically significant only for the following variables : daily minutes of vigorous physical activity ( mean difference between Intervention ( I ) and Control ( C ) = 6.00↑ minutes , 95 % CI = 5.82–6.18 , p = 0.05 ) , daily after school activity minutes ( mean difference between I and C = 8.95↑ minutes , 95 % CI = 8.69–9.21 , p = 0.04 ) , and daily weekend activity minutes ( mean difference between I and C = 19.00↑ minutes , 95 % CI = 18.40–19.60 , p = 0.05 ) . The intervention significantly reduced duration of student daily TV/Video watching ( mean difference between I and C = 12.11↓ minutes , 95 % CI = 11.74–12.48 , p = 0.05 ) and total daily sedentary activity minutes ( mean difference between I and C = 16.99↓ minutes , 95 % CI = 16.49–17.50 , p = 0.04 ) . Conclusion A well design ed and implemented school based health and physical activity intervention can result in a positive influence upon increasing physical activity levels and decreasing sedentary activity . Future interventions should consider a more structured intervention component to obtain significant changes in WBPA Background Only limited data are available on the development , implementation , and evaluation processes of weight gain prevention programs in adolescents . To be able to learn from successes and failures of such interventions , integral written and published reports are needed . Methods Applying the Intervention Mapping ( IM ) protocol , this paper describes the development , implementation , and evaluation of the Dutch Obesity Intervention in Teenagers ( DOiT ) , a school-based intervention program aim ed at the prevention of excessive weight gain . The intervention focussed on the following health behaviours : ( 1 ) reduction of the consumption of sugar-sweetened beverages , ( 2 ) reduction of energy intake derived from snacks , ( 3 ) decrease of levels of sedentary behaviour , and ( 4 ) increase of levels of physical activity ( i.e. active transport behaviour and sports participation).The intervention program consisted of an individual classroom-based component ( i.e. an educational program , covering 11 lessons of both biology and physical education classes ) , and an environmental component ( i.e. encouraging and supporting changes at the school canteens , as well as offering additional physical education classes).We evaluated the effectiveness of the intervention program using a r and omised controlled trial design . We assessed the effects of the intervention on body composition ( primary outcome measure ) , as well as on behaviour , behavioural determinants , and aerobic fitness ( secondary outcome measures ) . Furthermore , we conducted a process evaluation . Discussion The development of the DOiT-intervention result ed in a comprehensive school-based weight gain prevention program , tailored to the needs of Dutch adolescents from low socio-economic background OBJECTIVE To identify factors associated with changes in physical activity in adolescent girls at risk for sedentary lifestyles and obesity . DESIGN A cohort study was performed with 201 high school girls recruited to participate in an evaluation study of a school-based obesity prevention physical education program . Three assessment s were performed during an 8-month period . MAIN OUTCOME MEASURES Associations between physical activity and a range of personal factors ( self-acceptance , self-worth , athletic competence , body image , depressive mood , perceived benefits , enjoyment of physical activity , self-efficacy , and body mass index ) , behavioral factors ( watching television and time constraints ) , and socioenvironmental factors ( social support and costs/re sources ) were assessed . RESULTS The 2 strongest and most consistent factors associated with change in physical activity were time constraints and support for physical activity from peers , parents , and teachers . Measures assessing self-perceptions , global ( ie , self-worth ) and specific to physical activity ( ie , self-efficacy to be physically active ) , were also associated with change in physical activity . For example , a decrease of 2.0 U for an adolescent 's perceived time constraints ( possible range , 3.0 - 12.0 U ) would be expected to lead to an increase of 53 minutes of moderate to vigorous physical activity per week ( 95 % confidence interval , 33 - 72 minutes ) . An increase of 2.0 U in perceived support for physical activity ( possible range , 3.0 - 12.0 U ) would be expected to lead to an increase of 35 minutes of moderate to vigorous physical activity per week ( 95 % confidence interval , 13 - 56 minutes ) . An increase of 3.0 U on the self-worth scale ( possible range , 5.0 - 20.0 U ) might be expected to lead to an increase of 19 minutes of moderate to vigorous physical activity per week ( 95 % confidence interval , 0 - 40 minutes ) . CONCLUSION The effectiveness of interventions aim ed at increasing physical activity among adolescent girls might be enhanced by engaging support from friends , family , and caring adults ; addressing real and perceived time constraints ; and helping adolescent girls feel more confident about themselves and their ability to engage in physical activity OBJECTIVE To evaluate the effects of a 2-year middle school physical activity and healthy food intervention , including an environmental and computer-tailored component on BMI and BMI z-score in boys and girls . RESEARCH METHODS AND PROCEDURES A r and om sample of 15 schools with seventh and eighth grade rs was r and omly assigned to three conditions : an intervention with parental support group , an intervention-alone group , and a control group . Weight and height were measured at the beginning and end of each school year to assess BMI and BMI z-score . A physical activity and healthy food program was implemented over 2 school years . RESULTS In girls , BMI and BMI z-score increased significantly less in the intervention with parental support group compared with the control group ( p < 0.05 ) or the intervention-alone group ( p = 0.05 ) . In boys , no significant positive intervention effects were found . DISCUSSION This was the first study evaluating the effectiveness of an intervention combining environmental changes with personal computer-tailored feedback on BMI and BMI z-score in middle school children . After 2 school years , BMI and BMI z-score changed in a more positive direction in girls as a result of the intervention with parental support The primary purpose of this study was to test the efficacy of a brief , multi-health behavior intervention integrating physical activity and alcohol use prevention messages for high school-aged adolescents . A total of 604 participants , 335 9th and 269 11th grade students from a suburban high school in northeast Florida participated in this study . A r and omized control trial was conducted with participants r and omly assigned within grade levels to receive either a brief consultation and prescription with a mailed reinforcing follow-up flyer ( Project SPORT ) or a minimal intervention control consisting of a wellness brochure provided in school and a pamphlet about teen health and fitness mailed to the home . Differences between intervention groups were evaluated with a series of MANCOVA tests . Project SPORT participants demonstrated significant positive effects at 3-months postintervention for alcohol consumption , alcohol initiation behaviors , alcohol use risk and protective factors , drug use behaviors , and exercise habits , and at 12-months for alcohol use risk and protective factors , cigarette use , and cigarette initiation ( p 's < 0.05 ) . A post hoc analysis examining interactions between past 30-day use of marijuana and /or cigarettes by treatment group indicates significant positive effects for drug using adolescents who received Project SPORT on alcohol consumption , drug use behaviors , and drug use initiation at 3-months , and for drug use behaviors and exercise habits at 12-months ( p 's < 0.05 ) . A brief , 12-min one-on-one consultation integrating alcohol avoidance messages within those promoting fitness and other positive health behaviors holds promise for influencing adolescent alcohol and cigarette use and other health behaviors at posttreatment and 1 year later . Long-term sustained effects for cigarette and marijuana use , and both vigorous and moderate physical activity , were found among adolescents using marijuana and /or cigarettes prior to intervention PURPOSE The objective of this study was to evaluate the impact of a school-based intervention ( Program X ) incorporating pedometers and e-mail support on physical activity , sedentary behavior , and healthy eating in adolescents . METHODS A r and omized control trial was used to evaluate the impact of the Program X intervention . Six schools ( N = 124 participants ; mean age 14.1 + /- .8 years ) were r and omized to intervention or control conditions for the 6-month study period . Objective ly recorded physical activity ( mean steps/day ) , self-reported sedentary behavior , and dietary habits were measured at baseline and at 6-month follow-up and intervention effects were assessed using repeated- measures analysis of variance and chi(2 ) tests . RESULTS Participants in the intervention group increased their step counts by 956 + /- 4107 steps/day ( boys ) and 999 + /- 1999 ( girls ) . Repeated- measures analysis of variance revealed significant group-by-time interactions for boys ( F = 7.4 , p = .01 , d = .80 ) and girls ( F = 29.6 , p < .001 , d = 1.27 ) for mean steps/day . The intervention significantly decreased the number of energy-dense/low-nutrient snacks consumed by boys ( chi(2 ) = 4.0 , p = .043 ) and increased the number of fruit serves among girls ( chi(2 ) = 4.8 , p = .028 ) . The intervention did not have a statistically significant effect on sedentary behavior . CONCLUSION A school-based intervention incorporating physical activity monitoring using pedometers and e-mail support was successful in promoting physical activity and selected healthy eating behaviors in adolescent boys and girls OBJECTIVES We sought to assess the effects of a school-based intervention program on cardiovascular disease risk factors in urban girls . METHODS We compared heart health knowledge , health behaviors , cardiovascular risk factors , and physical fitness among a group of 442 multiethnic teenaged girls ( 310 experimental participants vs 132 control participants ) . Testing was conducted before and after a 12-week program of vigorous exercises integrated with lectures and discussion s on diet , exercise , stress , and smoking . RESULTS Significant differences in body fat , systolic and diastolic blood pressure , heart health knowledge , and whether breakfast was eaten were observed between experimental participants and control participants . CONCLUSIONS An integrated program of exercise and heart health-related lectures and discussion s had a beneficial effect on health knowledge , health behaviors , and onset of risk factors for coronary artery disease among urban girls This study tested the potential of a novel intervention addressing alcohol prevention within the context of a sport program . Study participants were r and omly assigned to one of three groups , with one group receiving the sport consultation ( Sport ) , a second the sport consultation plus an alcohol consultation ( Sport Plus ) , and a third a sport consultation , alcohol consultation , and mailed parent print material s ( Sport Plus Parent ) . Research ers recruited 465 eighth grade rs from three schools in the northeast Florida region to participate in the study . The Youth Alcohol and Health Survey was used to collect data on alcohol and drug consumption , alcohol use risk and protective factors , and exercise habits at baseline and three-month post-intervention . Significant time effects ( p 's < .05 ) were found on three of six alcohol measures , both exercise measures , and four risk/protective factors , with all but one risk factor showing improvements over time . Time by assignment by current drinking status ( yes/no ) interaction effects ( p 's < .05 ) were found on alcohol initiation , length of alcohol use , quantity , heavy use , moderate physical activity , and four risk/protective factors , with preintervention drinking adolescents exposed to the Sport intervention showing the greatest improvements on all but two measures . Findings suggest that a brief sport-based screen and consultation tailored to adolescents ' health habits , with and without parent material s , may potentially reduce alcohol use while increasing exercise frequency OBJECTIVE To assess the feasibility , acceptability , and potential efficacy of a school-based obesity prevention program among adolescent boys with sub-optimal cardiorespiratory fitness . METHODS In 2007 , a 6-month , 2-arm parallel group , r and omized controlled pilot trial was conducted in a single school setting ( Sydney , Australia ) . Thirty-three 7th Grade boys ( mean age=12.5+/-0.4 years ) were r and omly assigned to intervention ( n=16 ) or active comparison group ( n=17 ) . The intervention consisted of one 60-minute curriculum session and two 20-minute lunchtime physical activity sessions per week . The active comparison group continued with their usual physical activity curriculum sessions ( Friday afternoons 2 - 3 pm ) . The pilot trial 's curriculum sessions were additional to Physical Education ( PE ) lessons . The primary outcome was BMI , and secondary outcomes included waist circumference , percentage body fat , cardiorespiratory fitness , objective ly measured physical activity and small screen recreation time . RESULTS Screening , recruitment and retention goals were exceeded . The majority of data were collected as planned . Implementation and attendance rates were acceptable . At follow-up , compared with boys in the active comparison group , boys in the intervention group displayed a smaller increase in BMI ( adjust diff.=-0.2 , 95 % confidence interval [ CI ] -0.78 , 0.39 ; Cohen 's d=0.05 ) ; greater reductions in waist circumference ( -1.65 cm [ -4.67 , 1.36 ] ; d=0.15 ) ; percentage body fat ( -1.69 % [ -4.98 , 1.60 ] ; d=0.22 ) and time spent in small screen recreation on weekends ( -1.13 h [ -5.06 , 2.80 ] ; d=0.19 ) ; and a greater increase in cardiorespiratory fitness ( 2.13 laps [ 6.22 , 10.48 ] ; d=0.16 ) ; and participation in total weekday physical activity ( 140.74 counts/min [ -159.44 , 440.92 ] ; d=0.36 ) . CONCLUSIONS This study verified the feasibility , acceptability and potential efficacy of a multifaceted school-based intervention to prevent unhealthy weight gain among adolescent boys OBJECTIVE To evaluate the feasibility and effectiveness of a 3-month minimal physical activity ( PA ) intervention in adolescents . METHODS A r and omised controlled trial , including five secondary schools ( n=87 ) . In the 3-month intervention ( Amsterdam , The Netherl and s , 2005 ) adolescents were provided with a PAM accelerometer , coupled to a web-based tailored PA advice ( PAM COACH ) . Measurements ( i.e. , PA , determinants of PA , aerobic fitness and anthropometrics ) took place at baseline and at 3- and 8-month follow-up . RESULTS Sixty-five percent of the participants in the intervention group reported to have worn the PAM frequently and 56 % of the PAM users uploaded their PAM scores to the PAM COACH at least once . We found significant differences between groups in favour of the intervention group in moderate intensity PA ( MPA ) for girls after 3 months ( 411 min/week ; 95 % CI : 1 ; 824 ; P=0.04 ) and in sedentary time for boys after 8 months ( -1801 min/week ; 95 % CI : -3545 ; -57 ; P=0.04 ) . CONCLUSIONS Although the process evaluation suggests that a substantial proportion of the participants did not regularly wear the PAM and did not upload information to the PAM COACH website , our findings suggest promising intervention effects on MPA among girls and sedentary time among boys BACKGROUND Many female adolescents participate in insufficient physical activity to maintain cardiovascular fitness and promote optimal bone growth . This study evaluates the impact of a school-based intervention on fitness , activity , and bone among adolescent females . METHODS Subjects were assigned to an intervention ( n = 63 ) or comparison ( n = 59 ) group , and underwent assessment s of cardiovascular fitness ( VO2peak ) , physical activity , body composition , bone mineral density ( BMD ) , bone mineral content ( BMC ) , and serum markers of bone turnover at baseline and at the end of each of two school semesters . RESULTS The intervention increased physical activity , VO2peak , and BMC for the thoracic spine ( P values < 0.05 ) . Bone turnover markers were not affected . In longitudinal analyses of the combined groups , improvements in cardiovascular fitness predicted increased bone formation ( P < 0.01 ) and bone resorption ( P < 0.05 ) . CONCLUSION A school-based intervention for adolescent females effectively increased physical activity , cardiovascular fitness , and thoracic spine BMC PURPOSE To compare the effectiveness of a Web-based physical activity ( PA ) intervention with identical content delivered in a printed workbook among a sample of adolescent girls . METHODS Participants consisted of 319 girls with home Internet access enrolled in four middle schools within one school district . A r and omized trial design was used to compare changes in PA self-efficacy and intentions after two weeks of exposure to either a Web- or print-based intervention delivered to their home . Self-reported physical activity was assessed as a secondary outcome . Analysis of covariance was conducted to determine changes between the intervention groups while controlling for baseline levels of PA constructs . RESULTS Both Web and print groups had significant changes in physical activity self-efficacy ( Web : t[155 ] = 2.58 , p = .01 ; print : t[156 ] = 3.11 , p = .002 ) and intentions ( Web : t[157 ] = 2.27 , p = .02 ; print : t[159 ] = 6.32 , p < or = .001 ) . The print group demonstrated significantly greater increases in intentions compared with the Web group ( F [ 1,315 ] = 13.53 , p < or = .001 ) . Self-reported physical activity increased significantly in the print group only ( t[159 ] = 3.21 , p = .002 ) . CONCLUSIONS It can not be assumed that new media technologies are superior to traditional media such as print for health communication to adolescents . These results suggest that a printed workbook was more effective than an identical website for increasing physical activity intentions and behavior among a sample of middle school girls BACKGROUND This study evaluated the effects of the Lifestyle Education for Activity Program ( LEAP ) , a comprehensive school-based intervention emphasizing changes in instruction and school environment , on variables derived from social-cognitive theory ( SCT ) as mediators of change in physical activity among black and white adolescent girls . METHODS Twenty-four high schools paired on enrollment size , racial composition , urban , suburban , or rural location , and class structure were r and omized into control ( n = 12 ) or experimental ( n = 12 ) groups . There were 1038 girls in the control group and 1049 girls in the experimental group . The multicomponent intervention emphasized the enhancement of self-efficacy and development of behavioral skills by using curricular activities within physical education classes and health education instruction . The primary outcomes were self-efficacy , outcome -expectancy value , goal setting , satisfaction , and physical activity . RESULTS Latent variable structural equation modeling indicated that : ( 1 ) self-efficacy and satisfaction exhibited synchronous , cross-sectional relationships with physical activity ; ( 2 ) the intervention had direct effects on self-efficacy , goal setting , and physical activity ; and ( 3 ) self-efficacy partially mediated the effect of intervention on physical activity . CONCLUSIONS To our knowledge , this study provides the first evidence from a r and omized controlled trial that manipulation of self-efficacy results in increased physical activity among black and white adolescent girls . The results encourage the use of self-efficacy as a targeted , mediator variable in interventions design ed to increase physical activity among girls Rates of chronic diseases are high among Black South Africans but few studies have tested cognitive-behavioural health-promotion interventions to reduce this problem . We tested the efficacy of such an intervention among adolescents in a cluster-r and omised controlled trial . We r and omly selected 9 of 17 matched pairs of schools and r and omised one school in each pair to the cognitive-behavioural health-promotion intervention design ed to encourage health-related behaviours and the other to a human immunodeficiency virus (HIV)/sexually transmitted disease ( STD ) risk-reduction intervention that served as the control . Interventions were based on social cognitive theory , the theory of planned behaviour and qualitative data from the target population . Data collectors , blind to participants ’ intervention , administered confidential assessment s at baseline and 3 , 6 and 12 months post-intervention . Primary outcomes were fruit and vegetable consumption and physical activity . Participants were 1057 grade 6 learners ( mean age = 12.4 years ) , with 96.7 % retained at 12-month follow-up . Generalised estimating equations revealed that averaged over the follow-ups , a greater percentage of health-promotion intervention participants than HIV/STD control participants met 5-a-Day fruit and vegetable and physical activity guidelines . The intervention also increased health-promotion knowledge , attitude and intention , but did not decrease substance use or substance-use attitude and intention . The findings suggest that theory based and context ually appropriate interventions may increase health behaviours among young adolescents in sub-Saharan Africa PURPOSE School physical education ( PE ) is highly recommended as a means of promoting physical activity , and r and omized studies of health-related PE interventions in middle schools have not been reported . We developed , implemented , and assessed an intervention to increase physical activity during middle-school PE classes . METHODS Twenty-four middle schools ( approximately 25,000 students , 45 % nonwhite ) in Southern California participated in a r and omized trial . Schools were assigned to intervention ( N = 12 ) or control ( N = 12 ) conditions , and school was the unit of analysis . A major component of the intervention was a 2-yr PE program , which consisted of curricular material s , staff development , and on-site follow-up . Control schools continued usual programs . Student activity and lesson context were observed in 1849 PE lessons using a vali date d instrument during baseline and intervention years 1 and 2 . RESULTS The intervention significantly ( P = 0.02 ) improved student moderate to vigorous physical activity ( MVPA ) in PE , by approximately 3 min per lesson . Effects were cumulative ; by year 2 intervention schools increased MVPA by 18 % . Effect sizes were greater for boys ( d = 0.98 ; large ) than girls ( d = 0.68 ; medium ) . CONCLUSIONS A st and ardized program increased MVPA in middle schools without requiring an increase in frequency or duration of PE lessons . Program components were well received by teachers and have the potential for generalization to other schools . Additional strategies may be needed for girls PURPOSE To evaluate the effects of a middle school physical activity intervention , new in combining an environmental and computer tailored component ; and to evaluate the effects of parental involvement . METHODS A clustered r and omized controlled design was used . A r and om sample of 15 schools with 7th and 8th grade rs was r and omly assigned to one of three conditions : ( a ) intervention with parental support , ( b ) intervention alone , and ( c ) control group . The intervention was new in combining environmental strategies with computer-tailored feedback to increase levels of moderate to vigorous physical activity . The intervention was implemented by the school staff . Physical activity was measured through a question naire in the total sample and with accelerometers in a sub sample of adolescents . RESULTS The intervention with parental support led to an increase in self-reported school-related physical activity of , on average , 6.4 minutes per day ( p < or = .05 , d = .40 ) . Physical activity of light intensity measured with accelerometers decreased with , on average , 36 minutes per day as a result of the intervention with parental support ( p < or = .05 , d = .54 ) . Physical activity of moderate to vigorous intensity measured with accelerometers significantly increased with on average 4 minutes per day in the intervention group with parental support , while it decreased with almost 7 minutes per day in the control group ( p < or = .05 , d = .46 ) . CONCLUSIONS The physical activity intervention , implemented by the school staff , result ed in enhanced physical activity behaviors in both middle school boys and girls . The combination of environmental approaches with computer-tailored interventions seemed promising OBJECTIVES : The objective of this study was to evaluate a 12-session home/community-based health promotion/obesity prevention program ( Challenge ! ) on changes in BMI status , body composition , physical activity , and diet . METHODS : A total of 235 black adolescents ( aged 11–16 years ; 38 % overweight/obese ) were recruited from low-income urban communities . Baseline measures included weight , height , body composition , physical activity ( PA ) , and diet . PA was measured by 7-day play-equivalent physical activity ( ≥1800 activity counts per minute ) . Participants were r and omly assigned to health promotion/obesity prevention that is anchored in social cognitive theory and motivational interviewing and was delivered by college-aged black mentors or to control . Postintervention ( 11 months ) and delayed follow-up ( 24 months ) evaluations were conducted . Longitudinal analyses used multilevel models with r and om intercepts and generalized estimating equations , controlling for baseline age/gender . Stratified analyses examined baseline BMI category . RESULTS : Retention was 76 % over 2 years ; overweight/obese status declined 5 % among intervention adolescents and increased 11 % among control adolescents . Among overweight/obese youth , the intervention reduced total percentage of body fat and fat mass and increased fat-free mass at delayed follow-up and increased play-equivalent physical activity at postintervention but not at delayed follow-up . Intervention adolescents declined significantly more in snack/dessert consumption than control adolescents at both follow-up evaluations . CONCLUSIONS : At postintervention , there were intervention effects on diet and PA but not BMI category or body composition . At delayed follow-up , dietary changes were sustained and the intervention prevented an increase in BMI category . Body composition was improved for overweight/obese youth . Changes in body composition follow changes in diet and PA and may not be detected immediately after intervention PURPOSE This pilot study compares the effectiveness of home- and community-based physical activity interventions that target mothers and daughters to increase physical activity and improve health-related fitness . METHODS Mothers ( 45.18 + /- 7.49 yr ) and daughters ( 15.41 + /- 1.33 yr ) were r and omly assigned to a community-based ( CB ) ( N = 20 participants ) or home-based ( HB ) ( N = 14 participants ) program . CB participants attended three instructor-led sessions per week for 12 wk . HB participants were asked to participate in 3 sessions per week for 12 wk in a program similar to the CB program . The main difference between the programs was that CB activities were completed at a fitness facility within a university and HB activities were completed in or near the home . Before and after the intervention , changes in health-related fitness and physical activity were assessed . A series of 2 ( group assignment ) x 2 ( time ) ANOVAs were conducted to assess changes separately for mothers and daughters . RESULTS CB participants attended 77 % of the sessions , and none of the pairs dropped out . HB participants completed 70 % of the recommended sessions , and three pairs dropped out . Mothers and daughters in both groups significantly increased their participation in aerobic , muscular strength , and flexibility activities ( P = 0.02 to 0.000 ) . Daughters in both groups significantly improved their muscular endurance ( sit-ups , P = 0.000 ) . Mothers in both groups improved their muscular strength ( push-ups , P = 0.003 ) , muscular endurance ( sit-ups , P = 0.000 ) , flexibility ( sit- and -reach , P = 0.008 ) , and aerobic capacity ( 1-mile walk , P = 0.002 ) . Positive changes in diastolic blood pressure also occurred ( P = 0.008 ) . CONCLUSION Mothers and daughters responded positively to CB and HB physical activity programs . Home-based physical activity programming is a cost-effective means to increase physical activity and improve health-related fitness in these groups OBJECTIVE The present study attempts to develop and pilot the feasibility and efficacy of a novel intervention using affective messages as a strategy to increase physical activity ( PA ) levels in adolescents . Design An exploratory pilot r and omized control trial was used to compare behaviour change over 2 weeks . A modified form of the International Physical Activity Question naire was used to assess PA behaviour . A total of 120 adolescents ( 16 - 19 years ) from 4 sixth forms in West Yorkshire completed the field-based study . METHOD Participants were r and omly assigned to one of three experimental conditions , or the control condition ( N=28 ) . Participants in experimental conditions received 1 short messaging service ( SMS ) text message per day over the 2 weeks , which included manipulations of either affective beliefs ( enjoyable/unenjoyable ; N=31 ) , instrumental beliefs ( beneficial/harmful ; N=30 ) , or a combination of these ( N=31 ) . Control participants received one SMS text message per week . Outcomes were measured at baseline and at the end of the 2 week intervention . RESULTS PA levels increased by the equivalent of 31.5 minutes of moderate ( four metabolic equivalent ) activity per week during the study . Main effects of condition ( p=.049 ) , and current physical activity level ( p=.002 ) were identified , along with a significant interaction between condition and current activity level ( p=.006 ) . However , when the sample was split at baseline into active and inactive participants , a main effect of condition remained for inactive participants only ( p=.001 ) . Post hoc analysis revealed that inactive participants who received messages targeting affective beliefs increased their activity levels significantly more than the instrumental ( p=.012 ) , combined ( p=.002 ) , and control groups ( p=.018 ) . CONCLUSION Strategies based on affective associations may be more effective for increasing PA levels in inactive individuals The rising tide of obesity erodes the health of youths and many times results in adult obesity . The purpose of this investigation was to examine the effectiveness of an eight-session health promotion/transtheoretical model Internet/video-delivered intervention to increase physical activity and reduce dietary fat among low-income , culturally diverse , seventh- grade students . Those who completed more than half the sessions increased exercise , t ( 103 ) = -1.99 , p = .05 , and decreased the percentage of dietary fat , t ( 87 ) = 2.73 , p = .008 . Responses to the intervention by stage of change , race , and income are examined Aims : In this paper we evaluate the sustainability of changes of involvement in physical activity . The paper examines the effectiveness of a model aim ing at influencing the frequency of leisuretime physical activity , physical fitness and body constituency in youth . Methods : The baseline of this study was a r and omly selected sample of 13 year olds who participated in an intervention programme carried out in three schools in Poznan in 2005—08 . From a total of 199 adolescent boys a sub sample of 38 individuals from the experimental group and 34 from the control group were followed for 15 months after the interventional programme finished . From 170 girls , a sub sample of 33 from the experimental group and 32 girls from the control group were also r and omly selected for the follow-up study . Among the variables monitored were : physical fitness , body constituency , and frequency of leisuretime physical activity . All the variables were monitored in pre-test , post-test and follow-up examinations . Results : It was established that 15 months after the end of the interventional programme boys and girls from the intervention groups maintained a higher level of leisuretime physical activity than their control group peers , and similarly in the case of selected health-related components of physical fitness . No distinctive differences were found in the case of body constituency , though , apart from muscle mass and the sum of skinfolds in girls . Conclusions : The study exposed an increase in leisuretime physical activity in time and a positive influence on selected components of health-related variables . The findings confirm the effectiveness of a multi-level intervention programme involving self-determined out-of-school physical activity planning for school-age youths , indicating the importance of personal and social context The purpose of this study was to determine the feasibility , acceptability , and potential efficacy of a school-based physical activity program delivered during school sport time among adolescent girls from low income predominately linguistically diverse background s in New South Wales , Australia . Using a 3-month , 2-arm , parallel-group pilot RCT design , 38 adolescent girls ( Year 11 ) were recruited to participate in the program and r and omised into intervention ( n=17 ) or control groups ( n=21 ) . The intervention program aim ed to increase physical activity by improving enjoyment , physical self-perception and perceived competence . Baseline and follow-up ( 12 weeks ) assessment s included enjoyment of physical activity , physical self-perception , and objective ly measured physical activity during school sport sessions . Process data were collected through observations of lessons , attendance records , and interviews with participants and staff . Recruitment ( 63 % ) and retention ( 68 % ) goals were less than anticipated but similar to other studies . Participation was higher for the intervention ( 72 % ) than the control ( 60 % ) group and the intervention group reported high levels of satisfaction with the program . At follow-up , girls in the intervention group , compared with the control group , showed greater improvement in their enjoyment of physical activity during school sport ( adjusted mean difference=3.8 , 95 % Confidence Interval [ CI ] -2.4 , 10.1 ; Cohen 's d=0.42 st and ard deviation units ) and body image ( adjusted difference mean=1.0 , 95 % CI -0.4 , 2.3 ; d=0.50 ) . There was a smaller decline in participation in physical activity during school sport ( adjusted mean=13.6 , 95 % CI -21.8 , 48.9 ; d=0.24 ) . This study highlights major barriers confronting adolescent girls ' participation in school sport . Some of these include teacher attitudes and support , activities and programming , purpose and distinction , and student input . Negotiating these barriers and overcoming them in a school setting appears feasible with support from the entire school community Based on self-determination theory , the present study developed and evaluated the utility a school-based intervention to change pupils ’ physical activity intentions and self-reported leisure-time physical activity behaviour . The study evaluated utility of the intervention to promote physical activity participation over a 5-week interval of time . A cluster r and omised design targeting 215 pupils from 10 schools with schools as the unit of r and omisation was adopted ( Male = 106 , Female = 109 , Age = 14.84 , SD = 0.48 ) . Results indicated that pupils who were taught by autonomy-supportive teachers reported stronger intentions to exercise during leisure time and participated more frequently in leisure-time physical activities than pupils in the control condition . Autonomous motivation and intentions mediated the effects of the intervention on self-reported physical activity behaviour . It is concluded that self-determination theory provides a useful framework for the development of school-based interventions that ultimately affect leisure-time physical activity participation Targeting multiple behaviors for change may provide significant health benefits . This study compared interventions targeting physical activity and nutrition ( PAN ) concurrently versus physical activity ( PA ) alone . Adolescents ( N=138 ) were r and omized to the PAN or PA intervention or control condition ( n=46 per group ) . Primary outcomes were change in PA accelerometer and 3-day dietary recording from baseline to 3-month follow-up . The PAN and PA interventions were efficacious in supporting boys ' ( p<.001 ) but not girls ' ( p=.663 ) PA relative to the control condition . Dietary change was minimal . Although the findings do not reveal a decrement to PA promotion when a nutrition intervention was added , neither do they reveal any additional benefit . More studies comparing single versus multibehavioral interventions are needed Abstract The purpose of this study was to evaluate the impact of an extra-curricular school sport programme to promote physical activity among adolescents . One hundred and sixteen students ( mean age 14.2 years , s = 0.5 ) were assigned to an intervention ( n = 50 ) or comparison group ( n = 66 ) . The 8-week intervention involved structured exercise activities and information sessions . Four days of pedometer monitoring and time spent in non-organized physical activity and sedentary behaviours were measured at baseline and post-test . At baseline , participants were classified using steps per day as low-active ( girls < 11,000 , boys < 13,000 ) or active ( girls ≥ 11,000 , boys ≥ 13,000 ) and the effects of the intervention were assessed using these subgroups . Adolescents in the intervention group classified as low-active at baseline increased their step counts across the 8-week intervention ( baseline : 7716 steps/day , s = 1751 ; post-test : 10,301 steps/day , s = 4410 ; P < 0.05 ) and accumulated significantly more steps ( P < 0.05 ) than their peers in the comparison group ( baseline : 8414 steps/day , s = 2460 ; post-test : 8248 steps/day , s = 3674 ; P = 0.879 ) . The results of the present study provide further evidence that physical activity monitoring using pedometers is an effective strategy for increasing activity among low-active adolescents OBJECTIVE Many adolescents do not meet national guidelines for participation in regular moderate or vigorous physical activity ( PA ) ; limitations on sedentary behaviors ; or dietary intake of fruits and vegetables , fiber , or total dietary fat . This study evaluated a health care-based intervention to improve these behaviors . DESIGN R and omized controlled trial . SETTING Primary care with follow-up at home . PARTICIPANTS Eight hundred seventy-eight adolescent girls and boys aged 11 to 15 years . INTERVENTIONS Two experimental conditions : ( 1 ) Primary care , office-based , computer-assisted diet and PA assessment and stage-based goal setting followed by brief health care provider counseling and 12 months of monthly mail and telephone counseling and ( 2 ) a comparison condition addressing sun exposure protection . MAIN OUTCOME MEASURES Minutes per week of moderate plus vigorous PA measured by self-report and accelerometer ; self-report of days per week of PA and sedentary behaviors ; and percentage of energy from fat and servings per day of fruits and vegetables measured by three 24-hour diet recalls . Body mass index ( calculated as weight in kilograms divided by the square of height in meters ) was a secondary outcome . RESULTS Compared with adolescents in the sun protection condition , girls and boys in the diet and PA intervention significantly reduced sedentary behaviors ( intervention vs control change , 4.3 to 3.4 h/d vs 4.2 to 4.4 h/d for girls , respectively [ P = .001 ] ; 4.2 to 3.2 h/d vs 4.2 to 4.3 h/d for boys , respectively [ P = .001 ] ) . Boys reported more active days per week ( intervention vs control change : 4.1 to 4.4 d/wk vs 3.8 to 3.8 d/w , respectively [ P = .01 ] ) , and the number of servings of fruits and vegetables for girls approached significance ( intervention vs control change , 3.5 to 4.2 servings/d vs 3.5 to 3.9 servings/d , respectively [ P = .07 ] ) . No intervention effects were seen with percentage of calories from fat or minutes of PA per week . Percentage of adolescents meeting recommended health guidelines was significantly improved for girls for consumption of saturated fat ( intervention vs control change , 23.4 % to 41.0 % vs 18.5 % to 31 % , respectively [ relative risk , 1.33 ; 95 % confidence interval , 1.01 - 1.68 ] ) and for boys ' participation in d/wk of PA ( intervention vs control change , 45.3 % to 55.4 % vs 41.9 % to 38.0 % , respectively [ relative risk , 1.47 ; 95 % confidence interval , 1.19 - 1.75 ] ) . No between-group differences were seen in body mass index . CONCLUSIONS Improvements in some diet , PA , and sedentary behaviors in adolescents can be enabled through the use of a 1-year , integrated intervention using the computer , health provider counseling , mail , and telephone . The amount of intervention received may contribute to its efficacy The Healthy Youth Places ( HYP ) intervention targeted increased fruit and vegetable consumption ( FV ) and physical activity ( PA ) through building the environmental change skills and efficacy of adults and youth . HYP included group training for adult school site leaders , environmental change skill curriculum , and youth-led FV and PA environment change teams . Sixteen schools were r and omized to either implement the HYP program or not . Participants ( N = 1,582 ) were assessed on FV and PA and hypothesized HYP program mediators ( e.g. , proxy efficacy ) at the end of sixth grade ( baseline ) , seventh grade ( Postintervention Year 1 ) , and eighth grade ( Postintervention Year 2 ) . After intervention , HYP schools did not change in FV but did significantly change in PA compared to control schools . Proxy efficacy to influence school PA environments mediated the program effects . Building the skills and efficacy of adults and youth to lead school environmental change may be an effective method to promote youth PA BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness Purpose . To determine whether the amount of television ( TV ) watched by participants enrolled in a physical activity intervention mediates or moderates program effectiveness . Design . Nine-month , controlled , school-based physical activity intervention . Setting . Public high school . Participants . One hundred twenty-two sedentary adolescent females ( mean + st and ard deviation age = 15.04 + 0.79 years ) . Intervention . Supervised in-class exercise , health education , and internet-based self-monitoring . Measures . Physical activity by 3-day physical activity recall ; TV viewing by self-reports ; cardiovascular fitness by cycle ergometer . Analysis . T-tests were conducted to examine between-group differences . Linear regression equations tested the mediating or moderating role of TV watching relative to the intervention . Results . TV viewing moderated the intervention 's effect on vigorous activity ; the intervention significantly predicted change in physical activity among high ( β = −.45 ; p < .001 ) , but not among low ( p > .05 ) , TV watchers . TV viewing did not mediate the intervention effect . Conclusions . Consistent with displacement theory , adolescents who watched more TV prior to the intervention showed postintervention increases in vigorous physical activity and concomitant decreases in TV viewing , whereas those who watched less TV showed no change in physical activity or TV viewing PURPOSE To investigate the effect of a six-month teacher-led osteogenic physical activity program , vs. a self-led activity program , on ultrasound measurements of bone in inactive teenage girls . METHODS Ninety sedentary girls [ mean ( SD ) age 16.3 ( .6 ) years ] were identified from 300 assessed for physical activity across five schools in southeast Irel and . Schools were matched and r and omly assigned to a teacher-led physical activity ( TLPA ) program , a self-led physical activity ( SLPA ) program , or a control group . Broadb and ultrasound attenuation ( BUA ) , speed of sound ( SOS ) , and os calcis stiffness index ( OCSI ) were measured using a portable ultrasound machine . Anthropometry , aerobic fitness , calcium intake , and physical activity were assessed , and focus groups held one month after program completion . Descriptive statistics , paired t-tests , and analysis of variance were used to analyze the data . RESULTS Both intervention groups demonstrated significant improvements ( p < .05 ) in BUA , SOS , OCSI and aerobic fitness , i.e. , TLPA : + 14.9 % , + 21.9 % , + 15.9 % , and + 8.5 % , respectively , and SLPA : + 10.6 % , + 30.3 % , + 15.6 % , and + 5.1 % , respectively , with no change in controls . Differences between intervention groups and controls were significant for BUA and OCSI ( p < .05 ) . TLPA and SLPA groups engaged in an average of 4.5 and 3.4 hours/week of physical activity , respectively , over the intervention period . The SLPA group continued to exercise after the intervention had ceased , whereas the TLPA group did not . CONCLUSIONS Previously inactive teenage girls can adhere to an osteogenic activity program whether supervised or directing their own activity . Longer-term , sustainable initiatives with this age group are needed and might focus on developing personal skills for physical activity BACKGROUND This study examines whether the adolescents ' current levels of physical activity are increased by their physicians ' advice provided in the office , in accordance with the American Medical Association recommendation . METHODS The first adolescent ( 12 - 21 years old ) of whichever age and gender , passing through six family physicians ' offices during a 6-month period was assigned to the intervention group , and the second adolescent of the same age and gender was assigned to the control group . Each patient was classified as active , partially active , and inactive , according to how they answered the questions about their physical activity levels , and patients in the intervention group were then provided with reinforcement , increase , or initiation counseling , respectively . Identical procedures were repeated at the 6- and 12-month office visits . Changes in prevalence of activity , as well as , duration , frequency , and intensity of exercise and /or sports were verified at each visit . RESULTS Of the 87.5 % of the original sample that completed the survey , 6- and 12-month data were available for 70.1 % . Among the 392 adolescents that finished the study , those provided with counseling had 41.5 % more active adolescents , as well as 26.8 % , 38.0 % and 26.2 % higher duration , frequency and intensity , respectively , than the control group . CONCLUSIONS The proportion of active adolescents , as well as , the duration , frequency and intensity of leisure time exercise and /or sports are increased by physician advice OBJECTIVES Many adolescent girls fail to meet national guidelines for physical activity , and the prevalence of obesity is increasing among this group . Our study examined the effects of a comprehensive school-based intervention on physical activity among high-school girls . METHODS A group-r and omized controlled field trial was conducted at 24 high schools . A school-based sample of 2744 girls ( 48.7 % African American , 46.7 % White ) participated in a measurement protocol when they were in eighth and then ninth grade . A comprehensive physical activity intervention was design ed to change the instructional program and the school environment to increase support for physical activity among girls . RESULTS At follow-up , 45 % of girls in the intervention schools and 36 % of girls in the control schools reported vigorous physical activity during an average of 1 or more 30-minute time blocks per day over a 3-day period . CONCLUSIONS A comprehensive school-based intervention can increase regular participation in vigorous physical activity among high-school girls BACKGROUND This study reports the results of a 9-week intervention on the physical activity levels of adolescent males . METHODS Participants were 473 10- to 14-year-old Houston Boy Scouts ( 42 troops ) with troops r and omly assigned to intervention or control conditions . Data were collected in spring ( 16 troops ) and fall ( 26 troop ) waves during 2003 . Intervention participants received a 9-week troop and Internet program to increase physical activity skills , self-efficacy and goal - setting . Physical activity was assessed at baseline , end of the intervention ( Post#1 ) and post-6 months ( Post#2 ) by accelerometer . Minutes of sedentary , light and moderate to vigorous physical activity were calculated . Repeated measure analyses were performed to test differences in physical activity over time between groups with participants nested in troops . RESULTS A three-way interaction ( group * time * wave ) that approached significance ( P = 0.051 ) indicated a 12-min reduction in sedentary behavior among spring intervention participants . A significant three-way interaction ( P = 0.011 ) ( group * time * wave ) indicated a 12-min increase in light intensity activity among the spring intervention group . CONCLUSION Participation in the Fit for Life badge program result ed in a trend towards a small decrease in sedentary behavior and increased light intensity physical activity among spring participants only . There was no effect on moderate to vigorous physical activity The aim of the present study was to evaluate the effects of a middle school physical activity and healthy eating intervention , including an environmental and computer-tailored component , and to investigate the effects of parental involvement . A r and om sample of 15 schools with seventh and eight grade rs was r and omly assigned to one of three conditions : ( i ) intervention with parental involvement , ( ii ) intervention alone and ( iii ) control group . In 10 schools , an intervention , combining environmental changes with computer-tailored feedback , was implemented over 2 school years . In five intervention schools , increased parental support was added . Physical activity was measured with question naires in the total sample and with accelerometers in a sub- sample of children . Fat intake , fruit , water and soft drink consumption were measured using food-frequency question naires . Results showed significant positive intervention effects on physical activity in both genders and on fat intake in girls . Parental involvement did not increase intervention effects . It can be concluded that physical activity and eating behaviours of middle school children can be improved by school-based strategies combining environmental and personal interventions . The use of personalized computer-tailored interventions seems to be a promising tool for targeting adolescents but needs to be further explored BACKGROUND Weight-related problems are prevalent in adolescent girls . PURPOSE To evaluate New Moves , a school-based program aim ed at preventing weight-related problems in adolescent girls . DESIGN School-based group-r and omized controlled design . SETTING / PARTICIPANTS 356 girls ( mean age=15.8±1.2 years ) from six intervention and six control high schools . More than 75 % of the girls were racial/ethnic minorities and 46 % were overweight or obese . Data were collected in 2007 - 2009 and analyzed in 2009 - 2010 . INTERVENTION An all-girls physical education class , supplemented with nutrition and self-empowerment components , individual sessions using motivational interviewing , lunch meetings , and parent outreach . MAIN OUTCOME MEASURES Percentage body fat , BMI , physical activity , sedentary activity , dietary intake , eating patterns , unhealthy weight control behaviors , and body/self-image . RESULTS New Moves did not lead to significant changes in the girls ' percentage body fat or BMI but improvements were seen for sedentary activity , eating patterns , unhealthy weight control behaviors , and body/self-image . For example , in comparison to control girls , at 9-month follow-up , intervention girls decreased their sedentary behaviors by approximately one 30-minute block a day ( p=0.050 ) ; girls increased their portion control behaviors ( p=0.014 ) ; the percentage of girls using unhealthy weight control behaviors decreased by 13.7 % ( p=0.021 ) ; and improvements were seen in body image ( p=0.045 ) and self-worth ( p=0.031 ) . Additionally , intervention girls reported more support by friends , teachers , and families for healthy eating and physical activity . CONCLUSIONS New Moves provides a model for addressing the broad spectrum of weight-related problems among adolescent girls . Further work is needed to enhance the effectiveness of interventions to improve weight status of youth OBJECTIVE To investigate the differences in effects of a computer tailored physical activity advice as compared to generic information in adolescents . METHODS Students ( mean age , 14.6+/-1.2 ) out of 90 classes from six different Flemish schools were r and omly assigned to the tailored intervention ( n=563 ) or the generic non-tailored intervention ( n=608 ) condition . Both interventions included information on public health recommendations and tips on becoming more active . Participants in both groups received their assessment and feedback at baseline , at 4 weeks and at 3 months during school hours . Physical activity levels were determined using an adolescent adaptation of the International Physical Activity Question naire ( IPAQ ) . RESULTS After 4 weeks , almost all physical activity scores increased over time in both the generic and the tailored intervention group . No differences between groups were found ( all F < or = 0.07 ) . After 3 months , the generic intervention was more effective for increasing ' walking in leisure time ' among students not complying with recommendations . For all other physical activity scores , no differences between groups were found ( all F < or = 2.3 ) . CONCLUSIONS In contrast to the expectations , changes in physical activity scores did not differ between the tailored and the non-tailored intervention group . For most of the physical activity scores increases were found in both groups |
2,131 | 22,418,776 | Conclusion This meta- analysis of cohort studies does not support an independent association between diets high in carbohydrate , glycemic index , or glycemic load and colorectal cancer risk | Background Dietary carbohydrate , glycemic index , and glycemic load are thought to influence colorectal cancer risk through hyperinsulinemia .
We review and quantitatively summarize in a meta- analysis the evidence from prospect i ve cohort studies . | Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive . Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels . The effect of consuming a high glycemic diet on colorectal risk , however , remains uncertain . Two prospect i ve cohort studies , the Nurses ' Health Study and the Health Professionals Follow-up Study , contributed up to 20 years of follow-up . After exclusions , 1,809 incident colorectal cancers were available for analyses . Dietary glycemic load ( GL ) was calculated as a function of glycemic index ( postpr and ial blood glucose response as compared with a reference food ) , carbohydrate content , and frequency of intake of individual foods reported on food frequency question naires . Multivariable Cox proportional hazards models were used to adjust for potential confounders . Intakes of dietary carbohydrate , GL , overall glycemic index , sucrose , and fructose were not associated with colorectal cancer risk in women . A small increase in risk was observed in men with high dietary GL ( multivariate relative risk , 1.32 ; 95 % confidence interval , 0.98 - 1.79 ; highest versus lowest quintile ) , sucrose or fructose ( multivariate relative risk , 1.37 ; 95 % confidence interval , 1.05 - 1.78 ; highest versus lowest quintile of fructose , P = 0.008 ) . Associations were slightly stronger among men with elevated body mass index ( > or = 25 kg/m(2 ) ) . Results among women were similar after stratifying by body mass index or physical activity . High intakes of GL , fructose , and sucrose were related to an elevated colorectal cancer risk among men . For women , however , these factors did not seem to increase the risk of colorectal cancer The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content To investigate the relation of dietary intakes of sucrose , meat , and fat , and anthropometric , lifestyle , hormonal , and reproductive factors to colon cancer incidence , data were analyzed from a prospect i ve cohort study of 35,215 Iowa ( United States ) women , aged 55–69 years and without a history of cancer , who completed mailed dietary and other question naires in 1986 . Through 1990 , 212 incident cases of colon cancer were documented . Proportional hazards regression was used to adjust for age and other risk factors . Risk factors found to be associated significantly with colon cancer included : ( i ) sucrose-containing foods and beverages other than ice cream/milk ; relative risks ( RR ) across the quintiles=1.00 , 1.73 , 1.56 , 1.54 , and 2.00 ( 95 % confidence intervals [ CI ] for quintiles two and five exclude 1.0 ) ; ( ii ) sucrose ; RR across the quintiles=1.00 , 1.70 , 1.81 , 1.82 , and 1.45 ( CI for quintiles two through four exclude 1.0 ) ; ( iii ) height ; RR=1.23 for highest to lowest quintile ( P for trend-0.02 ) ; ( iv ) body mass index ; RR=1.41 for highest to lowest quintile ( P for trend=0.03 ) ; and ( v ) number of livebirths , RR=1.59 for having had one to two livebirths and 1.80 for having had three or more livebirths compared with having had none ( P for trend=0.04 ) . These data support hypotheses that sucrose intake or being tall or obese increases colon cancer risk ; run contrary to the hypothesis that increased parity decreases risk ; support previous findings of no association with demographic factors other than age , cigarette smoking , or use of oral contraceptives or estrogen replacement therapy ; and raise questions regarding previous associations with meat , fat , protein , and physical activity . Cancer Causes and Control 1994 , 5 , 38–52 Although diet is believed to influence colorectal cancer risk , the long-term effects of a diet with a high glycemic load are unclear . The growing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggests that a diet inducing high blood glucose levels and an elevated insulin response may contribute to a metabolic environment conducive to tumor growth . We prospect ively followed a cohort of 38 451 women for an average of 7.9 years and identified 174 with incident colorectal cancer . We used baseline dietary intake measurements , assessed with a semiquantitative food-frequency question naire , to examine the associations of dietary glycemic load , overall dietary glycemic index , carbohydrate , fiber , nonfiber carbohydrate , sucrose , and fructose with the subsequent development of colorectal cancer . Cox proportional hazards models were used to estimate relative risks ( RRs ) . Dietary glycemic load was statistically significantly associated with an increased risk of colorectal cancer ( adjusted RR = 2.85 , 95 % confidence interval [ CI ] = 1.40 to 5.80 , comparing extreme quintiles of dietary glycemic load ; P(trend ) = .004 ) and was associated , although not statistically significantly , with overall glycemic index ( corresponding RR = 1.71 , 95 % CI = 0.98 to 2.98 ; P(trend ) = .04 ) . Total carbohydrate ( adjusted RR = 2.41 , 95 % CI = 1.10 to 5.27 , comparing extreme quintiles of carbohydrate ; P(trend ) = .02 ) , nonfiber carbohydrate ( corresponding RR = 2.60 , 95 % CI = 1.22 to 5.54 ; P(trend ) = .02 ) , and fructose ( corresponding RR = 2.09 , 95 % CI = 1.13 to 3.87 ; P(trend ) = .08 ) were also statistically significantly associated with increased risk . Thus , our data indicate that a diet with a high dietary glycemic load may increase the risk of colorectal cancer in women The relation between diet and female colorectal cancer was analyzed in a prospect i ve study of 14,727 women aged 34 - 65 years , who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991 . They were followed through the end of 1994 ( average 7.1 yrs ) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries , result ing in 100 incident cases of colorectal cancer . There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories , total or subclasses of fat , carbohydrate , or dietary fiber , whereas there was an inverse association with total protein . Among major food groups , there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish ( relative risk for 4th vs. 1st quartile = 0.49 , 95 % confidence interval = 0.27 - 0.89 ) . A similar inverse association was also observed for consumption of dairy products , and this association was explained mainly by calcium , not by other nutrients , such as fat or protein . The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer , whereas the relations with red meat or total fat remained unclear Diet has long been thought to be an important factor in the etiology of colorectal cancer . The specific dietary nutrients or factors responsible for this disease , the second leading cause of cancer death in the United States [ 1 ] , have not , however , been clearly eluci date d. Colorectal adenomatous polyps ( here referred to as polyps ) are generally considered to be precursor lesions for most cases of colorectal carcinoma [ 2 - 4 ] ; however , little is known about their risk factors . Since the introduction of fiberoptic endoscopy , especially colonoscopy , attention has focused on the potential for preventing colorectal cancer by screening for and resecting the adenomas [ 5 , 6 ] . Because of their high recurrence rate after resection [ 7 , 8 ] , these polyps have been used as an end point for the study of potential chemopreventive agents . Four studies have explored potential dietary risk factors for incident colorectal adenomatous polyps [ 9 - 12 ] . No previous observational studies have explored the role of diet or other lifestyle factors in the recurrence of polyps after polypectomy . We discuss the results of a casecontrol study of colorectal polyps among patients from three colonoscopy practice s and analyze dietary risk factors for both incident and recurrent polyps . Methods Our study sample included patients having colonoscopy at three colonoscopy practice s in New York City between April 1986 and March 1988 . In total , 2988 patients were evaluated . Of these , 2443 ( 81.8 % ) were eligible for our study ( patients had to be between 35 and 84 years of age ; reside in New York , New Jersey , or Connecticut ; speak English or Spanish ; and have colonoscopy to at least the splenic flexure ) . The colonoscopists completed data sheets indicating the reason for colonoscopy and the clinical findings at the time of colonoscopy . The study pathologist review ed slides of all suspected neoplastic lesions . All eligible participants received a letter signed by their colonoscopist introducing the study . A trained interviewer then contacted and interviewed participants by telephone . Alternatively , the question naire was mailed for self-completion and was followed by a telephone interview to resolve any remaining questions . An earlier study indicated that the results obtained for dietary factors were similar for both interview methods [ 13 ] . The interview itself consisted of a general question naire that focused on demographic characteristics , medical history , lifestyle , family history , and other topics . The dietary interview consisted of the Block food frequency question naire and specified food intake for a period 3 to 5 years before the colonoscopy [ 14 ] . Ultimately , 1956 dietary question naires were completed ( 80.1 % of eligible patients ) . Of these , 71 % were conducted by telephone , and 29 % were returned by mail . An incident case of adenomatous polyps was defined as an eligible participant with no history of colon carcinoma , adenomatous polyps , or inflammatory bowel disease who was found to have one or more pathologically defined polyps on the index colonoscopy . The incident control group consisted of persons who were found to be free of colorectal neoplasia on index colonoscopy and who were without a history of adenomatous polyps , colon cancer , or inflammatory bowel disease . A case of recurrent polyps was defined as an eligible participant with a self-reported history of one or more polyps who had a pathologically confirmed polyp on the index colonoscopy . The recurrent control was defined as a participant whose index colonoscopy showed no colorectal neoplasia but who had a history of one or more polyps . Cases and controls with a history of colorectal cancer or inflammatory bowel disease were excluded . Although we did not have pathologic confirmation of all initial polyps , we did obtain pathology reports on a r and om sample of 100 recurrent cases and controls and found 97 to be adenomatous . By these criteria , 286 incident cases ( 162 men and 124 women ) and 480 incident controls ( 210 men and 270 women ) were identified , whereas 186 recurrence cases ( 130 men and 56 women ) and 330 recurrence controls ( 187 men and 143 women ) were found . Food item and nutrient data were generated by software programs provided by Block and coworkers [ 14 ] at the National Cancer Institute . The main analyses were done using logistic regression modelling and maximum likelihood ratios [ 15 ] in the BMDP-LR program . Analyses were conducted separately for men and women . Age , Quetelet index , and caloric intake were entered as covariates for most analyses . A previous study by our group had shown obesity , as measured by Quetelet index , to be a risk factor for polyps among women ; the trend for men was not significant [ 16 ] . Analyses in which nutrients were st and ardized per 1000 kilocalories were also done for comparison [ 17 ] . For each nutrient or food group , quartiles were defined by review of the control group data ; the lowest quartile was given a reference value of 1.0 , and odds ratios were calculated for each of the other quartiles , with 95 % confidence intervals ( CIs ) for the highest-to-lowest quartile comparison . The probability of a linear trend was calculated by entering the four quartiles as ordered categories . Results The case and control groups for the incidence and recurrence studies were generally similar in age distribution and education . Table 1 shows a comparison of the characteristics of the case and control groups for both the incident and recurrent groups . Most polyps were 5 mm or larger in size and had at least some degree of atypia . The site distribution of the incident polyps showed a preponderance to the left . Most incident case and control participants had colonoscopy because of overt or occult rectal bleeding . A larger proportion of the recurrent polyps were right-sided ( P = 0.005 ) . The time interval from initial polypectomy to index colonoscopy was 4.3 years for cases and 3.7 years for controls ( P > 0.2 ) . Table 1 . Polyp Characteristics for Incident and Recurrent Cases Tables 2 and 3 show the odds ratios by quartile , using the lowest quartile as the referent group , for some of the 15 nutrients and food groups evaluated . The results for vegetables , red meat , beef , cheese , protein , vitamin C , and carotene are not shown ; however , no consistent differences were found . Table 2 . Odds Ratios of Incident Polyps by Quartile of Selected Nutrients and Food Groups , Adjusted for Age , Quetelet Index , and Caloric Intake Table 3 . Odds Ratios of Recurrent Polyps by Quartile of Selected Nutrients and Food Groups , Adjusted for Age , Quetelet Index , and Caloric Intake Men The only dietary risk factor statistically associated with the risk for colorectal adenomatous polyps in men was caloric intake ; however , this association was in a direction opposite to that ordinarily expected [ 18 ] . Women In contrast , various dietary factors were observed to be associated with the risk for colorectal adenomatous polyps in women ( Tables 2 and 3 ) . Increased saturated fat , decreased fish and chicken , increased meat-to-fish and -chicken ratio , and decreased vitamin A intake increased the risk for incident polyps ( Table 2 ) . Increased caloric intake , increased total fat , increased saturated fat , and decreased fiber intake all raised the risk for recurrent polyps in women , whereas vitamin A and carbohydrate intake had borderline protective effects ( Table 3 ) . Analyses were also done using nutrient density ( nutrient compared with caloric intake ) instead of entering calories as a covariate . The results are not shown , but the same risk factors were statistically significant for incident polyps in women , although the estimated odds ratios were larger . In addition , fiber was protective for incident polyps in women ( odds ratio , 0.6 ; CI , 0.3 to 1.1 ; P = 0.06 ) . The same dietary factors were also associated with recurrent polyps in women , although the odds ratio estimates were again larger . Both vitamin A ( odds ratio , 0.5 ; CI , 0.2 to 1.1 ; P = 0.06 ) and carbohydrate intake ( odds ratio , 0.4 ; CI , 0.2 to 1.0 ; P = 0.001 ) were more clearly protective . Subgroup Analyses For each of the dietary factors associated with colorectal polyps in women , further subgroup analyses were done for right-sided polyps only , for left-sided polyps only , and for polyps 5 mm or larger in size . Generally , no major variations were observed for the various subgroups , although some reduction was seen in statistical power because of the smaller number of cases . To determine the independent effect of each of the variables found to be associated with polyps in women , we conducted further multiple logistic regression analyses using various dietary factors as covariates . The elevated risk associated with increased consumption of saturated fats remained after adjustment for fiber or vitamin A. Discussion Many studies have suggested that diet plays a role in the etiology of colorectal cancer [ 19 - 35 ] . Evidence suggests that increased consumption of saturated fat is a causal factor and that increased consumption of fiber , ( particularly fruit and vegetable fiber ) is protective [ 26 ] . Similarly , an increased risk has been associated with greater consumption of red meat compared with chicken or fish [ 19 ] , and a protective effect has been linked to consumption of vegetables [ 35 ] . A protective effect of such micronutrients as vitamin A , carotene [ 32 - 34 ] , and calcium [ 27 - 30 ] has also been suggested , although the evidence is less compelling . Because adenomatous polyps are known precursors for colorectal cancer , three casecontrol studies [ 9 - 11 ] have explored their association with diet . Despite their limitations , each study has suggested a protective effect for fiber . A recent cohort study [ 12 ] of male health professionals found saturated fat and decreased fiber , as well as increased red meat-to-fish and meat-to-chicken ratio , to be risk factors for left-sided incident polyps . A small study by our group also showed that supplemental vitamins had no influence on the development Prospect i ve epidemiologic data on the effects of different types of dietary sugars on cancer incidence have been limited . In this report , we investigated the association of total sugars , sucrose , fructose , added sugars , added sucrose and added fructose in the diet with risk of 24 malignancies . Participants ( n = 435,674 ) aged 50–71 years from the NIH‐AARP Diet and Health Study were followed for 7.2 years . The intake of individual sugars was assessed using a 124‐item food frequency question naire ( FFQ ) . Cox proportional hazards regression was used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) in multivariable models adjusted for confounding factors pertinent to individual cancers . We identified 29,099 cancer cases in men and 13,355 cases in women . In gender‐combined analyses , added sugars were positively associated with risk of esophageal adenocarcinoma ( HRQ5 vs. Q1 : 1.62 , 95 % CI : 1.07–2.45 ; ptrend = 0.01 ) , added fructose was associated with risk of small intestine cancer ( HRQ5 vs. Q1 : 2.20 , 95 % CI : 1.16–4.16 ; ptrend = 0.009 ) and all investigated sugars were associated with increased risk of pleural cancer . In women , all investigated sugars were inversely associated with ovarian cancer . We found no association between dietary sugars and risk of colorectal or any other major cancer . Measurement error in FFQ‐reported dietary sugars may have limited our ability to obtain more conclusive findings . Statistically significant associations observed for the rare cancers are of interest and warrant further investigation Mounting evidence suggests that high circulating levels of insulin might be associated with increased colorectal cancer risk . The glycemic effects of diets high in refined starch may increase colorectal cancer risk by affecting insulin and /or insulin-like growth factor-I levels . We examined the association between dietary intake and colorectal cancer risk in a cohort of 49 124 women participating in a r and omized , controlled trial of screening for breast cancer in Canada . Linkages to Canadian mortality and cancer data bases yielded data on mortality and cancer incidence up to December 31 , 2000 . During an average 16.5 years of follow-up , we observed 616 incident cases of colorectal cancer ( 436 colon cancers , 180 rectal cancers ) . Rate ratios for colorectal cancer for the highest versus the lowest quintile level were 1.05 ( 95 % confidence interval [ CI ] = 0.73 to 1.53 ; P(trend ) = .94 ) for glycemic load , 1.01 ( 95 % CI = 0.68 to 1.51 ; P(trend ) = .66 ) for total carbohydrates , and 1.03 ( 95 % CI = 0.73 to 1.44 ; P(trend ) = .71 ) for total sugar . Our data do not support the hypothesis that diets high in glycemic load , carbohydrates , or sugar increase colorectal cancer risk Diets with a high glycemic index and glycemic load have been hypothesized to be implicated in the etiology of colorectal cancer owing to their potential to increase postpr and ial glucose and insulin levels . Prospect i ve data on glycemic index and glycemic load in relation to colorectal cancer risk are limited and inconsistent . Therefore , the authors prospect ively investigated the associations of dietary carbohydrate , glycemic index , and glycemic load with the incidence of colorectal cancer among 61,433 Swedish women who were free of cancer in 1987 - 1990 and completed a 67-item food frequency question naire . During follow-up through June 2005 , 870 incident cases of colorectal adenocarcinoma were diagnosed . Carbohydrate intake , glycemic index , and glycemic load were not associated with risk of colorectal cancer , colon cancer , or rectal cancer . The multivariate hazard ratios for colorectal cancer comparing the highest with the lowest quintile were 1.10 ( 95 % confidence interval : 0.85 , 1.44 ) for carbohydrate intake , 1.00 ( 95 % confidence interval : 0.75 , 1.33 ) for glycemic index , and 1.06 ( 95 % confidence interval : 0.81 , 1.39 ) for glycemic load . Results did not vary by body mass index . The findings from this prospect i ve study do not support the hypothesis that a high carbohydrate intake , a high glycemic index , and a high glycemic load increase the risk of colorectal cancer Background There is considerable support for associations between insulin and IGF-I levels and colorectal cancer . Diet may relate to colorectal cancer through this mechanism , for example , diets high in glycemic index , glycemic load and /or carbohydrate are hypothesized to increase insulin load and the risk of insulin resistance , hyperinsulinemia . Case – control studies support this hypothesis , but prospect i ve cohorts have had mixed results . Methods In the Breast Cancer Detection Demonstration Project ( BCDDP ) follow-up cohort of 45,561 women , we used Cox proportional hazards regression to assess the distribution of 490 incident cases of colorectal cancer ascertained during 8.5 years of follow-up across quintiles of carbohydrate intake , glycemic index , and glycemic load . We also stratified by combined BMI and physical activity levels . Results We found reductions in colorectal cancer risk for diets high in carbohydrate ( RR for Q5 vs. Q1 = 0.70 , 95 % CI : 0.50–0.97 ) and glycemic index ( 0.75 , 95 % CI : 0.56–1.00 ) , and no significant association for glycemic load ( 0.91 , 95 % CI : 0.70–1.20 ) . Inverse associations were weakest in normal weight active persons . The inverse association for glycemic index was strongest for the portion from dairy food . Conclusions These results do not support an association between diets high in carbohydrate , glycemic index or glycemic load and colorectal cancer Western style diets and lifestyles are associated with increasing rates of obesity , diabetes and insulin resistance . Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF‐I and decreasing the bioactivity of some of its binding proteins . The objective of this study was to determine the association of increasing levels of serum C‐peptide , a biomarker of pancreatic insulin secretion , and IGF binding proteins ( IGFBP ) ‐1 and ‐2 with colorectal cancer risk in a case – control study nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) , a large cohort involving 10 Western European countries . A total of 1,078 colorectal cancer cases were matched ( age , date of blood donation , fasting status , gender , study center ) to an equal number of control subjects . Relative cancer risks were estimated using conditional logistic regression models . Serum C‐peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile ( OR = 1.56 , 95 % CI = 1.16–2.09 , ptrend < 0.01 ) , which was slightly attenuated after adjustment for BMI and physical activity ( OR = 1.37 , 95 % CI = 1.00–1.88 , ptrend = 0.10 ) . When stratified by anatomical site , the cancer risk was stronger in the colon ( OR = 1.67 , 95 % CI = 1.14–2.46 , ptrend < 0.01 ) than in the rectum ( OR = 1.42 , 95 % CI = 0.90–2.25 , ptrend = 0.35 ) . The cancer risk estimates were not heterogeneous by gender or fasting status . No clear colorectal cancer risk associations were observed for IGFBP‐1 or ‐2 . This large prospect i ve study confirms that hyperinsulinemia , as determined by C‐peptide levels , is associated with an increased colorectal cancer risk . © 2007 Wiley‐Liss , Background : Circulating insulin levels have been positively associated with risk of colorectal cancer ; however , it remains unclear whether a diet inducing an elevated insulin response influences colorectal cancer risk . On the basis of a novel insulin index for individual foods , we estimated insulin dem and for overall diets and assessed its association with colorectal cancer in the Nurses ' Health Study and Health Professionals Follow-up Study . Methods : We followed 86,740 women and 46,146 men who were free of cancer and diabetes at baseline and identified a total of 2,481 colorectal cancer cases during up to 26 years of follow-up . Dietary insulin load was calculated as a function of food insulin index and the energy content of individual foods was reported on food frequency question naires . Average dietary insulin index was calculated by dividing the dietary insulin load by the total energy intake . Results : Dietary insulin load and dietary insulin index were not associated with risk of colorectal cancer . Comparing the highest with the lowest quintiles , the pooled multivariate relative risks of colorectal cancer were 0.91 ( 95 % CI = 0.79–1.05 ) for dietary insulin load and 0.93 ( 95 % CI = 0.81–1.08 ) for dietary insulin index . Body mass index and physical activity did not modify the association of dietary insulin load or index with colorectal cancer . Conclusion : A diet high in foods that increase postpr and ial insulin levels did not increase the risk of colorectal cancer in this large prospect i ve study . Impact : This study is the first to investigate insulin index and load in relation to colorectal cancer . Cancer Epidemiol Biomarkers Prev ; 19(12 ) ; 3020–6 . © 2010 AACR Mortality rates from colon cancer in the USA are highest in population s exposed to the least amounts of natural sunlight ; differences in endogenous vitamin D production and calcium absorption could be responsible . To investigate this possibility , the association of dietary vitamin D and calcium with 19-year risk of colorectal cancer was examined in 1954 men who had completed detailed , 28-day dietary histories in the period 1957 - 59 . Risk of colorectal cancer was inversely correlated with dietary vitamin D and calcium . In the quartiles of a combined index of dietary vitamin D and calcium , from lowest to highest , observed risks of colorectal cancer were 38.9 , 24.5 , 22.5 , and 14.3/1000 population . This association remained significant after adjustment for age , daily cigarette consumption , body mass index , ethanol consumption , and percentage of calories obtained from fat BACKGROUND Mixed results have been reported in recent epidemiologic studies in Western population s that have investigated the hypothesis that high glycemic load may increase the risk of colorectal cancer . This association has not been prospect ively evaluated in other population s. OBJECTIVE We examined the association of overall glycemic index and glycemic load with colorectal cancer risk in a prospect i ve cohort of Chinese women . DESIGN A total of 73,061 women aged 40 - 70 y and free of cancer at enrollment were included in this analysis . Usual dietary intake was assessed at baseline ( 1997 - 2000 ) and reassessed during the first follow-up ( 2000 - 2002 ) through in-person interviews by using a vali date d food-frequency question naire . RESULTS During an average follow-up of 9.1 y , 475 incident colorectal cancer cases were identified . Glycemic load was not associated with colorectal cancer risk ( P for trend = 0.84 ) . The multivariable hazard ratio for the highest compared with the lowest quintile of glycemic load was 0.94 ( 95 % CI : 0.71 , 1.24 ) . Similar results were also observed for associations with dietary glycemic index and total carbohydrate intake , and results did not vary by excluding individuals with a history of diabetes from the analysis . CONCLUSION This prospect i ve study , conducted in a population with a high intake of carbohydrates , provides no evidence that a high-glycemic index diet or high glycemic load is associated with an increased risk of colorectal cancer |
2,132 | 28,663,934 | SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes , likely result ing from a mixture of an initial reduction of eGFR and long-term renal function preservation .
SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD | AIM To evaluate the effects of sodium-glucose co-transporter 2 ( SGLT2 ) inhibition on renal function and albuminuria in patients with type 2 diabetes . | Patients with type 2 diabetes mellitus ( T2DM ) with a glycated haemoglobin ( HbA1c ) level ≥7 and ≤10 % were r and omized to receive empagliflozin 12.5 mg twice daily ( n = 219 ) , 25 mg once daily ( n = 218 ) , 5 mg twice daily ( n = 219 ) or 10 mg once daily ( n = 220 ) , or placebo ( n = 107 ) as add‐on to stable‐dose metformin immediate release ( IR ) twice daily for 16 weeks . The primary endpoint was change from baseline in HbA1c at week 16 . At week 16 , change from baseline in HbA1c with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa . The adjusted mean ( 95 % confidence interval ) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11 % ( −0.26 , 0.03 ) , and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02 % ( −0.16 , 0.13 ) . All empagliflozin regimens were well tolerated ; thus , when used as add‐on to metformin IR in patients with T2DM , the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent OBJECTIVE To evaluate the efficacy and safety of dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin and sulfonylurea . RESEARCH DESIGN AND METHODS Patients with HbA1c of 7.0 % ( 53 mmol/mol ) to 10.5 % ( 91 mmol/mol ) receiving sulfonylurea and metformin were r and omized to receive dapagliflozin 10 mg/day ( n = 109 ) or placebo ( n = 109 ) for 24 weeks . RESULTS HbA1c ( baseline : dapagliflozin 8.08 % [ 65 mmol/mol ] ; placebo 8.24 % [ 67 mmol/mol ] ) and fasting plasma glucose ( baseline : dapagliflozin 167.4 mg/dL [ 9.29 mmol/L ] ; placebo 180.5 mg/dL [ 10.02 mmol/L ] ) significantly improved from baseline with dapagliflozin ( placebo-subtracted change –0.69 % [ –7.5 mmol/mol ] , P < 0.0001 ; –33.5 mg/dL [ –1.86 mmol/L ] , P < 0.0001 , respectively ) . More patients achieved a therapeutic glycemic response ( HbA1c < 7.0 % [ 53 mmol/mol ] ) with dapagliflozin ( 31.8 % ) versus placebo ( 11.1 % ) ( P < 0.0001 ) . Body weight and systolic blood pressure were significantly reduced from baseline over 24 and 8 weeks , respectively , with dapagliflozin ( placebo-subtracted change –2.1 kg , P < 0.0001 ; –3.8 mmHg , P = 0.0250 ) . Patients receiving dapagliflozin showed placebo-subtracted increases in total , LDL , and HDL cholesterol ( 11.4 mg/dL , P = 0.0091 ; 11.4 mg/dL , P = 0.0030 ; 2.2 mg/dL , P = 0.0172 , respectively ) with no change in LDL/HDL cholesterol ratio ( 0.1 ; P = 0.2008 ) or triglycerides ( –16.5 mg/dL ; P = 0.1755 ) . Adverse events occurred in 48.6 % of patients receiving dapagliflozin and 51.4 % receiving placebo . Significantly more patients with dapagliflozin compared with placebo experienced hypoglycemia ( 12.8 vs. 3.7 % ; P = 0.024 ) and genital infections ( 5.5 vs. 0 % ; P = 0.029 ) . Events of urinary tract infection were reported by 6.4 % of patients in both groups . CONCLUSIONS Dapagliflozin was well tolerated and effective over 24 weeks as add-on to metformin plus sulfonylurea . Adverse effects included hypoglycemia and genital infections OBJECTIVE To investigate the efficacy , safety , and tolerability of empagliflozin in patients with type 2 diabetes and hypertension . RESEARCH DESIGN AND METHODS Patients ( N = 825 ) with type 2 diabetes and hypertension ( mean seated systolic blood pressure [ SBP ] 130–159 mmHg and diastolic blood pressure [ DBP ] 80–99 mmHg ) were r and omized ( double blind ) to 10 mg or 25 mg empagliflozin or placebo once daily for 12 weeks . RESULTS At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h SBP ( ambulatory blood pressure monitoring [ ABPM ] ) was −3.44 mmHg ( 95 % CI −4.78 , −2.09 ) with 10 mg empagliflozin and −4.16 mmHg ( −5.50 , −2.83 ) with 25 mg empagliflozin ( both P < 0.001 ) . At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h DBP ( ABPM ) was −1.36 mmHg ( 95 % CI −2.15 , −0.56 ) with 10 mg empagliflozin and −1.72 mmHg ( 95 % CI −2.51 , −0.93 ) with 25 mg empagliflozin ( both P < 0.001 ) . Changes in office BP were consistent with ABPM . Adjusted mean difference versus placebo in change from baseline in HbA1c at week 12 was −0.62 % ( 95 % CI −0.72 , −0.52 ) ( −6.8 mmol/mol [ 95 % CI −7.9 , −5.7 ] ) with 10 mg empagliflozin and −0.65 % ( 95 % CI −0.75 , −0.55 ) ( −7.1 mmol/mol [ 95 % CI −8.2 , −6.0 ] ) with 25 mg empagliflozin ( both P < 0.001 ) . Empagliflozin was well tolerated . One patient on placebo and one patient on 10 mg empagliflozin reported events consistent with volume depletion . CONCLUSIONS Empagliflozin was associated with significant and clinical ly meaningful reductions in BP and HbA1c versus placebo and was well tolerated in patients with type 2 diabetes and hypertension Background This study evaluated the effect of empagliflozin on postpr and ial glucose ( PPG ) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients ( N = 60 ; baseline mean [ SD ] HbA1c 7.91 [0.80]% ; body mass index 24.3 [ 3.2 ] kg/m2 ) were r and omized to receive empagliflozin 10 mg ( n = 20 ) , empagliflozin 25 mg ( n = 19 ) or placebo ( n = 21 ) once daily as monotherapy for 28 days . A meal tolerance test and continuous glucose monitoring ( CGM ) for 24 hours were performed at baseline and on days 1 and 28 . The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast ( AUC1–4h for PPG ) at day 28 . Results Adjusted mean ( 95 % ) differences versus placebo in changes from baseline in AUC1 - 4h for PPG at day 1 were −97.1 ( −126.5 , −67.8 ) mg · h/dl with empagliflozin 10 mg and −91.6 ( −120.4 , −62.8 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −85.5 ( −126.0 , −45.0 ) mg · h/dl with empagliflozin 10 mg and −104.9 ( −144.8 , −65.0 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Adjusted mean ( 95 % CI ) differences versus placebo in change from baseline in 24-hour mean glucose ( CGM ) at day 1 were −20.8 ( −27.0 , −14.7 ) mg/dl with empagliflozin 10 mg and −23.9 ( −30.0 , −17.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −24.5 ( −35.4 , −13.6 ) mg/dl with empagliflozin 10 mg and −31.7 ( −42.5,-20.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Changes from baseline in mean amplitude of glucose excursions ( MAGE ; CGM ) were not significantly different with either empagliflozin dose versus placebo at either timepoint . Curves of mean glucose ( CGM ) did not change between baseline and day 1 or 28 with placebo , but shifted downward with empagliflozin . Percentage of time with glucose ≥70 to < 180 mg/dl increased from 52.0 % at baseline to 77.0 % at day 28 with empagliflozin 10 mg and from 55.0 % to 81.1 % with empagliflozin 25 mg , without increasing time spent with hypoglycemia . Conclusion Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.Trial registration Clinical trials.gov OBJECTIVE We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor , empagliflozin , added to multiple daily injections of insulin ( MDI insulin ) in obese patients with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS Patients inadequately controlled on MDI insulin ± metformin ( mean HbA1c 8.3 % [ 67 mmol/mol ] ; BMI 34.8 kg/m2 ; insulin dose 92 international units/day ) were r and omized and treated with once-daily empagliflozin 10 mg ( n = 186 ) , empagliflozin 25 mg ( n = 189 ) , or placebo ( n = 188 ) for 52 weeks . Insulin dose was to remain stable in weeks 1–18 , adjusted to meet glucose targets in weeks 19–40 , then stable in weeks 41–52 . The primary end point was change from baseline in HbA1c at week 18 . Secondary end points were changes from baseline in insulin dose , weight , and HbA1c at week 52 . RESULTS Adjusted mean ± SE changes from baseline in HbA1c were −0.50 ± 0.05 % ( −5.5 ± 0.5 mmol/mol ) for placebo versus −0.94 ± 0.05 % ( −10.3 ± 0.5 mmol/mol ) and −1.02 ± 0.05 % ( −11.1 ± 0.5 mmol/mol ) for empagliflozin 10 mg and empagliflozin 25 mg , respectively , at week 18 ( both P < 0.001 ) . At week 52 , further reductions with insulin titration result ed in changes from baseline in HbA1c of −0.81 ± 0.08 % ( −8.9 ± 0.9 mmol/mol ) , −1.18 ± 0.08 % ( −12.9 ± 0.9 mmol/mol ) , and −1.27 ± 0.08 % ( −13.9 ± 0.9 mmol/mol ) with placebo , empagliflozin 10 mg , and empagliflozin 25 mg , respectively , and final HbA1c of 7.5 % ( 58 mmol/mol ) , 7.2 % ( 55 mmol/mol ) , and 7.1 % ( 54 mmol/mol ) , respectively . More patients attained HbA1c < 7 % ( < 53 mmol/mol ) with empagliflozin ( 31–42 % ) versus placebo ( 21 % ; both P < 0.01 ) . Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses ( −9 to −11 international units/day ) and weight ( −2.4 to −2.5 kg ) versus placebo ( all P < 0.01 ) at week 52 . CONCLUSIONS In obese , difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses , empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements OBJECTIVE This study assessed the efficacy/safety of canagliflozin ( CANA ) , a sodium – glucose cotransporter 2 ( SGLT2 ) inhibitor , plus metformin extended-release ( MET ) initial therapy in drug-naïve type 2 diabetes . RESEARCH DESIGN AND METHODS This 26-week , double-blind , phase 3 study r and omized 1,186 patients to CANA 100 mg (CANA100)/MET , CANA 300 mg (CANA300)/MET , CANA100 , CANA300 , or MET . Primary end point was change in HbA1c at week 26 for combinations versus monotherapies . Secondary end points included noninferiority in HbA1c lowering with CANA monotherapy versus MET ; changes in fasting plasma glucose , body weight , and blood pressure ; and proportion of patients achieving HbA1c < 7.0 % ( < 53 mmol/mol ) . RESULTS From mean baseline HbA1c of 8.8 % ( 73 mmol/mol ) , CANA100/MET and CANA300/MET significantly lowered HbA1c versus MET ( median dose , 2,000 mg/day ) by –1.77 % , –1.78 % , and –1.30 % ( –19.3 , –19.5 , and –14.2 mmol/mol ; differences of −0.46 % and –0.48 % [ –5.0 and –5.2 mmol/mol ] ; P = 0.001 ) and versus CANA100 and CANA300 by –1.37 % and –1.42 % ( –15.0 and –15.5 mmol/mol ; differences of –0.40 % and –0.36 % [ –4.4 and –3.9 mmol/mol ] ; P = 0.001 ) . CANA100 and CANA300 monotherapy met noninferiority for HbA1c lowering and had significantly more weight loss versus MET ( –2.8 , –3.7 , and –1.9 kg [ –3.0 % , –3.9 % , and –2.1 % ] ; P = 0.016 and P = 0.002 ) . Greater attainment of HbA1c < 7.0 % ( 50 % , 57 % , and 43 % ) and significantly more weight loss ( –3.2 , –3.9 , and –1.9 kg [ –3.5 % , –4.2 % , and –2.1 % ] ; P = 0.001 ) occurred with CANA100/MET and CANA300/MET versus MET . The incidence of adverse events ( AEs ) related to SGLT2 inhibition ( genital mycotic infections , osmotic diuresis– and volume depletion – related AEs ) was higher in the CANA arms ( 0.4–4.4 % ) versus MET ( 0–0.8 % ) . AE-related discontinuation rates were 1.3–3.0 % across groups . The incidence of hypoglycemia was 3.0–5.5 % in the CANA arms and 4.6 % with MET . CONCLUSIONS Initial therapy with CANA plus MET was more effective and generally well tolerated versus each monotherapy in drug-naïve type 2 diabetes . CANA monotherapy demonstrated noninferior HbA1c lowering versus MET BACKGROUND Hypertension is a common comorbidity in patients with type 2 diabetes mellitus and a major risk factor for microvascular and macrovascular disease . Although the blood pressure-lowering effects of sodium-glucose cotransporter 2 ( SGLT2 ) inhibitors are already established , guidance is needed on how to use these drugs in patients already receiving antihypertensive therapy . We aim ed to compare blood pressure and glycaemic effects of the SGLT2 inhibitor dapagliflozin with placebo in patients with inadequately controlled type 2 diabetes mellitus and hypertension . METHODS In this double-blind , placebo-controlled , phase 3 study we enrolled patients from 311 centres in 16 countries across five continents . Patients had uncontrolled type 2 diabetes ( HbA1c 7·0%-10·5 % ; 53 - 91 mmol/mol ) and hypertension ( systolic 140 - 165 mm Hg and diastolic 85 - 105 mm Hg at both enrolment and r and omisation , and a mean 24 h blood pressure of ≥130/80 mm Hg by ambulatory monitoring within 1 week of r and omisation ) and were receiving oral antihyperglycaemic drugs , insulin , or both , plus a renin-angiotensin system blocker and an additional antihypertensive drug . Using an interactive voice-response system , we r and omly assigned ( 1:1 ) patients to dapagliflozin 10 mg once a day or to placebo , with r and omisation stratified by additional antihypertensive drug use and insulin use at baseline , in a block size of two . The co- primary endpoints were changes in seated systolic blood pressure and HbA1c measured in the full analysis set , which included all patients who received at least one dose of study drug and had both a baseline and at least one post-baseline measurement of efficacy . This trial is registered with Clinical Trials.gov , number NCT01195662 . FINDINGS Between Oct 29 , 2010 , and Oct 4 , 2012 , we r and omly assigned 225 patients to dapagliflozin and 224 to placebo . Seated systolic blood pressure was significantly reduced in the group assigned to dapagliflozin ( adjusted mean change from baseline -11·90 mm Hg [ 95 % CI -13·97 to -9·82 ] ) compared with those assigned to placebo ( -7·62 mm Hg [ -9·72 to -5·51 ] ; placebo-adjusted difference for dapagliflozin -4·28 mm Hg [ -6·54 to -2·02 ] ; p=0·0002 ) . Reductions in HbA1c concentrations were also significantly greater in patients assigned to dapagliflozin ( adjusted mean change from baseline -0·63 % [ 95 % CI -0·76 to -0·50 ] ) than in those assigned to placebo ( -0·02 % [ -0·15 to 0·12 ] ; placebo-adjusted difference -0·61 % [ -0·76 to -0·46 , ] ; p<0·0001 ) . In a post-hoc analysis , we found difference in blood pressure versus placebo was greater in patients receiving a β blocker ( -5·76 mm Hg [ 95 % CI -10·28 to -1·23 ] ) or a calcium-channel blocker ( -5·13 mm Hg , [ -9·47 to -0·79 ] ) as their additional antihypertensive drug than in those receiving a thiazide diuretic ( -2·38 mm Hg [ -6·16 to 1·40 ] ) . Adverse events were similar in the dapagliflozin and placebo groups ( 98 [ 44 % ] patients vs 93 [ 42 % ] , respectively , had at least one adverse event ) , with few adverse events related to renal function ( 1 % vs < 1 % ) or volume depletion ( < 1 % vs 0 % ) . INTERPRETATION Dapagliflozin 10 mg significantly improved blood pressure and HbA1c and was tolerated similarly to placebo . Its blood pressure-lowering properties were particularly favourable in patients already receiving a β blocker or calcium-channel blocker . Dapagliflozin could benefit patients with type 2 diabetes who need a diuretic-like effect to optimise control of blood pressure , adding meaningful efficacy to antihypertensive drug regimens . FUNDING Bristol-Myers Squibb , AstraZeneca Background Dapagliflozin ’s antihyperglycemic effects are mediated by inhibition of renal sodium-glucose cotransporter-2 ; therefore , renal safety of dapagliflozin was assessed . Methods Twelve double-blind , placebo-controlled , r and omized clinical trials were analyzed up to 24 weeks ( N = 4545 ) . Six of the 12 studies included long-term data for up to 102 weeks ( N = 3036 ) . Patients with type 2 diabetes with normal or mildly impaired renal function [ estimated glomerular filtration rate ( eGFR ) 60 to < 90 mL/min/1.73 m2 ] were treated with dapagliflozin ( 2.5 , 5 , or 10 mg/day ) or placebo . Renal adverse events ( AEs ) were assessed . Results Mean eGFR showed small transient reductions with dapagliflozin at week 1 , but returned to near baseline values by week 24 and remained stable to week 102 . Mean eGFR changes were not very different for dapagliflozin 2.5 , 5 and 10 mg versus placebo at 102 weeks : −0.74 , 2.52 and 1.38 versus 1.31 mL/min/1.73 m2 , respectively . Renal AEs were similar in frequency to placebo through 24 weeks ( 1.4 , 1.3 , 0.9 , and 0.9 % , respectively ) and 102 weeks ( 2.4 , 1.8 , 1.9 and 1.7 % , respectively ) . Few were serious ( 0.2 , 0.1 , 0 and 0.3 % , respectively , over 102 weeks ) . The most common renal event was serum creatinine increase . In sub-group analyses in patients ≥65 years of age or those with moderate renal impairment ( eGFR 30 to < 60 mL/min/1.73 m2 ) , renal AEs occurred more frequently with dapagliflozin than placebo . No events of acute tubular necrosis were reported . Conclusion In patients with normal or mildly impaired renal function , dapagliflozin is not associated with increased risk of acute renal toxicity or deterioration of renal function . All trials included in this analysis are registered at Clinical Trials.gov : NCT00263276 , NCT00972244 , NCT00528372 , NCT00736879 , NCT00528879 , NCT00855166 , NCT00357370 , NCT00680745 , NCT00683878 , NCT00673231 , NCT00643851 , NCT00859898 Aims To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes . Methods Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were r and omized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m2 ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . Results At week 18 , the adjusted mean ± st and ard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( −0.1 ± 0.8 mmol/mol ) for placebo , compared with −0.6 ± 0.1 % ( −6.2 ± 0.8 mmol/mol ) and −0.7 ± 0.1 % ( −7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p < 0.001 ) . At week 78 , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all p < 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35–36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively . Conclusions Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo Aims /hypothesisThe aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin . Methods This r and omised , double-blind , four-arm , parallel-group , Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012 . Participants ( N = 1,284 ) with type 2 diabetes aged ≥18 and ≤80 years who had inadequate glycaemic control ( HbA1c ≥7.0 % [ 53 mmol/mol ] and ≤10.5 % [ 91 mmol/mol ] ) on metformin therapy received canagliflozin 100 mg or 300 mg , sitagliptin 100 mg , or placebo ( n = 368 , 367 , 366 , 183 , respectively ) for a 26 week , placebo- and active-controlled period followed by a 26 week , active-controlled period ( placebo group switched to sitagliptin [ placebo/sitagliptin ] ) and were included in the modified intent-to-treat analysis set . R and omisation was performed using a computer-generated schedule ; participants , study centres and the sponsor were blinded to group assignment . The primary endpoint was change from baseline in HbA1c at week 26 ; secondary endpoints included changes in HbA1c ( week 52 ) and fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( BP ; weeks 26 and 52 ) . Adverse events ( AEs ) were recorded throughout the study . Results At week 26 , canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo ( −0.79 % , –0.94 % , –0.17 % , respectively ; p < 0.001 ) . At week 52 , canagliflozin 100 mg and 300 mg demonstrated non-inferiority , and canagliflozin 300 mg demonstrated statistical superiority , to sitagliptin in lowering HbA1c ( −0.73 % , –0.88%,–0.73 % , respectively ) ; differences ( 95 % CI ) vs sitagliptin were 0 % ( −0.12 , 0.12 ) and −0.15 % ( −0.27 , –0.03 ) , respectively . Canagliflozin 100 mg and 300 mg reduced body weight vs placebo ( week 26 : –3.7 % , –4.2 % , –1.2 % , respectively ; p < 0.001 ) and sitagliptin ( week 52 : –3.8 % , –4.2 % , –1.3 % , respectively ; p < 0.001 ) . Both canagliflozin doses reduced FPG and systolic BP vs placebo ( week 26 ) and sitagliptin ( week 52 ) ( p < 0.001 ) . Overall AE and AE-related discontinuation rates were generally similar across groups , but higher with canagliflozin 100 mg . Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin ; few led to discontinuations . Hypoglycaemia incidence was higher with canagliflozin . Conclusions /interpretationCanagliflozin improved glycaemia and reduced body weight vs placebo ( week 26 ) and sitagliptin ( week 52 ) and was generally well tolerated in patients with type 2 diabetes on metformin . Clinical trial registry Clinical Trials.gov NCT01106677 Funding This study was supported by Janssen Research & Development , LLC BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or placebo . The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes AIMS This study investigated the efficacy and tolerability of empagliflozin as add-on to pioglitazone ± metformin in patients with type 2 diabetes ( T2DM ) . METHODS Patients with HbA1c ≥7 and ≤10 % were r and omized and treated with once daily empagliflozin 10 mg ( n = 165 ) , empagliflozin 25 mg ( n = 168 ) or placebo ( n = 165 ) as add-on to pioglitazone ± metformin for 24 weeks . Endpoints included changes from baseline in HbA1c ( primary endpoint ) , fasting plasma glucose ( FPG ) and body weight at week 24 . RESULTS Adjusted mean ± st and ard error changes in HbA1c were -0.6 ± 0.07 % and -0.7 ± 0.07 % with empagliflozin 10 mg and 25 mg , respectively , vs. -0.1 ± 0.07 % with placebo ( both p < 0.001 ) . More patients with HbA1c ≥7 % at baseline achieved HbA1c < 7 % with empagliflozin 10 mg ( 23.8 % ) and 25 mg ( 30.0 % ) vs. placebo ( 7.7 % ) ( both p < 0.001 ) . FPG decreased with empagliflozin ( -0.94 mmol/l for 10 mg and -1.22 mmol/l for 25 mg ) and increased with placebo ( + 0.36 mmol/l ; both p < 0.001 ) . Adjusted mean ± st and ard error changes in weight were -1.62 ± 0.21 kg and -1.47 ± 0.21 kg with empagliflozin 10 mg and 25 mg , respectively , vs. + 0.34 ± 0.21 kg with placebo ( both p < 0.001 ) . Similar proportions of patients reported adverse events with empagliflozin ( 67.3 - 71.4 % ) and placebo ( 72.7 % ) . Confirmed hypoglycaemia was reported by 1.2 - 2.4 % of patients on empagliflozin and 1.8 % on placebo . CONCLUSION Empagliflozin 10 mg and 25 mg once daily for 24 weeks as add-on to pioglitazone ± metformin reduced HbA1c , FPG and weight and were well tolerated in patients with T2DM OBJECTIVE To evaluate the efficacy and safety of empagliflozin/linagliptin in subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS Subjects not receiving antidiabetes therapy for ≥12 weeks were r and omized to empagliflozin 25 mg/linagliptin 5 mg ( n = 137 ) , empagliflozin 10 mg/linagliptin 5 mg ( n = 136 ) , empagliflozin 25 mg ( n = 135 ) , empagliflozin 10 mg ( n = 134 ) , or linagliptin 5 mg ( n = 135 ) for 52 weeks . The primary end point was change from baseline in HbA1c at week 24 . RESULTS Mean HbA1c at baseline was 7.99–8.05 % ( 64 mmol/mol ) . At week 24 , adjusted mean ( SE ) changes from baseline in HbA1c with empagliflozin 25 mg/linagliptin 5 mg , empagliflozin 10 mg/linagliptin 5 mg , empagliflozin 25 mg , empagliflozin 10 mg , and linagliptin 5 mg were −1.08 (0.06)% ( −11.8 [ 0.7 ] mmol/mol ) , −1.24 (0.06)% ( −13.6 [ 0.7 ] mmol/mol ) , −0.95 (0.06)% ( −10.4 [ 0.7 ] mmol/mol ) , −0.83 (0.06)% ( −9.1 [ 0.7 ] mmol/mol ) , and −0.67 (0.06)% ( −7.3 [ 0.7 ] mmol/mol ) , respectively . Reductions in HbA1c were significantly greater for empagliflozin 25 mg/linagliptin 5 mg compared with linagliptin 5 mg ( P < 0.001 ) but not compared with empagliflozin 25 mg and were significantly greater for empagliflozin 10 mg/linagliptin 5 mg compared with the individual components ( P < 0.001 for both ) . At week 24 , 55.4 % , 62.3 % , 41.5 % , 38.8 % , and 32.3 % of subjects with baseline HbA1c ≥7 % ( ≥53 mmol/mol ) reached HbA1c < 7 % with empagliflozin 25 mg/linagliptin 5 mg , empagliflozin 10 mg/linagliptin 5 mg , empagliflozin 25 mg , empagliflozin 10 mg , and linagliptin 5 mg , respectively . Efficacy was maintained at week 52 . The proportion of subjects with adverse events ( AEs ) over 52 weeks was similar across groups ( 68.9–81.5 % ) , with no confirmed hypoglycemic AEs . CONCLUSIONS Reductions from baseline in HbA1c with empagliflozin/linagliptin were significantly different versus linagliptin and empagliflozin 10 mg but not versus empagliflozin 25 mg . Empagliflozin/linagliptin was well tolerated Aims To evaluate the efficacy and safety of titrated canagliflozin , a sodium glucose co‐transporter 2 inhibitor , in patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled on metformin and sitagliptin . Methods In this r and omized , double‐blind study , patients with T2DM ( N = 218 ) on metformin ≥1500 mg/day and sitagliptin 100 mg received canagliflozin 100 mg or placebo . After 6 weeks , the canagliflozin dose was increased from 100 to 300 mg ( or from placebo to matching placebo ) if all of the following criteria were met : baseline estimated glomerular filtration rate ≥70 ml/min/1.73 m2 ; fasting self‐monitored blood glucose ≥5.6 mmol/l ( ≥100 mg/dl ) ; and no volume depletion – related adverse events ( AEs ) within 2 weeks before dose increase . Endpoints included change in glycated haemoglobin ( HbA1c ) at week 26 ( primary ) ; proportion of patients achieving HbA1c < 7.0 % ; and changes in fasting plasma glucose ( FPG ) , body weight and systolic blood pressure ( SBP ) . Safety was assessed using AE reports . Results Overall , 85.4 % of patients were titrated to canagliflozin 300 mg or matching placebo ( mean ± st and ard deviation time to titration 6.2 ± 0.8 weeks ) . At week 26 , canagliflozin ( pooled 100 and 300 mg ) demonstrated superiority in HbA1c reduction versus placebo ( −0.91 % vs. −0.01 % ; p < 0.001 ) . Canagliflozin provided significant reductions in FPG , body weight and SBP compared with placebo ( p < 0.001 ) . The overall AE incidence was 39.8 and 44.4 % for canagliflozin and placebo , respectively . Canagliflozin was associated with an increased incidence of genital mycotic infections . Conclusions Titrated canagliflozin significantly improved HbA1c , FPG , body weight and SBP , and was generally well tolerated over 26 weeks in patients with T2DM as add‐on to metformin and sitagliptin OBJECTIVE To determine whether dapagliflozin , which selectively inhibits renal glucose reabsorption , lowers hyperglycemia in patients with type 2 diabetes that is poorly controlled with high insulin doses plus oral antidiabetic agents ( OADs ) . RESEARCH DESIGN AND METHODS This was a r and omized , double-blind , three-arm parallel-group , placebo-controlled , 26-center trial ( U.S. and Canada ) . Based on data from an insulin dose-adjustment setting cohort ( n = 4 ) , patients in the treatment cohort ( n = 71 ) were r and omly assigned 1:1:1 to placebo , 10 mg dapagliflozin , or 20 mg dapagliflozin , plus OAD(s ) and 50 % of their daily insulin dose . The primary outcome was change from baseline in A1C at week 12 ( dapagliflozin vs. placebo , last observation carried forward [ LOCF ] ) . RESULTS At week 12 ( LOCF ) , the 10- and 20-mg dapagliflozin groups demonstrated −0.70 and −0.78 % mean differences in A1C change from baseline versus placebo . In both dapagliflozin groups , 65.2 % of patients achieved a decrease from baseline in A1C ≥0.5 % versus 15.8 % in the placebo group . Mean changes from baseline in fasting plasma glucose ( FPG ) were + 17.8 , + 2.4 , and −9.6 mg/dl ( placebo , 10 mg dapagliflozin , and 20 mg dapagliflozin , respectively ) . Postpr and ial glucose ( PPG ) reductions with dapagliflozin also showed dose dependence . Mean changes in total body weight were −1.9 , −4.5 , and −4.3 kg ( placebo , 10 mg dapagliflozin , and 20 mg dapagliflozin ) . Overall , adverse events were balanced across all groups , although more genital infections occurred in the 20-mg dapagliflozin group than in the placebo group . CONCLUSIONS In patients receiving high insulin doses plus insulin sensitizers who had their baseline insulin reduced by 50 % , dapagliflozin decreased A1C , produced better FPG and PPG levels , and lowered weight more than placebo Abstract Aims / Introduction To determine the efficacy and safety of ipragliflozin in combination with metformin in Asian patients with type 2 diabetes mellitus . Material s and Methods This phase 3 , multicenter , placebo‐controlled , double‐blind , parallel‐group study was carried out at 18 sites in Korea and 12 sites in Taiwan . After an 8‐week washout period for patients using drugs other than metformin and a 2‐week run‐in period , patients were r and omized to either 50 mg ipragliflozin or a placebo for 24 weeks while continuing metformin . Efficacy outcomes included the changes in hemoglobin A1c , fasting plasma glucose ( FPG ) and bodyweight from baseline to the end of treatment ( with last observation carried forward ) . Safety outcomes included treatment‐emergent adverse events . Results Between November 2011 and January 2013 , 171 patients were r and omized to and administered ipragliflozin ( n = 87 ) or a placebo ( n = 83 ) . The mean changes ( st and ard deviation ) in hemoglobin A1c were −0.94 % ( 0.75 % ) and −0.47 % ( 0.81 % ) in the ipragliflozin and placebo groups , respectively ( between‐group difference −0.46 % , P < 0.001 ) . The changes in fasting plasma glucose and bodyweight were also significantly greater in the ipragliflozin group , with between‐group differences of −14.1 mg/dL and −1.24 kg , respectively ( both P < 0.001 ) . The most common treatment‐emergent adverse events ( ipragliflozin vs placebo ) were upper respiratory tract infection ( 9.2 % vs 12.0 % ) and urinary tract infection ( 6.9 % vs 2.4 % ) . Conclusions These results show that ipragliflozin is effective and well tolerated when used in combination with metformin in Asian patients with type 2 diabetes mellitus Canagliflozin is a sodium glucose co‐transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus ( T2DM ) . This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [ CKD ; estimated glomerular filtration rate ( eGFR ) ≥30 and < 50 ml/min/1.73 m2 ] In patients with diabetes , glycemic improvement by sodium-glucose cotransporter-2 inhibition depends on the kidney 's ability to filter glucose . Dapagliflozin , a sodium-glucose cotransporter-2 inhibitor , reduces hyperglycemia in patients with diabetes and normal or mildly impaired renal function . In this r and omized , double-blind , placebo-controlled study we assessed daily treatment with dapagliflozin in 252 patients with inadequately controlled type 2 diabetes and moderate renal impairment . The primary endpoint , the mean change in HbA1c , was not statistically different from placebo after 24 weeks ( −0.41 % and −0.44 % for 5- and 10-mg doses , respectively , and −0.32 % for placebo ) . The mean weight change from baseline was −1.54 and −1.89 kg for the 5- and 10-mg doses , respectively , and + 0.21 kg for placebo . The mean systolic and diastolic blood pressure decreased in the dapagliflozin groups compared to placebo . Through 104 weeks , 13 patients receiving dapagliflozin and no patients receiving placebo experienced bone fracture . At 1 week , the mean serum creatinine increased with dapagliflozin 5 mg ( + 0.13 mg/dl ) and 10 mg ( + 0.18 mg/dl ) and did not change further after 104 weeks . Mean serum electrolytes did not change in any group , and there were fewer episodes of hyperkalemia with dapagliflozin than placebo . Thus , in patients with moderate renal impairment , dapagliflozin did not improve glycemic control , but reduced weight and blood pressure Aims Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus ( T2DM ) . This r and omised , double-blind , placebo-controlled , Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM . Methods Patients ( N = 469 ) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension . Prespecified primary end-point was change in HbA1c at 26 weeks . Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c < 7.0 % , change in fasting plasma glucose ( FPG ) and systolic blood pressure , and per cent change in body weight , high-density lipoprotein cholesterol , and triglycerides ( weeks 26 and 52 ) . Results HbA1c was significantly reduced with canagliflozin 100 and 300 mg vs. placebo at week 26 ( –0.85 % , –1.06 % , and –0.13 % ; p < 0.001 ) ; these reductions were maintained at week 52 ( –0.74 % , –0.96 % , and 0.01 % ) . Both canagliflozin doses reduced FPG and body weight vs. placebo at week 26 ( p < 0.001 ) and week 52 . Overall adverse event ( AE ) rates were similar across groups over 52 weeks , with higher rates of genital mycotic infections and osmotic diuresis-related AEs seen with canagliflozin vs. placebo ; these led to few discontinuations . Increased incidence of documented , but not severe , hypoglycaemia episodes was seen with canagliflozin vs. placebo . Conclusions Canagliflozin improved glycaemic control , reduced body weight , and was generally well tolerated in T2DM patients on metformin plus sulphonylurea over 52 weeks Aim To evaluate the efficacy/safety of canagliflozin twice daily ( BID ) compared with placebo in patients with type 2 diabetes mellitus ( T2DM ) on metformin . Methods In this 18-week , r and omized , double-blind , placebo-controlled study , patients ( N = 279 ) at 60 centers in 7 countries received canagliflozin 50 or 150 mg or placebo BID . The pre-specified primary endpoint was change from baseline in HbA1c at Week 18 . Pre-specified secondary endpoints included proportion of patients reaching HbA1c < 7.0 % , change in fasting plasma glucose ( FPG ) , and percent change in body weight ; changes in systolic blood pressure ( BP ) and fasting plasma lipids were also evaluated . Adverse events ( AEs ) were recorded throughout the study . Results From a mean baseline HbA1c of 7.6 % ( 60 mmol/mol ) , canagliflozin 50 and 150 mg BID significantly reduced HbA1c compared with placebo at Week 18 ( −0.45 % , −0.61 % , −0.01 % [ −5 , −7 , −0.1 mmol/mol ] , respectively ; P < 0.001 ) . More patients achieved HbA1c < 7.0 % with canagliflozin than placebo ( P < 0.05 ) . Relative to placebo , both canagliflozin doses significantly lowered FPG and body weight ( P < 0.001 ) , and reduced systolic BP . Overall AE incidence was 35.5 % , 40.9 % , and 36.6 % with canagliflozin 50 and 150 mg BID and placebo , respectively . Canagliflozin was associated with increased incidences of urinary tract infections , female genital mycotic infections , and osmotic diuresis-related AEs ; these led to few discontinuations . The incidence of documented hypoglycemia was low across groups . Conclusions Canagliflozin 50 and 150 mg BID provided significant glycemic efficacy and body weight reduction , and were generally well tolerated in patients with T2DM on background metformin . Clinical Trials.gov Identifier : BACKGROUND Dapagliflozin , a selective inhibitor of sodium-glucose cotransporter 2 , may improve glycemic control with a lower dose of insulin and attenuate the associated weight gain in patients with inadequate control despite high doses of insulin . OBJECTIVE To evaluate the efficacy and safety of adding dapagliflozin therapy in patients whose type 2 diabetes mellitus is inadequately controlled with insulin with or without oral antidiabetic drugs . DESIGN A 24-week , r and omized , placebo-controlled , multicenter trial followed by a 24-week extension period . An additional 56-week extension period is ongoing . ( Clinical Trials.gov registration number : NCT00673231 ) SETTING 126 centers in Europe and North America from 30 April 2008 to 19 November 2009 . PATIENTS 808 patients with inadequately controlled type 2 diabetes mellitus receiving at least 30 U of insulin daily , with or without up to 2 oral antidiabetic drugs . INTERVENTION Patients were r and omly assigned in a 1:1:1:1 ratio and allocated with a computer-generated scheme to receive placebo or 2.5 , 5 , or 10 mg of dapagliflozin , once daily , for 48 weeks . MEASUREMENTS The primary outcome was change in hemoglobin A(1c ) from baseline to 24 weeks . Secondary outcomes included changes in body weight , insulin dose , and fasting plasma glucose level at 24 weeks and during the 24-week extension period . Adverse events were evaluated throughout both 24-week periods . RESULTS 800 patients were analyzed . After 24 weeks , mean hemoglobin A(1c ) decreased by 0.79 % to 0.96 % with dapagliflozin compared with 0.39 % with placebo ( mean difference , -0.40 % [ 95 % CI , -0.54 % to -0.25 % ] in the 2.5-mg group , -0.49 % [ CI , -0.65 % to -0.34 % ] in the 5-mg group , and -0.57 % [ CI , -0.72 % to -0.42 % ] in the 10-mg group ) . Daily insulin dose decreased by 0.63 to 1.95 U with dapagliflozin and increased by 5.65 U with placebo ( mean difference , -7.60 U [ CI , -10.32 to -4.87 U ] in the 2.5-mg group , -6.28 U [ CI , -8.99 to -3.58 U ] in the 5-mg group , and -6.82 U [ CI , -9.56 to -4.09 U ] in the 10-mg group ) . Body weight decreased by 0.92 to 1.61 kg with dapagliflozin and increased by 0.43 kg with placebo ( mean differences , -1.35 kg [ CI , -1.90 to -0.80 kg ] in the 2.5-mg group , -1.42 kg [ CI , -1.97 to -0.88 kg ] in the 5-mg group , and -2.04 kg [ CI , -2.59 to -1.48 kg ] in the 10-mg group ) . These effects were maintained at 48 weeks . Compared with the placebo group , patients in the pooled dapagliflozin groups had a higher rate of hypoglycemic episodes ( 56.6 % vs. 51.8 % ) , events suggesting genital infection ( 9.0 % vs. 2.5 % ) , and events suggesting urinary tract infection ( 9.7 % vs. 5.1 % ) . LIMITATION Insulin doses were not titrated to target , and the study was not design ed to evaluate long-term safety . CONCLUSION Dapagliflozin improves glycemic control , stabilizes insulin dosing , and reduces weight without increasing major hypoglycemic episodes in patients with inadequately controlled type 2 diabetes mellitus . PRIMARY FUNDING SOURCE AstraZeneca and Bristol-Myers Squibb To evaluate the efficacy and safety of twice‐daily dosing of dapagliflozin and metformin , exploring the feasibility of a fixed‐dose combination AIMS Progressive deterioration of glycaemic control in type 2 diabetes mellitus ( T2DM ) often requires treatment intensification . Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 ( SGLT2 ) . We assessed the efficacy , safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM . METHODS This 24-week , r and omized , double-blind , placebo-controlled , parallel-group , international , multicentre trial ( Clinical Trials.gov NCT00680745 ) enrolled patients with uncontrolled T2DM [ haemoglobin A1c ( HbA1c ) 7 - 10 % ] receiving sulphonylurea monotherapy . Adult patients ( n = 597 ) were r and omly assigned to placebo or dapagliflozin ( 2.5 , 5 or 10 mg/day ) added to open-label glimepiride 4 mg/day for 24 weeks . Primary endpoint was HbA1c mean change from baseline at 24 weeks . Secondary endpoints included change in body weight and other glycaemic parameters . RESULTS At 24 weeks , HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58 , -0.63 , -0.82 % , respectively ( all p < 0.0001 vs. placebo by Dunnett 's procedure ) . Corresponding body weight and fasting plasma glucose values were -0.72 , -1.18 , -1.56 , -2.26 kg and -0.11 , -0.93 , -1.18 , -1.58 mmol/l , respectively . In placebo versus dapagliflozin groups , serious adverse events were 4.8 versus 6.0 - 7.1 % ; hypoglycaemic events 4.8 versus 7.1 - 7.9 % ; events suggestive of genital infection 0.7 versus 3.9 - 6.6 % ; and events suggestive of urinary tract infection 6.2 versus 3.9 - 6.9 % . No kidney infections were reported . CONCLUSIONS Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c , reduced weight and was generally well tolerated , although events suggestive of genital infections were reported more often in patients receiving dapagliflozin BACKGROUND We aim ed to investigate the efficacy and tolerability of empagliflozin , an oral , potent , and selective inhibitor of sodium-glucose co-transporter 2 , in patients with type 2 diabetes who had not received drug treatment in the preceding 12 weeks . METHODS In our multicentre , r and omised , placebo-controlled , phase 3 trial , we enrolled adults ( aged ≥18 years ) who had not received oral or injected anti-diabetes treatment in the previous 12 weeks . Eligible patients had HbA1c concentrations of 7 - 10 % . We r and omly allocated patients ( 1:1:1:1 ) with a computer-generated r and om sequence , stratified by region , HbA1c , and estimated glomerular filtration rate at screening , to placebo , empagliflozin 10 mg , empagliflozin 25 mg , or sitagliptin 100 mg once daily for 24 weeks . Patients and investigators were masked to treatment assignment . The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in all r and omly allocated patients who were treated with at least one dose of study drug and had a baseline HbA1c value . This study is completed and registered with Clinical Trials.gov , number NCT01177813 . FINDINGS Between Aug 12 , 2010 , and March 19 , 2012 , we r and omly allocated 228 patients to receive placebo , 224 to receive empagliflozin 10 mg , 224 to receive empagliflozin 25 mg , and 223 to receive sitagliptin . Compared with placebo , adjusted mean differences in change from baseline HbA1c at week 24 were -0·74 % ( 95 % CI -0·88 to -0·59 ; p<0·0001 ) for empagliflozin 10 mg , -0·85 % ( -0·99 to -0·71 ; p<0·0001 ) for empagliflozin 25 mg , and -0·73 % ( -0·88 to -0·59 ; p<0·0001 ) for sitagliptin . 140 ( 61 % ) patients in the placebo group reported adverse events ( four [ 2 % ] severe and six [ 3 % ] serious ) , as did 123 ( 55 % ) patients in the empagliflozin 10 mg group ( eight [ 4 % ] severe and eight [ 4 % ] serious ) , 135 ( 60 % ) patients in the empagliflozin 25 mg group ( seven [ 3 % ] severe and five [ 2 % ] serious ) , and 119 ( 53 % ) patients in the sitagliptin group ( five [ 2 % ] severe and six [ 3 % ] serious ) . INTERPRETATION Empagliflozin provides a tolerable and efficacious strategy to reduce HbA1c in patients with type 2 diabetes who had not previously received drug treatment . FUNDING Boehringer Ingelheim and Eli Lilly BACKGROUND Metformin is the recommended first-line pharmacotherapy for patients with type 2 diabetes . There is no consensus on the optimum second-line pharmacotherapy . We compared the efficacy and safety of the sodium glucose cotransporter 2 inhibitor empagliflozin and the sulfonylurea glimepiride as add-on to metformin in patients with type 2 diabetes . METHODS In this double-blind phase 3 trial , patients ( aged ≥18 years ) with type 2 diabetes and HbA1c concentrations of 7 - 10 % , despite metformin treatment and diet and exercise counselling , were r and omly assigned in a 1:1 ratio with a computer-generated r and om sequence , stratified by HbA1c , estimated glomerular filtration rate ( eGFR ) , and region , to empagliflozin ( 25 mg once daily , orally ) or glimepiride ( 1 - 4 mg once daily , orally ) as add-on to metformin for 104 weeks . Patients and investigators were masked to treatment assignment . The primary endpoint was change from baseline in HbA1c levels at weeks 52 and 104 . Differences in the primary endpoint were first tested for non-inferiority ( based on a margin of 0·3 % ) . If non-inferiority was shown , differences in the primary endpoint at week 104 were then tested for superiority . Analysis was done on the full- analysis set-ie , patients who were treated with at least one dose of study drug and had a baseline HbA1c value . This study is registered with Clinical Trials.gov , number NCT01167881 . A 104-week extension is ongoing . FINDINGS Between August , 2010 , and June , 2011 , 1549 patients were r and omly assigned to receive empagliflozin ( n=769 ) or glimepiride ( n=780 ) ; four patients in the empagliflozin group did not receive the assigned treatment . Empagliflozin was non-inferior to glimepiride at both timepoints . At week 104 , adjusted mean difference in change from baseline in HbA1c with empagliflozin versus glimepiride was -0·11 % ( 95 % CI -0·19 to -0·02 ; p=0·0153 for superiority ) . Adverse events were reported in 661 ( 86 % ) patients treated with empagliflozin and 673 ( 86 % ) patients treated with glimepiride . Severe adverse events were reported in 72 ( 9 % ) patients in the empagliflozin group and 68 ( 9 % ) in the glimepiride group . Serious adverse events were reported in 119 ( 16 % ) patients in the empagliflozin group and 89 ( 11 % ) in the glimepiride group . Confirmed hypoglycaemic adverse events ( plasma glucose ≤3·9 mmol/L or requiring assistance ) at week 104 were reported in 19 ( 2 % ) patients treated with empagliflozin and 189 ( 24 % ) patients treated with glimepiride . INTERPRETATION Empagliflozin might be an effective and a well tolerated second-line treatment option for patients with type 2 diabetes who have not achieved good glycaemic control on metformin . FUNDING Boehringer Ingelheim and Eli Lilly OBJECTIVE Although initially effective , sulfonylureas are associated with poor glycemic durability , weight gain , and hypoglycemia . Dapagliflozin , a selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects . We compared the efficacy , safety , and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This 52-week , double-blind , multicenter , active-controlled , noninferiority trial r and omized patients with type 2 diabetes ( baseline mean HbA1c , 7.7 % ) , who were receiving metformin monotherapy , to add-on dapagliflozin ( n = 406 ) or glipizide ( n = 408 ) up-titrated over 18 weeks , based on glycemic response and tolerability , to ≤ 10 or ≤ 20 mg/day , respectively . RESULTS The primary end point , adjusted mean HbA1c reduction with dapagliflozin ( -0.52 % ) compared with glipizide ( -0.52 % ) , was statistically noninferior at 52 weeks . Key secondary end points : dapagliflozin produced significant adjusted mean weight loss ( -3.2 kg ) versus weight gain ( 1.2 kg ; P < 0.0001 ) with glipizide , significantly increased the proportion of patients achieving ≥ 5 % body weight reduction ( 33.3 % ) versus glipizide ( 2.5 % ; p < 0.0001 ) , and significantly decreased the proportion experiencing hypoglycemia ( 3.5 % ) versus glipizide ( 40.8 % ; p < 0.0001 ) . Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to st and ard treatment and rarely led to study discontinuation . CONCLUSIONS Despite similar 52-week glycemic efficacy , dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin . Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors Background / Aims : Some sodium glucose co-transporter 2 ( SGLT2 ) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus ( T2DM ) with an estimated glomerular filtration rate ( eGFR ) of ≥45 ml/min/1.73 m2 . The efficacy and safety of canagliflozin , an approved SGLT2 inhibitor , was evaluated in patients with stage 3 chronic kidney disease ( CKD ; eGFR ≥30 to < 60 ml/min/1.73 m2 ) . Methods : This analysis used integrated data from four r and omized , placebo-controlled , phase 3 studies that enrolled patients with T2DM and stage 3 CKD . Results are presented for the overall population as well as subgroups with stage 3a CKD ( eGFR ≥45 and < 60 ml/min/1.73 m2 ) and stage 3b CKD ( eGFR ≥30 and < 45 ml/min/1.73 m2 ) . Results : Among all subjects studied with stage 3 CKD , placebo-subtracted reductions in HbA1c ( -0.38 and -0.47 % ; p < 0.001 ) , body weight ( -1.6 and -1.9 % ; p < 0.001 ) , and systolic blood pressure ( -2.8 and -4.4 mm Hg ; p < 0.01 ) were seen with canagliflozin 100 and 300 mg , respectively . Decreases in HbA1c , body weight , and systolic blood pressure were examined in the stage 3a and 3b CKD subgroups , with greater decreases in HbA1c , -0.47 % ( -0.61 , -0.32 ) and body weight in subjects in stage 3a CKD , -1.8 % ( -2.3 , -1.2 ) with canagliflozin 100 mg . Initial declines in eGFR were seen early following treatment initiation with canagliflozin , but trended towards baseline over time . The most common adverse events with canagliflozin included genital mycotic infections and adverse events related to reduced intravascular volume likely secondary to osmotic diuresis . Conclusion : In subjects with T2DM and stage 3 CKD , canagliflozin reduced HbA1c , body weight , and blood pressure , and was generally well tolerated |
2,133 | 27,301,766 | Cost savings were most sensitive to the proportion of treatment-resistant patients who received clozapine , decrease in inpatient days , cost of inpatient stays , clozapine response rate , and number of patients with treatment-resistant schizophrenia .
Increased clozapine utilization would result in net cost savings for the VHA | OBJECTIVE In most setting s , less than 25 % of patients with treatment-resistant schizophrenia receive clozapine , the only medication proven effective for treatment-resistant schizophrenia .
Therefore , a business case analysis was conducted to assess whether increasing clozapine utilization for treatment-resistant schizophrenia in a health care system would result in direct health care cost savings . | BACKGROUND Few controlled studies have compared the efficacy of clozapine and risperidone in treatment-refractory schizophrenic patients . The present study investigates the efficacy of both clozapine and risperidone on psychopathologic and neurocognitive measures in a prospect i ve 12-week open-label trial in treatment-refractory schizophrenic patients from state psychiatric hospitals . METHOD Thirty-five DSM-IV schizophrenic patients with a documented history of nonresponse to typical neuroleptics were treated with either clozapine or risperidone . Response was assessed every 2 weeks by independent raters with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions ( CGI ) scale , neurologic rating scales , and plasma drug levels . Neurocognitive tests were administered at baseline and week 12 . RESULTS Both clozapine and risperidone brought about significant ( p < .003 ) overall improvement in psychopathology . However , clozapine was numerically superior to risperidone on PANSS total scores and PANSS positive , negative , excitement , and cognitive factors . Extrapyramidal side effects were minimal for clozapine , whereas some were present for risperidone . Patients taking risperidone improved significantly in the beginning stages of the study and remained stable thereafter . Patients taking clozapine showed a gradual improvement that occurred over the entire length of the trial . Neurocognitive measures showed minimal improvement and did not differentiate between the 2 medication groups . CONCLUSION Both clozapine and risperidone were comparably effective across a wide spectrum of psychopathologic measures . While the efficacy of clozapine was only numerically superior to that of risperidone , it was associated with fewer extrapyramidal side effects and with progressive improvement over the 12-week treatment period , suggesting that in longer trials clozapine may prove to be superior to risperidone in neuroleptic-refractory patients This 18-week , r and omized , flexible-dose , double-blind , double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients . Patients had a DSM-IV diagnosis of schizophrenia , a history of resistance and /or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses , PANSS score > or=80 , and CGI-S score > or=4 . Patients were r and omized to ziprasidone ( 80 - 160 mg/day , n=73 ) or clozapine ( 250 - 600 mg/day , n=74 ) . On the primary ITT-LOCF analysis , baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone ( -25.0+/-22.0 , 95 % CI -30.2 to -19.8 ) and clozapine ( -24.5+/-22.5 , 95 % CI -29.7 to -19.2 ) groups . A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms . There were also significant improvements on PANSS subscales , CGI-S , CG-I , CDSS , and GAF , without between-drug differences . The two treatment groups had similar rates of early discontinuations due to AEs . AEs were mostly of similar mild-moderate severity in the two groups . There were also no detrimental effects on prolactin , renal and liver function , hematology , and cardiovascular parameters . However , ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores . Moreover , when compared with clozapine , ziprasidone also had a more favorable metabolic profile , with significant endpoint differences in weight , fasting glucose , total cholesterol , LDL cholesterol , and triglycerides . In conclusion , this trial indicates that both ziprasidone and clozapine , having comparable efficacy coupled with satisfactory general safety and tolerability , may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and /or intolerance to antipsychotics . The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians , at least in the presence of patients at high risk for metabolic disorders OBJECTIVE When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug , it is unclear what other antipsychotic to switch to and when to use clozapine . In this study , the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness ( CATIE ) investigation . METHOD Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone in phase 1 or 1B of the trials , primarily because of inadequate efficacy , were r and omly assigned to open-label treatment with clozapine ( N=49 ) or blinded treatment with another newer atypical antipsychotic not previously received in the trial ( olanzapine [ N=19 ] , quetiapine [ N=15 ] , or risperidone [ N=16 ] ) . RESULTS Time until treatment discontinuation for any reason was significantly longer for clozapine ( median=10.5 months ) than for quetiapine ( median=3.3 ) , or risperidone ( median=2.8 ) , but not for olanzapine ( median=2.7 ) . Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine , quetiapine , or risperidone . At 3-month assessment s , Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine . One patient treated with clozapine developed agranulocytosis , and another developed eosinophilia ; both required treatment discontinuation . CONCLUSIONS For these patients with schizophrenia who prospect ively failed to improve with an atypical antipsychotic , clozapine was more effective than switching to another newer atypical antipsychotic . Safety monitoring is necessary to detect and manage clozapine 's serious side effects The data for medical decision analyses are often unreliable . Traditional sensitivity analysis --varying one or more probability or utility estimates from baseline values to see if the optimal strategy changes -- is cumbersome if more than two values are allowed to vary concurrently . This paper describes a practical method for probabilistic sensitivity analysis , in which uncertainties in all values are considered simultaneously . The uncertainty in each probability and utility is assumed to possess a probability distribution . For ease of application we have used a parametric model that permits each distribution to be specified by two values : the baseline estimate and a bound ( upper or lower ) of the 95 percent confidence interval . Following multiple simulations of the decision tree in which each probability and utility is r and omly assigned a value within its distribution , the following results are recorded : ( a ) the mean and st and ard deviation of the expected utility of each strategy ; ( b ) the frequency with which each strategy is optimal ; ( c ) the frequency with which each strategy " buys " or " costs " a specified amount of utility relative to the remaining strategies . As illustrated by an application to a previously published decision analysis , this technique is easy to use and can be a valuable addition to the armamentarium of the decision analyst We examined the response to clozapine in 10 schizophrenic patients who had been followed prospect ively from the time of their first hospitalization and who were refractory to multiple clinical trials with typical Clozapine is the only antipsychotic in the United States that has been approved by the Food and Drug Administration ( FDA ) for treatment-resistant schizophrenia . It provides effective treatment even when patients do not respond to other secondgeneration antipsychotics . [ 1 ] It also remains the most effective antipsychotic available . No existing first or second-generation antipsychotic has been consistently found to be as effective as clozapine monotherapy in treatment-resistant patients . [ 2 - 6 ] Among patients who entered Phase 2 of the Clinical Antipsychotic Trial of Intervention Effectiveness ( CATIE ) because of lack of efficacy in Phase 1 of the study , those treated with clozapine ( open label ) averaged significantly greater time to treatment discontinuation ( 10.5 months ) compared to patients treated with other antipsychotic medications ( 2.7 - 3.3 months ) . At three months , total symptom scores also improved to a significantly greater degree in the clozapine group compared to those treated with risperidone or quetiapine . [ 7 ] Similarly , in the open-label , r and omized CUtLASS ( Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study ) trial , clozapine treatment was associated with significantly greater improvement in total scores of the Positive and Negative Symptom Scale ( PANSS ) and better patient subjective ratings compared to risperidone , olanzapine , quetiapine , and amisulpiride . [ 8 ] Another large , nonr and omized effectiveness study , the Schizophrenia Outpatient Health Outcomes ( SOHO ) study , also found clozapine to be superior on clinician and patient ratings at six months compared to other antipsychotics . [ 9 ] Based on clinical trials , meta-analyses , and large naturalistic studies clozapine is recommended as the most effective agent in schizophrenia , but the recommendations indicate that it should only be used when other agents fail . [ 5 BACKGROUND Approximately 50 % of patients with schizophrenia or schizoaffective disorder attempt suicide , and approximately 10 % die of suicide . Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients . METHODS A multicenter , r and omized , international , 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder , 26.8 % of whom were refractory to previous treatment , who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation . To equalize clinical contact across treatments , all patients were seen weekly for 6 months and then biweekly for 18 months . Subsequent to r and omization , unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts . Suicidal behavior was assessed at each visit . Primary end points included suicide attempts ( including those that led to death ) , hospitalizations to prevent suicide , and a rating of " much worsening of suicidality " from baseline . Masked raters , including an independent suicide monitoring board , determined when end point criteria were achieved . RESULTS Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine ( hazard ratio , 0.76 ; 95 % confidence interval , 0.58 - 0.97 ; P = .03 ) . Fewer clozapine-treated patients attempted suicide ( 34 vs 55 ; P = .03 ) , required hospitalizations ( 82 vs 107 ; P = .05 ) or rescue interventions ( 118 vs 155 ; P = .01 ) to prevent suicide , or required concomitant treatment with antidepressants ( 221 vs 258 ; P = .01 ) or anxiolytics or soporifics ( 301 vs 331 ; P = .03 ) . Overall , few of these high-risk patients died of suicide during the study ( 5 clozapine vs 3 olanzapine-treated patients ; P = .73 ) . CONCLUSIONS Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide . Use of clozapine in this population should lead to a significant reduction in suicidal behavior BACKGROUND Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia , questions remain regarding its efficacy for primary negative symptoms , comparison with a moderate dose of a first-generation antipsychotic , and adverse effects during a longer-term trial . This study examined its efficacy in partially responsive , community-based patients , compared clozapine with moderate-dose haloperidol , and extended treatment to 6 months . METHODS R and omized , double-blind , 29-week trial comparing clozapine ( n = 37 ) with haloperidol ( n = 34 ) . Subjects with schizophrenia who were being treated in community setting s at 3 collaborating clinical facilities were enrolled . RESULTS Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy ( 51 % ) than were those treated with clozapine ( 12 % ) . A higher proportion of clozapine-treated subjects met an a priori criterion of improvement ( 57 % ) compared with haloperidol-treated subjects ( 25 % ) . Significantly greater improvement was seen in symptoms of psychosis , hostile-suspiciousness , anxiety-depression , thought disturbance , and total score measured on the Brief Psychiatric Rating Scale . No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms . Subjects treated with clozapine experienced more excess salivation , dizziness , and sweating and less dry mouth and decreased appetite than those treated with haloperidol . CONCLUSIONS Compared with a first-generation antipsychotic given in a moderate dose , clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community . Advantages are seen in a broad range of symptoms but do not extend to negative symptoms This study compared the time course to clinical improvement with clozapine and with conventional antipsychotic medications . A double-blind trial compared clozapine and haloperidol in patients with schizophrenia who were refractory to conventional antipsychotic medication and were hospitalized for 30 to 364 days at 15 Veteran Affairs medical centers during the year before study entry . Patients in the original study were r and omly assigned to haloperidol or clozapine and followed for 12 months , at maximum tolerable doses . Patients who completed a full year of treatment with clozapine ( n = 122 ) , or with either haloperidol or another conventional antipsychotic medication ( n = 123 ) and who also completed the 9- or 12-month assessment were included . Response to treatment was defined as 20 percent improvement on st and ard scales of symptoms and quality of life at the latter of the 9- or 12-month interviews . More patients assigned to clozapine achieved 20 percent improvement in symptoms at each followup . Among patients who did not improve at 6 weeks , 3 months , or 6 months , there were no significant differences between clozapine and comparison patients in outcomes at 1 year . Among patients who did improve , maintenance of that improvement also did not differ between the groups at 1 year on symptom measures . Maintenance of improvement in quality of life at 1 year was significantly greater for clozapine patients who had improved at 6 months ( p < 0.04 ) . Significant differential symptom response to clozapine occurred exclusively during the first 6 weeks of treatment BACKGROUND Despite the advent of new atypical antipsychotics , clozapine remains an important option in the treatment of patients with poor response to conventional antipsychotics . Clinicians would be well served if clinical characteristics could be identified that predict a favorable response to clozapine . A few studies addressing this issue have reported inconsistent results . METHOD The association of clinical characteristics with a sustained response was investigated in 37 partially treatment-refractory out patients with a DSM-III-R diagnosis of chronic schizophrenia who had been assigned to clozapine treatment in a double-blind , haloperidol-controlled , long-term ( 29-week ) study of clozapine . Response was defined as a 20 % decrease of the Brief Psychiatric Rating Scale ( BPRS ) psychosis factor score sustained over 2 consecutive ratings . Differences between responders and nonresponders with regard to selected baseline variables were analyzed with t tests and chi2 tests . In addition , Cox regression analyses were performed to identify variables that best predicted a response to clozapine treatment . RESULTS Clozapine responders were rated as less severely ill , showed a lesser degree of negative symptoms , and demonstrated fewer extrapyramidal side effects at baseline as compared with nonresponders . In addition , higher BPRS total scores -- after controlling for the effects of the other variables -- were associated with a response . CONCLUSION In a cohort of partially treatment-refractory out patients , a favorable response to clozapine was associated with characteristics describing less severely ill patients . The history of patients did not affect their response to clozapine The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics . DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospect i ve , single-blind trial of haloperidol ( mean dosage , 61 + /- 14 mg/d ) for six weeks . Patients whose condition remained unimproved were then r and omly assigned , in a double-blind manner , to clozapine ( up to 900 mg/d ) or chlorpromazine ( up to 1800 mg/d ) for six weeks . Two hundred sixty-eight patients were entered in the double-blind comparison . When a priori criteria were used , 30 % of the clozapine-treated patients were categorized as responders compared with 4 % of chlorpromazine-treated patients . Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale , Clinical Global Impression Scale , and Nurses ' Observation Scale for Inpatient Evaluation ; this improvement included " negative " as well as positive symptom areas . Although no cases of agranulocytosis occurred during this relatively brief study , in our view , the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients BACKGROUND Clozapine , a relatively expensive antipsychotic drug , is widely used to treat patients with refractory schizophrenia . It has a low incidence of extrapyramidal side effects but may cause agranulocytosis . There have been no long-term assessment s of its effect on symptoms , social functioning , and the use and cost of health care . METHODS We conducted a r and omized , one-year , double-blind comparative study of clozapine ( in 205 patients ) and haloperidol ( in 218 patients ) at 15 Veterans Affairs medical centers . All participants had refractory schizophrenia and had been hospitalized for the disease for 30 to 364 days in the previous year . All patients received case-management and social-rehabilitation services , as clinical ly indicated . RESULTS In the clozapine group , 117 patients ( 57 percent ) continued their assigned treatment for the entire year , as compared with 61 ( 28 percent ) of the patients in the haloperidol group ( P<0.001 ) . As judged according to the Positive and Negative Syndrome Scale of Schizophrenia , patients in the clozapine group had 5.4 percent lower symptom levels than those in the haloperidol group at all follow-up evaluations ( mean score , 79.1 vs. 83.6 ; P=0.02 ) . The differences on a quality -of-life scale were not significant in the intention-to-treat analysis , but they were significant among patients who did not cross over to the other treatment ( P=0.003 ) . Over a one-year period , patients assigned to clozapine had fewer mean days of hospitalization for psychiatric reasons than patients assigned to haloperidol ( 143.8 vs. 168.1 days , P=0.03 ) and used more outpatient services ( 133.6 vs. 97.9 units of service , P=0.03 ) . The total per capita costs to society were high -- $ 58,151 in the clozapine group and $ 60,885 in the haloperidol group ( P=0.41 ) . The per capita costs of antipsychotic drugs were $ 3,199 in the clozapine group and $ 367 in the haloperidol group ( P<0.001 ) . Patients assigned to clozapine had less tardive dyskinesia and fewer extrapyramidal side effects . Agranulocytosis developed in three patients in the clozapine group ; all recovered fully . CONCLUSIONS For patients with refractory schizophrenia and high levels of hospital use , clozapine was somewhat more effective than haloperidol and had fewer side effects and similar overall costs BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism OBJECTIVE This study sought to determine the relationships between serum clozapine levels and therapeutic response . METHOD Fifty-six in patients who met the DSM-III-R criteria for chronic schizophrenia and who had not responded to extended treatment with classical antipsychotics were r and omly assigned to 12 weeks of double-blind treatment with clozapine at one of three serum level ranges : low ( 50 - 150 ng/ml ) , medium ( 200 - 300 ng/ml ) , or high ( 350 - 450 ng/ml ) . Baseline clinical assessment s were completed before the patients ' regular antipsychotic and anticholinergic drugs were discontinued . During clozapine treatment , serum levels were ascertained weekly to allow adjustment of clozapine doses so as to maintain each patient near the midpoint of his or her assigned serum level range . Clinical assessment s were completed after 6 and 12 weeks of treatment . RESULTS The analyses of the results of treatment supported the superior efficacy of the 200 - 300 ng/ml and 350 - 450 ng/ml serum clozapine level ranges over the 50 - 150 ng/ml range , with no advantage for 350 - 450 ng/ml over 200 - 300 ng/ml . Sleepiness increased with increasing serum levels . CONCLUSIONS Serum clozapine levels per unit of daily dose were at the lower end of the range noted in previous reports , possibly reflecting the current study 's dosing schedules of twice or three times a day , the 11- to 13-hour postdose sampling time , and the moderate doses given . Serum clozapine levels , if interpreted in relation to daily clozapine dosing schedules , postdose sampling time , and total daily dose , may help to guide dosing to provide adequate opportunities for therapeutic response and to limit certain side effects of clozapine treatment OBJECTIVE This study explored the relative efficacy of three different doses of clozapine . METHOD Fifty patients who met Kane et al. 's criteria for treatment-refractory schizophrenia or schizoaffective disorder were studied . All subjects were r and omly assigned to 100 , 300 , or 600 mg/day of clozapine for 16 weeks of double-blind treatment . Forty-eight patients completed this first 16 weeks . Of the 50 patients , 36 went on to second and third 16-week trials of double-blind treatment at the remaining doses . RESULTS Four subjects ( 8 % ) responded to the first 16-week condition , and one subject ( 2 % ) responded to the next 16-week crossover condition . A chi-square comparison of the response rates from the three dose groups failed to show a significant effect . An analysis of variance ( ANOVA ) comparison of Brief Psychiatric Rating Scale-Anchored ( BPRS-A ) total change scores from baseline to last observation carried forward showed a significant dose effect ( 600>300>100 mg/day ) at 16 weeks of treatment . A crossover ANOVA of the BPRS-A total scores from the 48-week study also showed that the main effect for dose was highly significant ; the 100-mg/day dose gave the higher ( poorer ) values , and the 300- and 600-mg/ day doses gave equal ( better ) values . Gender played a role in clinical response to treatment at 100 mg/day . CONCLUSIONS Clozapine treatment at 100 mg/day was less effective than at 300 or 600 mg/day . At 100 mg/day , women responded better than did men . The 600 mg/day group had the best results , but an occasional patient required up to 900 mg/day . Overall response rates were lower than expected 1 . The atypical antipsychotic risperidone may constitute an alternative to clozapine , the current treatment of choice for refractory schizophrenia . The objectives of this study were to evaluate the effectiveness of risperidone in comparison to clozapine in everyday practice and to assess the feasibility of a pragmatic trial procedure . 2 . Patients were r and omly assigned to open-label clozapine or risperidone treatment for 10 weeks and treatment outcomes were assessed blindly . Twenty-one patients were recruited and nineteen entered the r and omized phase . 3 . Five of 10 participants allocated to clozapine and one of nine risperidone participants dropped out before study completion . Five clozapine patients and six risperidone patients achieved clinical improvement , defined as a 20 % decrease in the Positive and Negative Symptom Scale ( PANSS ) total score . No significant differences between the groups were detected in baseline or endpoint positive or negative symptoms , disease severity , or global or social functioning scores . Patients ' opinion on the drugs did not differ between groups . 4 . The findings of the intention-to-treat analysis of this study corroborates previous findings that risperidone may be equally effective as clozapine , and supports the feasibility and need of a multicenter r and omized pragmatic trial with sufficient power to detect differences between treatments OBJECTIVE Clozapine is the only compound proven to be effective in the 20 % of schizophrenic patients refractory to treatment with conventional neuroleptics . Although its mechanism of action has not been eluci date d , clozapine appears , in contrast to most conventional neuroleptics , to be a potent serotonin ( 5-HT ) antagonist . This study hypothesized that 5-HT function is increased in patients who benefit from clozapine treatment relative to patients who fail to improve on it . METHOD The 5-HT receptor agonist m-chlorophenylpiperazine ( MCPP ) was used as a probe to examine 5-HT function . MCPP ( 0.35 mg/kg p.o . ) was administered in a placebo-controlled design after a 3-week drug-free period to 19 schizophrenic patients . ACTH , prolactin , body temperature , behavior , and MCPP blood level were measured . Patients were then treated with a conventional neuroleptic , and , having failed to respond to it , were treated with clozapine for 5 weeks ( up to 600 mg/day ) . RESULTS Patients who responded to clozapine had significantly higher ACTH responses to MCPP during the drug-free state than the patients who failed to benefit from clozapine . Moreover , the degree of improvement with clozapine , particularly the improvement in psychotic symptoms , was strongly correlated with the magnitude of MCPP-induced ACTH release . Other MCPP-induced responses and MCPP blood level were similar for the two groups and did not correlate with the degree of symptomatic improvement with clozapine . CONCLUSIONS Results of this study suggest that MCPP-induced ACTH release , and by inference 5-HT receptor function , may be increased in patients who benefit from treatment with clozapine relative to patients who fail to improve on this drug OBJECTIVE The authors sought to determine the time to clozapine response in treatment-refractory patients with schizophrenia . METHOD Antipsychotic response to a clozapine trial was examined in 50 treatment-refractory schizophrenic in patients . Subjects were treated with clozapine for at least 12 months , regardless of response status , according to a st and ardized , increasing dose protocol . Behavioral changes were measured through monthly assessment s with the Brief Psychiatric Rating Scale . RESULTS Thirty-four subjects ( 68 % ) met clinical response criteria by the end of the trial . Response was achieved at a mean dose of 468 mg/day ( SD = 168 ) . The dose of 30 ( 88 % ) of the responding patients was 600 mg/day or less . The mean time to response was 82 days ( SD = 100 , range = 10 - 401 ) . It took an average of 60 days ( SD = 87 ) for subjects to reach the dose at which clozapine response was achieved . Once this dose was reached , the average response time was 17 days ( SD = 14 , range = 2 - 56 ) . All 34 subjects who responded met criteria within 8 weeks of a clozapine dose escalation . No late response was found in the remaining 16 subjects despite a mean follow-up period of 75 weeks ( SD = 50 ) . CONCLUSIONS In this study , all patients who responded to clozapine did so within 8 weeks of a change in dose . Thus , there appears to be little clinical gain in prolonging exposure to clozapine beyond 8 weeks at any particular dose if no response is seen Objective To study the clinical response to clozapine in patients with refractory schizophrenia . Method Open trial of clozapine in 61 consecutively-treated patients . Results Following clozapine , the level of function of patients was improved relative to admission ( p = 0.0001 ) and to the highest level in the previous year ( p = 0.0001 ) . Severity of illness was decreased ( p = 0.0001 ) . Overall , 31 % of the patients were classified as responders to clozapine and the responders were all identified by 32 weeks of treatment . Poor functioning in the previous year was associated with less favourable response . At a mean interval of 26 months following discharge , 72 % of the patients were continuing clozapine treatment . Conclusions This open trial of patients who were treated consecutively indicates a comparable degree of response to clozapine as observed in controlled clinical trials , and that level of functioning in the previous year was the best predictor of response Thirty-eight chronically ill psychotic patients were treated with clozapine for indications of tardive dyskinesia , severe extrapyramidal side effects caused by other neuroleptics , or treatment-resistant psychosis . Fifty-five percent of all patients and 40 % of schizophrenics improved with clozapine . Abnormal involuntary movements were suppressed during treatment and , with 1 exception , returned to baseline levels after clozapine was discontinued . Our results support the conclusion that clozapine 's efficacy in refractory cases and its lack of neurological side effects make it a unique neuroleptic with advantages over conventional antipsychotic agents . The drug appears to be safe when treatment is accompanied by frequent clinical and hematologic monitoring OBJECTIVE The purpose of the study was to examine the effects of clozapine in treating moderately ill schizophrenic out patients and to determine the length of medication trial needed to identify responders and nonresponders . METHODS Rates of clinical responses , relapses and hospitalizations , and levels of symptomatology and functioning were assessed for 30 chronic schizophrenic out patients who received clozapine for one year . For some patients , data on relapse and hospitalization during treatment were compared with data from the year before treatment . RESULTS Eighteen of the 30 patients met criteria for sustained response ; 17 of the responders were identified within the first four months of treatment . Patients experienced significantly fewer relapses and hospitalizations during treatment than in the previous year . Improvement in positive symptoms , general symptomatology , and levels of functioning reached a plateau during the first six months of treatment and remained at that level during the second six months . Negative symptoms and quality of life showed nonsignificant improvements at 12 months . CONCLUSIONS Results support the use of clozapine in treating chronic , residually symptomatic schizophrenic out patients . A four-month clozapine trial may be adequate to detect clinical responders in this population BACKGROUND Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia ( TRS ) . However , clinicians appear to be hesitant to prescribe this drug . It would therefore be extremely valuable if predictors of response to clozapine could be identified . The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS . METHODS This was a 16-week uncontrolled open study carried out among 97 TRS patients ( 80 males and 17 females ; DSM-IV diagnosis ) . All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence ( NICE ) . After all previous antipsychotic medications had run their course , the patients were started on clozapine according to a st and ardized titration and dosage schedule . Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale ( BPRS ) , the Scale for the Assessment for Positive Symptoms , and the Scale for the Assessment of Negative Symptoms . RESULTS Of the TRS patients on clozapine , 55.7 % achieved a clinical response , defined as at least a 20 % decrease in BPRS . We observed a favorable effect of clozapine on both positive and negative symptoms . Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age , when negative symptoms were severe , and when patients had an early response at 4 weeks . CONCLUSION A combination of demographic , baseline clinical , and acute treatment response variables may accurately predict response to clozapine in TRS . Priority should be given to initiating clozapine at the earliest phase of TRS , especially for patients with evident negative symptoms There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia . It is less clear if clozapine is more effective than the other second-generation antipsychotic ( SGA ) drugs . A noncommercially funded , pragmatic , open , multisite , r and omized controlled trial was conducted in the United Kingdom National Health Service ( NHS ) . Participants were 136 people aged 18 - 65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs . Participants were r and omly allocated to clozapine or to one of the class of other SGA drugs ( risperidone , olanzapine , quetiapine , amisulpride ) as selected by the managing clinician . Outcomes were assessed blind to treatment allocation . One-year assessment s were carried out in 87 % of the sample . The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score ( 3.63 points ; CI : 0.46 - 7.71 ; p = .08 ) but did show an advantage in Positive and Negative Syndrome Scale ( PANSS ) total score that was statistically significant ( -4.93 points ; CI : -8.82 to -1.05 ; p = .013 ) during follow-up . Clozapine showed a trend toward having fewer total extrapyramidal side effects . At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs . In conclusion , in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs , there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year Abstract : The subjects were 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week , double-blind trial . Incidents of overt aggression were recorded and their severity was scored . The Positive and Negative Syndrome Scale was administered . Atypical antipsychotics showed an overall superiority over haloperidol , particularly after the first 24 days of the study when the dose escalation of clozapine was completed . Once an adequate therapeutic dose of clozapine was reached , it was superior to haloperidol in reducing the number and severity of aggressive incidents . Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients . There was an interaction between aggressiveness , medication type , and antipsychotic response : risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior ; the opposite was true for clozapine . Clozapine appears to have superior antiaggresive effects in treatment-resistant patients ; this superiority develops after the patient has been exposed to an adequate dose regimen Clozapine is a novel antipsychotic agent that selectively blocks mesolimbic -- rather than nigrostriatal -- dopamine receptors , causes fewer extrapyramidal symptoms than do other neuroleptics , and has superior antipsychotic efficacy in some patients . However , clozapine also causes agranulocytosis more frequently than do other neuroleptics . The evidence documenting the superior benefits obtained with clozapine has primarily involved short-term ( 4 - 6 weeks ) trials , and the systematic evaluation of long-term clozapine use has been limited . In this study , 14 patients with refractory chronic schizophrenia were treated openly with clozapine up to 2 years ; 8 did substantially better when given clozapine than they had when given other neuroleptics . That finding suggests that clozapine may provide a useful addition to the therapeutic armamentarium for the long-term treatment of schizophrenia , despite the increased risks and the need for frequent blood tests |
2,134 | 22,081,614 | Overall , daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods ( β-carotene , vitamins C and E ) and folate .
Functional changes , such as reduced serum homocysteine and markers of protein , lipid , and DNA oxidation , were also reported ; in addition , the health advantages on markers of inflammation , immunity , and endothelial function are promising .
Key teaching points : Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables .
Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins ( β-carotene , vitamins C and E ) and folate and reduce homocysteine and markers of oxidative stress . | Diets rich in fruits and vegetables ( FV ) have been associated with a reduced risk of chronic disease , including cardiovascular disease .
Unfortunately , public health campaigns to increase FV intake have had limited success .
A number of mixed concentrated FV products have been studied , which may help certain individuals improve nutrient status .
However , the possible health benefits of FV supplements have not been systematic ally review ed .
We , therefore , undertook a systematic search of MEDLINE and EMBASE to identify clinical interventions that examined the effect of commercially available concentrated mixed FV supplements on cardiovascular disease risk factors . | CONTEXT To enhance the effectiveness of diet in lowering cholesterol , recommendations of the Adult Treatment Panel III of the National Cholesterol Education Program emphasize diets low in saturated fat together with plant sterols and viscous fibers , and the American Heart Association supports the use of soy protein and nuts . OBJECTIVE To determine whether a diet containing all of these recommended food components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . DESIGN R and omized controlled trial conducted between October and December 2002 . SETTING AND PARTICIPANTS Forty-six healthy , hyperlipidemic adults ( 25 men and 21 postmenopausal women ) with a mean ( SE ) age of 59 ( 1 ) years and body mass index of 27.6 ( 0.5 ) , recruited from a Canadian hospital-affiliated nutrition research center and the community . INTERVENTIONS Participants were r and omly assigned to undergo 1 of 3 interventions on an outpatient basis for 1 month : a diet very low in saturated fat , based on milled whole-wheat cereals and low-fat dairy foods ( n = 16 ; control ) ; the same diet plus lovastatin , 20 mg/d ( n = 14 ) ; or a diet high in plant sterols ( 1.0 g/1000 kcal ) , soy protein ( 21.4 g/1000 kcal ) , viscous fibers ( 9.8 g/1000 kcal ) , and almonds ( 14 g/1000 kcal ) ( n = 16 ; dietary portfolio ) . MAIN OUTCOME MEASURES Lipid and C-reactive protein levels , obtained from fasting blood sample s ; blood pressure ; and body weight ; measured at weeks 0 , 2 , and 4 and compared among the 3 treatment groups . RESULTS The control , statin , and dietary portfolio groups had mean ( SE ) decreases in low-density lipoprotein cholesterol of 8.0 % ( 2.1 % ) ( P = .002 ) , 30.9 % ( 3.6 % ) ( P<.001 ) , and 28.6 % ( 3.2 % ) ( P<.001 ) , respectively . Respective reductions in C-reactive protein were 10.0 % ( 8.6 % ) ( P = .27 ) , 33.3 % ( 8.3 % ) ( P = .002 ) , and 28.2 % ( 10.8 % ) ( P = .02 ) . The significant reductions in the statin and dietary portfolio groups were all significantly different from changes in the control group . There were no significant differences in efficacy between the statin and dietary portfolio treatments . CONCLUSION In this study , diversifying cholesterol-lowering components in the same dietary portfolio increased the effectiveness of diet as a treatment of hypercholesterolemia The daily consumption of fruits and vegetables is a common dietary recommendation to support good health . We hypothesized that a commercially available encapsulated fruit and vegetable juice powder concentrate ( FVJC ) could support functional indices of health due to increased intake of various phytonutrients . This was a double-blind , r and omized , placebo-controlled investigation of 59 healthy law students who consumed either FVJC or placebo capsules for 77 d. Blood was collected on d 1 , 35 , and 77 to examine the number of circulating alphabeta- and gammadelta-T cells , cytokine production , lymphocyte DNA damage , antioxidant status , and levels of carotenoids and vitamin C. A log of illnesses and symptoms was also kept . The FVJC group tended to have fewer total symptoms than the placebo group ( P < 0.076 ) . By d 77 there was a 30 % increase in circulating gammadelta-T cells and a 40 % reduction in DNA damage in lymphocytes in the FVJC group relative to the placebo group . Plasma levels of vitamin C and of beta-carotene , lycopene , and lutein increased significantly from baseline in the FVJC group as did plasma oxygen radical absorptive capacity ( 50 % ) . Interferon-gamma produced by phorbol-stimulated lymphocytes was reduced 70 % in the FVJC group , whereas other cytokines ( IL-4 , IL-6 , transforming growth factor beta ) were unchanged relative to treatment or time . FVJC consumption during this study period result ed in increased plasma nutrients and antioxidant capacity , reduction in DNA str and breaks , and an increase in circulating gammadelta-T cells Phytonutrients from plant foods provide numerous antioxidants . We hypothesized that supplementation for 28 wk with a commercially available encapsulated juice powder concentrate ( JPC ) could influence indicators of oxidative stress , immunity , and illness . Trained men ( n = 41 ; 34 + /- 5 y ; maximum oxygen uptake = 55 + /- 7 mL x kg(-1 ) x min(-1 ) ) from a homogenous police Special Forces unit were r and omly assigned in a double blind manner to either JPC ( n = 21 ) or placebo ( n = 20 ) . We used multiple 7-d food records to assess dietary intake and found inadequate mean daily fruit and vegetable consumption ( 3.2 + /- 1.2 servings ) . The group physician documented all duty days lost due to illness . We collected plasma at baseline and study wk 4 , 8 , 16 , and 28 for analysis of carbonyl groups on protein ( CP ) and TNFalpha . Over the 28-wk investigation , CP was lower in the JPC group , with both a treatment and a time x treatment interaction ( P < 0.05 ) . Concentrations of both CP and TNFalpha at 16 and 28 wk were lower in the JPC than in the placebo group ( P < 0.001 ) . TNFalpha increased during the first 8 wk followed by a decrease in both groups for the following 20 wk ( P < 0.001 ) . Over the final 20 wk of the study , the placebo group tended to have more days of illness than the JPC group ( P = 0.068 ) . These data suggest beneficial JPC effects with regard to reduction of duty days lost due to illness and reduction of CP and TNFalpha concentrations in this group of trained men over 28 wk Fruit and vegetable consumption is inversely associated with coronary heart disease ( CHD ) risk . The aim of the present study was to determine the effect of supplementation with dehydrated juice concentrates from mixed fruit and vegetables on selected plasma vitamins and antioxidant status . We assessed CHD risk by measuring the concentrations of homocysteine , lipids , lipoproteins , glucose and insulin . Men were recruited to participate in a r and omized double-blind , crossover trial with 2 periods of 6 wk , separated by a 3-wk wash-out period . Supplementation with the encapsulated mixed extract ( Juice Plus ) was compared with physically similar placebo capsules . Thirty-two men ( 13 smokers , 19 nonsmokers ) completed the study with a mean compliance of 88 % . Compared with placebo , supplementation increased the concentrations of plasma beta-carotene ( 0.24 + /- 0.15 vs. 1.12 + /- 0.70 micro mol/L ; mean + /- SD ; P < 0.0001 ) , retinol ( 1.87 + /- 0.33 vs. 2.00 + /- 0.43 micro mol/L ; P < 0.05 ) , alpha-tocopherol ( 16.8 + /- 7.3 vs. 19.3 + /- 6.8 micro mol/L ; P < 0.01 ) , ascorbic acid ( 72.1 + /- 19.4 vs. 84.1 + /- 13.5 micro mol/L ; P < 0.002 ) and folic acid ( 24.5 + /- 10.0 vs. 44.9 + /- 16.9 nmol/L ; P < 0.0001 ) . Plasma homocysteine was reduced ( 8.2 + /- 1.5 vs. 7.6 + /- 1.1 ; P < 0.05 ) and inversely related ( r = -0.40 , P < 0.001 ) with serum folate concentrations . Plasma vitamin C was positively correlated with the resistance of LDL to oxidation ( r = 0.26 , P < 0.05 ) and the plasma ferric reducing/antioxidant power ( FRAP ) tended to be greater after supplementation than after the placebo period ( 1125.5 + /- 144.1 vs. 1180.3 + /- 158.1 micro mol/L ; P < 0.065 ) . Plasma glucose , insulin and lipid concentrations were unaffected . Responses of smokers and nonsmokers did not differ . In the absence of dietary modification , supplementation with a fruit and vegetable concentrate produced responses consistent with a reduction in CHD risk OBJECTIVES Our objective was to determine if long-term daily administration of phytonutrient supplements can prevent the immediate adverse impact of a high-fat meal and increase the production of nitric oxide . BACKGROUND Ingestion of a high-fat meal impairs flow-mediated vasodilation of the brachial artery for at least 4 h ; however , co-ingestion of vitamin antioxidants or a green salad has been shown to prevent this effect . METHODS Flow-mediated brachial artery reactivity test ( BART ) both before and 3 h after a 900 calorie 50 g fat meal was evaluated in 38 healthy volunteers ( age 36.4 + /- 10.1 years ) . Subjects were r and omized to four weeks of daily supplementation with a powdered fruit vegetable juice concentrate ( Juice Plus [ JP ] ) along with a complex supplement providing nutritional antioxidants and various herbal extracts ( Vineyard [ V ] ) , JP alone , or a matching placebo . At three and four weeks , BART was repeated both before and after the high-fat meal . Serum nitrate/nitrite concentrations were measured at baseline and at four weeks . RESULTS Four weeks of the JP-V combination blunted the detrimental effect of the high-fat meal ( -47.5 + /- 23.4 % at baseline vs. -1.7 + /- 9.7 % at four weeks [ p < 0.05 ] ) . Four weeks of JP alone had a similar beneficial effect ( -45.1 + /- 19.7 % at baseline vs. -16.6 + /- 10.3 % at four weeks [ p < 0.05 ] ) , whereas there was no substantial effect of the placebo . In the subjects treated with supplements , concentrations of serum nitrate/nitrite increased from 78 + /- 39 to 114 + /- 62 microm/l ( p < 0.02 ) . CONCLUSIONS Daily ingestion of modest amounts of a fruit/vegetable juice concentrate with or without adjunctive phytonutrient supplementation can reduce the immediate adverse impact of high-fat meals on flow-mediated vasoactivity and increase nitrate/nitrite blood concentration Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease , diabetes , and cancer . A high " inflammatory load " is defined as elevated inflammation markers in blood or other tissues . We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders ( FVB ) or without ( FV ) could impact markers of inflammatory load . Using a double-blind , placebo-controlled approach , 117 subjects were r and omly assigned to receive placebo , FV , or FVB capsules . Blood was drawn at baseline and after 60 d of capsule consumption . We measured inflammatory markers ( high sensitivity C-Reactive Protein , Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and Regulated upon Activation , Normal T cell Expressed and Secreted ) , superoxide dismutase , and micronutrients ( β-carotene , vitamin C , and vitamin E ) . Results showed Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB , relative to placebo . Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti-inflammatory properties BACKGROUND Studies of fruit and vegetable consumption in relation to overall health are limited . We evaluated the relationship between fruit and vegetable intake and the incidence of cardiovascular disease and cancer and of deaths from other causes in two prospect i ve cohorts . METHODS A total of 71 910 female participants in the Nurses ' Health study and 37,725 male participants in the Health Professionals ' Follow-up Study who were free of major chronic disease completed baseline semiquantitative food-frequency question naires in 1984 and 1986 , respectively . Dietary information was up date d in 1986 , 1990 , and 1994 for women and in 1990 and 1994 for men . Participants were followed up for incidence of cardiovascular disease , cancer , or death through May 1998 ( women ) and January 1998 ( men ) . Multivariable-adjusted relative risks were calculated with Cox proportional hazards analysis . RESULTS We ascertained 9329 events ( 1964 cardiovascular , 6584 cancer , and 781 other deaths ) in women and 4957 events ( 1670 cardiovascular diseases , 2500 cancers , and 787 other deaths ) in men during follow-up . For men and women combined , participants in the highest quintile of total fruit and vegetable intake had a relative risk for major chronic disease of 0.95 ( 95 % confidence interval [ CI ] = 0.89 to 1.01 ) times that of those in the lowest . Total fruit and vegetable intake was inversely associated with risk of cardiovascular disease but not with overall cancer incidence , with relative risk for an increment of five servings daily of 0.88 ( 95 % CI = 0.81 to 0.95 ) for cardiovascular disease and 1.00 ( 95 % CI = 0.95 to 1.05 ) for cancer . Of the food groups analyzed , green leafy vegetable intake showed the strongest inverse association with major chronic disease and cardiovascular disease . For an increment of one serving per day of green leafy vegetables , relative risks were 0.95 ( 95 % CI = 0.92 to 0.99 ) for major chronic disease and 0.89 ( 95 % CI = 0.83 to 0.96 ) for cardiovascular disease . CONCLUSIONS Increased fruit and vegetable consumption was associated with a modest although not statistically significant reduction in the development of major chronic disease . The benefits appeared to be primarily for cardiovascular disease and not for cancer Background Prospect i ve cohort studies have shown that high fruit and vegetable consumption is inversely associated with coronary heart disease ( CHD ) . Whether food processing affects this association is unknown . Therefore , we quantified the association of fruit and vegetable consumption with 10-year CHD incidence in a population -based study in the Netherl and s and the effect of processing on these associations . Methods Prospect i ve population -based cohort study , including 20,069 men and women aged 20 to 65 years , enrolled between 1993 and 1997 and free of cardiovascular disease at baseline . Diet was assessed using a vali date d 178-item food frequency question naire . Hazard ratios ( HR ) were calculated for CHD incidence using multivariable Cox proportional hazards models . Results During a mean follow-up time of 10.5y , 245 incident cases of CHD were documented , which comprised 211 non-fatal acute myocardial infa rct ions and 34 fatal CHD events . The risk of CHD incidence was 34 % lower for participants with a high intake of total fruit and vegetables ( > 475 g/d ; HR : 0.66 ; 95 % CI : 0.45–0.99 ) compared to participants with a low total fruit and vegetable consumption ( ≤241 g/d ) . Intake of raw fruit and vegetables ( > 262 g/d vs ≤92 g/d ; HR : 0.70 ; 95 % CI : 0.47–1.04 ) as well as processed fruit and vegetables ( > 234 g/d vs ≤113 g/d ; HR : 0.79 ; 95 % CI : 0.54–1.16 ) were inversely related with CHD incidence . Conclusion Higher consumption of fruit and vegetables , whether consumed raw or processed , may protect against CHD incidence Abstract Background : Cigarette smoking , a cardiovascular risk factor leading to oxygen free radical formation , is involved in the development of serious pathological conditions . On the other h and , a healthy diet and adequate supplementation can help prevent many diseases . The aim of our study was to evaluate in healthy light smokers the effects of supplementation with mixed fruit and vegetable juice powder concentrate on homocysteine metabolism and oxidative status . Methods : In this pilot study , 32 healthy volunteers , 16 light smokers and 16 non-smokers , on twice daily supplementation were monitored at time zero and after 30days . Plasma homocysteine , and serum vitamin B12 and folate concentrations were measured by immunoenzymatic assays ; reactive oxygen species , total antioxidant capacity and thiol groups by spectrophotometric methods ; and total and free malondialdehyde concentrations by gas chromatography-mass spectrometry with isotopic dilution . Results : Baseline free malondialdehyde concentrations were significantly higher in smokers than in non-smokers and normalised after 30-day supplementation . Baseline results for all the other parameters remained unchanged after supplementation , with no significant differences between smokers and non-smokers . Conclusion : This is the first study showing a significant decrease in free malondialdehyde levels in light smokers after 1-month phytonutrient supplementation Effective diets reduce blood lipids and oxidative damage , both of which have been linked to the complications of diabetes and coronary heart disease . Our objective was to assess the effect of adding strawberries , as a source of antioxidants , to improve the antioxidant effect of a cholesterol-lowering diet ( dietary portfolio ) . To this end , 28 hyperlipidemic subjects who had followed the dietary portfolio consisting of soy , viscous fiber , plant sterol , and nuts for a mean of 2.5 years were r and omized to receive supplements of strawberries ( 454 g/d , 112 kcal ) or additional oat bran bread ( 65 g/d , 112 kcal , approximately 2 g beta-glucan ) ( control ) in a r and omized 1-month crossover study with a 2-week washout . Strawberry supplementation result ed in a greater reduction in oxidative damage to low-density lipoprotein ( LDL ) measured as thiobarbituric acid-reactive substances in the LDL fraction ( P = .014 ) . At the end of the strawberry period , reductions in LDL cholesterol and in the ratio of total to high-density lipoprotein cholesterol were maintained close to 1-year values at -13.4 % + /- 2.1 % and -15.2 % + /- 1.7 % , respectively ( P < .001 ) , and were similar to the post-oat bran bread values . Strawberries also improved the palatability of the diet . We conclude that strawberry supplementation reduced oxidative damage to LDL while maintaining reductions in blood lipids and enhancing diet palatability . Added fruit may improve the overall utility of diets design ed to lower coronary heart disease risk Dietary supplements have been suggested in the prevention of the common cold , but previous investigations have been inconsistent . The present study was design ed to determine the preventive effect of a dietary supplement from fruits and vegetables on common cold symptoms . In a r and omised , double-blind , placebo-controlled trial , healthcare professionals ( mainly nursing staff aged 18–65 years ) from a university hospital in Berlin , Germany , were r and omised to four capsules of dietary supplement ( Juice Plus+ ® ) or matching placebo daily for 8 months , including a 2-month run-in period . The number of days with moderate or severe common cold symptoms within 6 months ( primary outcome ) was assessed by diary self-reports . We determined means and 95 % CI , and differences between the two groups were analysed by ANOVA . A total of 529 subjects were included into the primary analysis ( Juice Plus+ ® : 263 , placebo : 266 ) . The mean age of the participants was 39·9 ( sd 10·3 ) years , and 80 % of the participants were female . The mean number of days with moderate or severe common cold symptoms was 7·6 ( 95 % CI 6·5 , 8·8 ) in the Juice Plus+ ® group and 9·5 ( 8·4 , 10·6 ) in the placebo group ( P = 0·023 ) . The mean number of total days with any common cold symptoms was similar in the Juice Plus+ ® and in the placebo groups ( 29·4 ( 25·8 , 33·0 ) v. 30·7 ( 27·1 , 34·3 ) , P = 0·616 ) . Intake of a dietary supplement from fruits and vegetables was associated with a 20 % reduction of moderate or severe common cold symptom days in healthcare professionals particularly exposed to patient contact UNLABELLED Fruit and vegetable consumption has been inversely associated with the risk of chronic diseases including cancer and cardiovascular disease , with the beneficial effects attributed to a variety of protective antioxidants , carotenoids and phytonutrients . The objective of the present study was to determine the effect of supplementation with dehydrated concentrates from mixed fruit and vegetable juices ( Juice Plus+R ) on serum antioxidant and folate status , plasma homocysteine levels and markers for oxidative stress and DNA damage . Japanese subjects ( n=60 ; age 27.8 yrs ; BMI 22.1 ) were recruited to participate in a double-blind placebo controlled study and were r and omized into 2 groups of 30 , matched for sex , age , BMI and smoking status ( 39 males , 22 smokers ; 21 females , 13 smokers ) . Subjects were given encapsulated supplements containing mixed fruit and vegetable juice concentrates or a matching placebo for 28 days , with blood and urine sample s collected at baseline , day 14 and day 28 for analytical testing . Compared with the placebo , 28 day supplementation significantly increased the concentration of serum beta-carotene 528 % ( p<0.0001 ) , lycopene 80.2 % ( p<0.0005 ) , and alpha tocopherol 39.5 % ( p<0.0001 ) . Serum folate increased 174.3 % ( p<0.0001 ) and correlated with a decrease in plasma homocysteine of -19.9 % ( p<0.03 ) . Compared with baseline , measures of oxidative stress decreased with serum lipid peroxides declining -10.5 % ( p<0.02 ) and urine 8OHdG decreasing -21.1 % ( p<0.02 ) . Evaluation of data from smokers only ( n=17 ) after 28 days of active supplementation showed comparable changes . CONCLUSION In the absence of dietary modification , supplementation with the fruit and vegetable juice concentrate capsules proved to be a highly bioavailable source of phytonutrients . Important antioxidants were elevated to desirable levels associated with decreased risk of disease while markers of oxidative stress were reduced , and folate status improved with a concomitant decrease in homocysteine , and these benefits occurred to a similar extent in smokers when compared to non-smokers PURPOSE This study tested the effectiveness of a fruit , berry , and vegetable concentrate ( FVC ) , Juice Plus+ ® ( NSA LLC , Collierville , TN ) , supplement on muscle function and oxidative stress in response to an acute bout of eccentric exercise ( EE ) . METHODS Forty-one healthy volunteers ( age = 18 - 35 yr ) were r and omly assigned to either a placebo ( P ) or an FVC treatment taking capsules for 28 d ( 6 d(-1 ) ) before EE and for the next 4 d. All subjects completed four sets of 12 repetitions of eccentric elbow flexion with their nondominant arm . Blood , muscle soreness ( MS ) , range of motion ( ROM ) , and maximal isometric force ( MIF ) of the elbow flexors were obtained before and immediately after exercise and at 2 , 6 , 24 , 48 , and 72 h postexercise . Plasma was analyzed for creatine kinase ( CK ) , lipid hydroperoxides , malondialdehyde ( MDA ) , and protein carbonyls ( PC ) . Glutathione ratio was determined from whole-blood extracts . RESULTS MS , ROM , MIF , and plasma CK demonstrated significant time effects independent of treatment . MS and plasma CK increased over time , whereas ROM and MIF decreased over time . There was a significant time and time × treatment effect for plasma PC and MDA . PC and MDA increased over time in the P group ( P < 0.01 ) but were not significantly altered in the FVC-treated group at any time . No significant changes were noted in lipid hydroperoxides . The glutathione ratio was elevated immediately postexercise in both groups ( P < 0.01 ) and elevated 6 h postexercise with P compared with the FVC-treated group ( P < 0.05 ) . CONCLUSION This study reports that 4 wk of pretreatment with an FVC can attenuate blood oxidative stress markers induced by EE but had no significant impact on the functional changes related to pain and muscle damage Objective : To investigate whether antioxidant polyphenols from fruit juices or a fruit – vegetable-concentrate increase the plasma antioxidant capacity in HIV-infected and healthy subjects . Design : Twenty-three HIV-seropositive and 18 seronegative adults were r and omized to ingest either 1 l of fruit juice or 30 ml fruit – vegetable-concentrate per day over 16 weeks in addition to their normal Western diet . Methods : Plasma antioxidant capacity was determined as Trolox equivalent antioxidant capacity ( TEAC ) at baseline , after 1 and 16 weeks of intervention , and after a 6 week washout . Results : There was no difference in plasma antioxidant capacity between HIV-infected and healthy subjects at baseline ( P=0.1 ) . After 16 weeks of intervention TEAC increased in HIV-positive subjects with both types of polyphenol supplementation ( juice , 1.38±0.07 to 1.42±0.04 mM , P=0.034 ; concentrate , 1.40±0.09 to 1.46±0.08 mM , P=0.025 ) . TEAC was not altered by either type of supplementation in HIV-seronegative subjects . Conclusion : Plasma antioxidant capacity can be increased by long-term ingestion of polyphenols from fruit juices or fruit – vegetable-concentrate in HIV-seropositive but not in HIV-seronegative subjects . Sponsorship : This study was supported by a grant and Cellagon aurum ® from HG Berner GmbH , Altenholz , and fruit juices from Eckes Granini GmbH & Co. KG , Nieder-Olm . European Journal of Clinical Nutrition ( 2001 ) 55 , Objective : To assess the number of portions of fruit and vegetables consumed daily by a large representative sample of older men , and to determine how blood antioxidant ( vitamins E , A and carotenoids ) concentrations vary with fruit and vegetable consumption . Design : Cross-sectional study of free-living men . Subjects : Men aged 55–69 y ( dietary data , n=1957 ; blood data , n=1874 ) participating in Phase III ( 1989–1993 ) of the Caerphilly and Speedwell Collaborative Heart Disease Studies . Methods : Dietary data were obtained by semi-quantitative food-frequency question naire and blood sample s were analysed for antioxidant vitamins . Men were subdivided into groups on the basis of portions per day of fruit and vegetables . Within these sub-groups , mean and 95 % ranges of intakes and of blood antioxidant levels were obtained . Log transformations were performed where appropriate . Results : Only 4.3 % of the men met the recommended target of five portions , while 33.3 % of the men consumed one or fewer portions of fruit and vegetables per day . Those men who consumed the poorest diets with respect to fruit and vegetable intakes were more likely to be from lower socio-economic classes , drink more alcohol and be current smokers . Fruit and vegetable intake reflected plasma concentrations of antioxidants , which showed a dose – response relationship to frequency of consumption . Conclusions : Older men in the UK consume much less fruit and vegetables than current recommendations . Major difficulties are likely to be encountered in trying to meet a dietary target that is clearly much higher than the fruit and vegetable consumption of large sections of the older population in the UK.Sponsorship : This work was supported by the Medical Research Council . European Journal of Clinical Nutrition ( 2000 ) 54 , Objectives : Using a national representative sample to examine variation in fruit and vegetable consumption among adults in the UK , with particular reference to consumers with high and low reported intakes . Design : National representative dietary survey using 7-d weighed diet records of men and women aged 16–64 y living in private households in the UK in 1986–1987 . Setting : The UK.Subjects : 1087 men and 1110 women . The sample was selected by a multi-stage r and om probability design . The response was 70 % . Subjects with low energy intake were subsequently excluded . Main outcome measures : Food group , nutrient intake , physiological measures socio-economic , demographic and behavioural characterstics . Results : Consumption of fruit and vegetables was estimated . The sample was divided by sex into four quarter groups according to fruit and vegetable consumption . There were significant similarities between quarter groups in fruit and vegetable and other food intake , nutrient intake , physiological measures , and socia-economic , demographic and behavioural variable . The lowest consumers of fruit and vegetables had a mean intake of 738 g/week ( men ) and 630 g/week ( women ) , equivalent to 1.3 and 1.1 portion/d , respectively . Conversely , the mean intake of both men women with the highest consumption was 3137 g/week ( 5.6 portions day ) . There were more than twice as many adults in the age group 16–24 located in Q1 than in Q4 . The Manual social class and those in receipt of benefits were negatively associated with fruit and vegetable consumption . Smokers were significantly associated with low fruit and vegetable intake . Being married was associated with increased fruit and vegetable intake and being single or divorced/separated was associated with low fruit and vegetable intake . Eating home grown produce was associated with hogh intake . Consumers who lived in London or the South-East were associated with higher fruit and vegetable intake . Conclusions : The analysis draws attention to the wide variation in reported fruit and vegetable consumption among British adults . High consumers merit further investigation to eluci date practical strategies for increasing fruit and vegetable consumption . Strategies to increase consumption should be targeted at groups most likely to include low consumers of fruits and vegetables . Sponsorship : London School of Hygience and Tropical Medicine Objective : We investigated whether ingestion of polyphenols from fruit juices or a fruit-vegetable-concentrate affects lymphocyte proliferation and apoptosis in human immunodeficiency virus (HIV)-seropositive ( HIV+ ) and HIV-seronegative ( HIV− ) subjects . Design : R and omized , prospect i ve pilot intervention study . Setting : University of Bonn , Department of General Internal Medicine . Subjects : A total of 23 HIV+ subjects from the HIV outpatient clinic , 18 HIV− controls . Interventions : Subjects ingested either 1 l of fruit juice or 30 ml of fruit-vegetable-concentrate daily for 16 weeks in addition to their regular diet . Lymphocyte proliferation and apoptosis were investigated in peripheral blood mononuclear cells at baseline , during 16-weeks of intervention , and after a 6-week washout . Proliferation was assessed by 3H – thymidine incorporation and apoptosis by nuclear content as measured by flow cytometry . Results : Supplementation of fruit juices increased phytohemagglutinin-induced lymphocyte proliferation ( mitotic index ) in HIV+ patients from 18±16 to 40±34 ( P=0.004 ) and in healthy controls from 27±16 to 51±21 ( P=0.016 ) . Apoptosis was not affected in HIV+ patients , but rose in healthy controls from 9±10 to 34±11 ( apoptotic index ; P=0.001 ) . Intervention with concentrate did not significantly alter proliferation and apoptosis in HIV+ and HIV− subjects . Conclusions : Even though apoptosis did not change in HIV+ subjects , ingestion of polyphenol-rich fruit juices might be favorable to HIV+ patients due to enhanced proliferation , which could restore disturbances in T-cell homeostasis . In healthy controls , increased lymphocyte proliferation during juice consumption was counterbalanced by increased apoptosis . Sponsorship : HG Berner GmbH , Altenholz ; Eckes Granini GmbH & Co. KG , Nieder-Olm ; Graduiertenförderung Nordrhein-Westfalen PURPOSE To assess the effects of different exercise intensities and antioxidant supplementation on plasma protein modification . METHODS Trained men ( n = 41 ) from a homogenous population were r and omly assigned to perform cycle ergometer exercise either at 70 % or 80 % of individual .VO2max . Each intensity group was r and omly assigned to receive either juice powder concentrate ( JPC 70 % , n = 11 ; JPC 80 % , n = 10 ) or placebo ( Plac 70 % , n = 10 ; Plac 80 % , n = 10 ) capsules for 28 wk . Four controlled exercise bouts and blood collection s were conducted at baseline and study weeks 4 , 16 , and 28 . Blood sample s were drawn before ( BE ) , immediately after ( IE ) , and 30 min ( 30 M ) and 30 h ( 30H ) postexercise . These sample s were analyzed to estimate concentrations of carbonyl groups on plasma proteins ( CP ) and the redox state of human serum albumin ( HSA ) . RESULTS In the Plac group , CP concentrations increased at 80 % of .VO2max IE and 30 M , returning to preexercise concentrations by 30H ( P < 0.05 ) . At both 16 and 28 wk , the Plac groups had significantly higher BE and 30H CP concentrations than the JPC groups ( P < 0.05 ) . The reduced fraction of HSA , human mercaptalbumin ( HMA ) , decreased at all four exercise tests at both exercise intensities IE and 30 M , returning to preexercise values by 30H ( P < 0.05 ) . Supplementation had no influence on HSA . CONCLUSIONS These results indicate that CP concentrations increase with 80 % .VO2max intensity . The JPC group had lower baseline CP levels after 16 and 28 wk and no exercise-induced CP increase . HSA is reversibly shifted to a more oxidized state by recent intense exercise Healthy overweight subjects ( 24 males , 68 females ; mean age=48.8 years ; body mass index=27.1±4.9 ) participated in a r and omized , double-blind , placebo-controlled crossover study with two periods of 28-day supplementation using a nutritional product composed primarily of dehydrated juice concentrates from mixed fruits and vegetables ( JuicePlus + ® ) . Compared with placebo , supplementation for 28 days increased concentrations of serum β-carotene by 264 % ( P < 0.001 ) and α-tocopherol by 14 % ( P < 0.01 ) . After crossover of the active group to placebo , β-carotene and α-tocopherol declined via first-order kinetics , with serum half-lives ( t1/2 ) for β-carotene and α-tocopherol determined to be 22.8±3.1 and 4.6±2.3 days , respectively . Depletion rates for β-carotene correlated with adiposity ( quartile 1 , body mass index=21.96 , t1/2=17.6 days vs. quartile 4 , body mass index=37.87 , t1/2=26.3 days ; P < 0.05 ) . In conclusion , the supplementation period result ed in significantly elevated levels of β-carotene and α-tocopherol , indicating bioavailability . These increased levels persisted 2–4 weeks after supplementation was discontinued , and the rates of depletion were correlated with the levels of general adiposity The purpose of this study was to determine the influence of gender and antioxidant supplementation on exercise-induced oxidative stress . Twenty-five men and 23 women ran for 30 min at 80 % VO2 max , once before and once after 2 weeks of supplementation , and again after a 1-week wash-out period . Subjects were r and omly assigned to either placebo ( P ) , antioxidant ( A : 400 IU vitamin E+1 g vitamin C ) , or a fruit and vegetable powder ( FV ) treatment . Blood was obtained at rest and immediately after exercise . Before supplementation , women had higher resting reduced glutathione , total glutathione , and plasma vitamin E compared with men . With both A and FV supplementations , plasma vitamin E gender differences disappeared . Protein carbonyls , oxidized glutathione , and malondialdehyde all increased similarly for both genders in response to exercise . Both A and FV attenuated the reduced glutathione decrease and the oxidized glutathione and protein carbonyls increase compared with P , with no gender differences . 8-hydroxydeoxyguanosine was lower with treatment A compared with FV and P only for men . Plasma vitamin C increased 39 % ( A ) and 21 % ( FV ) compared with P. These data indicate that women have higher resting antioxidant levels than men . Markers of oxidative stress increased similarly in both genders in response to exercise of similar intensity and duration . Two weeks of antioxidant supplementation can attenuate exercise-induced oxidative stress equally in both genders Objective : Epidemiological studies have shown that low plasma levels of antioxidant micronutrients , which are commonly found in fruit and vegetables , are associated with increased risk for diseases such as heart disease , cancer , metabolic disorders and the like . The aim of this study was to monitor the dietary habits of a group of healthy , middle-aged , men and women and to assess the effect of supplementation with a natural phytonutrient preparation from fruits and vegetables , on plasma levels of various antioxidant micronutrients and oxidative stress assessed by measuring 8-oxodGuo ( 8-oxo-7,8-dihydro-2′-deoxyguanosine ) in urine . Methods : The study followed a double-blind r and omized cross-over design involving 59 healthy men and women ( 40–60 years of age ) . The supplement or a placebo was given to two groups for a total period of 14 weeks ( crossover week 7 ) . Blood levels of β-carotene , vitamin C , vitamin E , selenium and folate were measured at 0 , 7 and 14 weeks . Fruit and vegetable consumption was monitored by means of a retrospective food frequency question naire at week 0 , 7 and 14 . Urinary 8-oxodGuo was also determined at these time points . Results : Significant increases in blood nutrient levels after active supplementation were observed for β-carotene , vitamin C , vitamin E , selenium and folate . Ranges measured , after supplementation , often fell into those associated with a reduced risk for disease . Our data suggests that , although generally health conscious , participants still fell short of the recommended five portions of fruit and vegetables per day . No significant group changes were noted for 8-oxodGuo concentration in urine . Conclusion : Supplementation with mixed fruit and vegetable juice concentrates effectively increased plasma levels of important antioxidant nutrients and folate |
2,135 | 28,963,884 | Interventions that included yoga asanas were associated with reduced evening cortisol , waking cortisol , ambulatory systolic blood pressure , resting heart rate , high frequency heart rate variability , fasting blood glucose , cholesterol and low density lipoprotein , compared to active control .
Practice s that include yoga asanas appear to be associated with improved regulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal system in various population | BACKGROUND AND OBJECTIVES Practice s that include yoga asanas and mindfulness-based stress reduction for the management of stress are increasingly popular ; however , the neurobiological effects of these practice s on stress reactivity are not well understood .
Many studies investigating the effects of such practice s fail to include an active control group .
Given the frequency with which people are selecting such interventions as a form of self-management , it is important to determine their effectiveness .
Thus , this review investigates the effects of practice s that include yoga asanas , with and without mindfulness-based stress reduction , compared to an active control , on physiological markers of stress . | Objective . To examine the effects of yoga versus an educational film program on sleep , mood , perceived stress , and sympathetic activation in older women with RLS . Methods . Participants were drawn from a larger trial regarding the effects of yoga on cardiovascular disease risk profiles in overweight , sedentary postmenopausal women . Seventy-five women were r and omized to receive either an 8-week yoga ( n = 38 ) or educational film ( n = 37 ) program . All 75 participants completed an RLS screening question naire . The 20 women who met all four diagnostic criteria for RLS ( n = 10 yoga , 10 film group ) comprised the population for this nested study . Main outcomes assessed pre- and post-treatment included : sleep ( Pittsburgh Sleep Quality Index ) , stress ( Perceived Stress Scale ) , mood ( Profile of Mood States , State-Trait Anxiety Inventory ) , blood pressure , and heart rate . Results . The yoga group demonstrated significantly greater improvements than controls in multiple domains of sleep quality and mood , and significantly greater reductions in insomnia prevalence , anxiety , perceived stress , and blood pressure ( all P's≤0.05 ) . Adjusted intergroup effect sizes for psychosocial variables were large , ranging from 1.9 for state anxiety to 2.6 for sleep quality . Conclusions . These preliminary findings suggest yoga may offer an effective intervention for improving sleep , mood , perceived stress , and blood pressure in older women with RLS Objectives : Fibromyalgia ( FM ) is a syndrome characterized by severe pain , fatigue and sleep disturbance . There is evidence of central hyper-responsiveness to sensory stimulation and impaired cardiovascular autonomic control . Laboratory investigations suggest that mindfulness-based stress reduction ( MBSR ) may improve autonomic functioning in FM . However , these findings may not reflect what occurs during naturalistic conditions , and MBSR studies during real-life functioning are lacking . We conducted a r and omized controlled , 3-armed study with 168 female FM patients . This report describes cardiac , respiratory , and physical activity findings . Methods : Eight-week MBSR was compared with wait-list and active control intervention . Ambulatory accelerometry and cardiorespiratory function were monitored over 24-h periods at 3 time points : preintervention , postintervention , and at the 8-week follow-up . Also , baseline levels were compared with an age-matched group of 33 healthy women . Findings : Activity heart rate , respiratory sinus arrhythmia , and ventilation were measured . Comparison with controls confirmed differences in cardiac autonomic tone and activity pattern among patients . Most measures also showed effects of time of day and point of measurement . Regarding the intervention study , there were no effects of treatment . In addition , there were no relations between patient-reported clinical improvement and objective physiological or accelerometry parameters . Intervention-related benefits in wellbeing were not associated with changes in daytime cardiorespiratory measures or pattern of physical activity . Conclusions : MBSR did not produce cardiac autonomic benefits or changes in daily activity in FM . Furthermore , the lack of an association between patient-experienced clinical improvement and objective physiological measures suggests that subjective changes in the wellbeing of FM patients over time are not related to alterations in the cardiorespiratory autonomic function or activity levels OBJECTIVE This study aim ed to develop and test a novel mindfulness-based intervention ( MBI ) design ed to control weight after bariatric surgery . DESIGN R and omized , controlled pilot trial . SETTING Beth Israel Deaconess Medical Center , Boston , MA , USA . INTERVENTIONS Bariatric patients 1 - 5 years post-surgery ( n=18 ) were r and omized to receive a 10-week MBI or a st and ard intervention . MAIN OUTCOME MEASURES Primary outcomes were feasibility and acceptability of the MBI . Secondary outcomes included changes in weight , eating behaviors , psychosocial outcomes , and metabolic and inflammatory biomarkers . Qualitative exit interviews were conducted post-intervention . Major themes were coded and extracted . RESULTS Attendance was excellent ( 6 of 9 patients attended ≥7 of 10 classes ) . Patients reported high satisfaction and overall benefit of the MBI . The intervention was effective in reducing emotional eating at 6 months ( -4.9±13.7 in mindfulness vs. 6.2±28.4 in st and ard , p for between-group difference=0.03 ) but not weight . We also observed a significant increase in HbA1C ( 0.34±0.38 vs. -0.06±0.31 , p=0.03 ) . Objective measures suggested trends of an increase in perceived stress and symptoms of depression , although patients reported reduced stress reactivity , improved eating behaviors , and a desire for continued mindfulness-based support in qualitative interviews . CONCLUSIONS This novel mindfulness-based approach is highly acceptable to bariatric patients post-surgery and may be effective for reducing emotional eating , although it did not improve weight or glycemic control in the short term . Longer-term studies of mindfulness-based approaches may be warranted in this population . CLINICAL TRIAL REGISTRATION Clinical Trials.gov identifier NCT02603601 We have developed a low dose Mindfulness-Based Intervention ( MBI-ld ) that reduces the time committed to meetings and formal mindfulness practice , while conducting the sessions during the workday . This reduced the barriers commonly mentioned for non-participation in mindfulness programs . In a controlled r and omized trial we studied university faculty and staff ( n=186 ) who were found to have an elevated CRP level,>3.0 mg/ml , and who either had , or were at risk for cardiovascular disease . This study was design ed to evaluate if MBI-ld could produce a greater decrease in CRP , IL-6 and cortisol than an active control group receiving a lifestyle education program when measured at the end of the 2 month interventions . We found that MBI-ld significantly enhanced mindfulness by 2-months and it was maintained for up to a year when compared to the education control . No significant changes were noted between interventions in cortisol , IL-6 levels or self-reported measures of perceived stress , depression and sleep quality at 2-months . Although not statistically significant ( p=.08 ) , the CRP level at 2-months was one mg/ml lower in the MBI-ld group than in the education control group , a change which may have clinical significance ( Ridker et al. , 2000 ; Wassel et al. , 2010 ) . A larger MBI-ld effect on CRP ( as compared to control ) occurred among participants who had a baseline BMI < 30 ( -2.67 mg/ml ) than for those with BMI > 30 ( -0.18 mg/ml ) . We conclude that MBI-ld should be more fully investigated as a low-cost self-directed complementary strategy for decreasing inflammation , and it seems most promising for non-obese subjects BACKGROUND Despite recent advances in pharmacologic and device therapy , morbidity and mortality from heart failure ( HF ) remain high . Yoga combines physical and breathing exercises that may benefit patients with HF . We hypothesized that an 8-week regimen of yoga in addition to st and ard medical therapy would improve exercise capacity , inflammatory markers , and quality of life ( QoL ) in patients with HF . METHODS AND RESULTS New York Heart Association Class I-III HF patients were r and omized to yoga treatment ( YT ) or st and ard medical therapy ( MT ) . Measurements included a grade d exercise test ( GXT ) to V O(2Peak ) and the following serum biomarkers : interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) , and extracellular superoxide dismutase ( EC-SOD ) . The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was administered to assess changes in QoL. A total of 19 patients were enrolled after the initial screening . Of the 19 patients , 9 were r and omized to YT and 10 to MT . Patients had a mean EF of 25 % . GXT time and V O(2Peak ) were significantly improved in the YT versus MT groups ( + 18 % in the YT and -7.5 % in MT ; P = .03 vs. control and + 17 in YT and -7.1 in MT ; P = .02 , respectively ) . There were statistically significant reductions in serum levels of IL-6 and hsCRP and an increase in EC-SOD in the YT group ( all P < .005 vs. MT ) . MLHFQ scores improved by 25.7 % in the YT group and by 2.9 % in the MT group . CONCLUSIONS Yoga improved exercise tolerance and positively affected levels of inflammatory markers in patients with HF , and there was also a trend toward improvements in This study reports the physiologic effects of up to 14 months of aerobic exercise in 101 older ( greater than 60 years ) men and women . After an extensive baseline physiologic assessment ( Time 1 ) , in which aerobic capacity and blood lipids were measured , subjects were r and omized to an aerobic exercise condition ( cycle ergometry , 3 times per week for 1 hour ) , nonaerobic yoga ( 2 times per week for 1 hour ) , or a waiting list nonexercise control group for 4 months , and then underwent a second ( Time 2 ) assessment . At the completion of the second assessment , all remaining subjects completed 4 months of aerobic exercise and were reevaluated ( Time 3 ) . Subjects were given the option of participating in 6 additional months of supervised aerobic exercise , and all available subjects completed a fourth assessment ( Time 4 ) 14 months after their initial baseline evaluation . Results indicated that subjects generally exhibited a 10 to 15 % improvement in peak oxygen consumption after 4 months of aerobic exercise training , and a 1 to 6 % improvement in aerobic power with additional aerobic exercise training . On the other h and , subjects , especially men , continued to have improvements in submaximal exercise performance ( i.e. , anaerobic threshold ) . In addition , aerobic exercise was associated with an improved lipid profile ; subjects participating in aerobic exercise for up to 14 months exhibited increased levels of high-density lipoprotein cholesterol . Maintenance of regular aerobic exercise for an extended time interval is associated with greater cardiovascular benefits among older adults than has been reported previously PURPOSE To compare the efficacy of the following two empirically supported group interventions to help distressed survivors of breast cancer cope : mindfulness-based cancer recovery ( MBCR ) and supportive-expressive group therapy ( SET ) . PATIENTS AND METHODS This multisite , r and omized controlled trial assigned 271 distressed survivors of stage I to III breast cancer to MBCR , SET , or a 1-day stress management control condition . MBCR focused on training in mindfulness meditation and gentle yoga , whereas SET focused on emotional expression and group support . Both intervention groups included 18 hours of professional contact . Measures were collected at baseline and after intervention by assessors blind to study condition . Primary outcome measures were mood and diurnal salivary cortisol slopes . Secondary outcomes were stress symptoms , quality of life , and social support . RESULTS Using linear mixed-effects models , in intent-to-treat analyses , cortisol slopes were maintained over time in both SET ( P = .002 ) and MBCR ( P = .011 ) groups relative to the control group , whose cortisol slopes became flatter . Women in MBCR improved more over time on stress symptoms compared with women in both the SET ( P = .009 ) and control ( P = .024 ) groups . Per- protocol analyses showed greater improvements in the MBCR group in quality of life compared with the control group ( P = .005 ) and in social support compared with the SET group ( P = .012 ) . CONCLUSION In the largest trial to date , MBCR was superior for improving stress levels , quality of life and social support [ CORRECTED ] for distressed survivors of breast cancer . Both SET and MBCR also result ed in more normative diurnal cortisol profiles than the control condition . The clinical implication s of this finding require further investigation Complementary medicine advocates the use of a multifactorial approach to address the varied aspects of hypertension . The aim of this study was to compare the blood pressure ( BP ) effect and medication use of a novel Comprehensive Approach to Lowering Measured Blood Pressure ( CALM-BP ) , based on complementary medicine principles , with the st and ard recommended Dietary Approach to Stop Hypertension ( DASH ) . A total of 113 patients treated with antihypertensive drugs were r and omly assigned to either CALM-BP treatment ( consisting of rice diet , walks , yoga , relaxation and stress management ) or to a DASH+exercise control group ( consisting of DASH and walks ) . Ambulatory 24-h and home BP were monitored over a 16-week programme , followed by 6 months of maintenance period . Medications were reduced if systolic BP dropped below 110 mm Hg accompanied by symptoms . In addition to BP reduction , medications were reduced because of symptomatic hypotension in 70.7 % of the CALM-BP group compared with 32.7 % in the DASH group , P<0.0001 . After 6 months , medication status was not altered in the majority of individuals . Significant reductions in body mass index , cholesterol and improved quality -of-life scores were observed only in the CALM-BP group . Lifestyle and diet modifications based on complementary medicine principles are highly effective with respect to BP control , medication use and cardiovascular risk factors In this study , a stress management program based on cognitive behavioural therapy principles was compared with a Kundaliniyoga program . A study sample of 26 women and 7 men from a large Swedish company were divided r and omly into 2 groups for each of the different forms of intervention ; a total of 4 groups . The groups were instructed by trained group leaders and 10 sessions were held with each of groups , over a period of 4 months . Psychological ( self‐rated stress and stress behaviour , anger , exhaustion , quality of life ) and physiological ( blood pressure , heart rate , urinary catecholamines , salivary cortisol ) measurements obtained before and after treatment showed significant improvements on most of the variables in both groups as well as medium‐to‐high effect sizes . However , no significant difference was found between the 2 programs . The results indicate that both cognitive behaviour therapy and yoga are promising stress management techniques The authors conducted a study to assess the effects of yoga on blood pressure ( BP ) . Patients were r and omized to yoga ( Blood Pressure Education Program [ BPEP ] ) , or a combined program ( COMBO ) . Ambulatory BP was measured at baseline and at 12 and 24 weeks . Data are presented for all enrolled patients ( n=137 ) and for completers only ( n=90 ) . Systolic BP ( SBP ) and diastolic BP ( DBP ) were significantly decreased within all groups at 12 and 24 weeks ( P<.001 ) for enrolled patients and completers . SBP was significantly reduced in the yoga and COMBO groups as compared with the BPEP group at 12 weeks in all enrolled and completers . SBP differences were no longer significant at 24 weeks between groups in all enrolled patients ; however , there was a greater reduction in SBP at 24 weeks in completers favoring BPEP over yoga . No differences in DBP between groups or in BP between the yoga and COMBO groups were present . The authors did not observe an additive benefit from combining yoga with BPEP measures . Reasons for this are unclear at this time . BP lowering with yoga , however , was similar to that achieved with lifestyle measures OBJECTIVE Evidence is accumulating , predominantly among clinical trials in adults , that yoga improves blood pressure ( BP ) control , with downregulation of the hypothalamic-pituitary-adrenal ( HPA ) axis and the sympathetic nervous system ( SNS ) projected as underlying mechanisms . This pilot study assessed whether Hatha yoga has the potential to reduce BP among youth and whether dampening of the SNS and /or HPA activity is a likely pathway of change . DESIGN Thirty-one seventh grade rs were r and omly assigned to a Hatha yoga program ( HYP ) or attention control ( AC ) music or art class . Baseline and 3-month evaluations included resting BP ; overnight urine sample s ; and saliva collected at bedtime , upon awakening , and at 30 and 60 minutes after awakening for α-amylase and cortisol assays . RESULTS Twenty-eight ( 14 in the HYP group and 14 in the AC group ) students were assessed both before and after the intervention . BP changes from pre- to post-intervention were -3.0/-2.0 mmHg for the HYP group and -0.07/-0.79 mmHg for the AC group ( p=0.30 and 0.57 , respectively ) . Changes in systolic BP (SBP)/diastolic BP ( DBP ) for the prehypertensive ( 75th-94th percentiles for SBP ) subgroup analyses were -10.75/-8.25 mmHg for the HYP group ( n=4 ) versus 1.8/1.0 mmHg for the AC group ( n=5 ) ( p for SBP=0.02 ; p for DBP=0.09 ) . Although no statistically significant group differences were observed with changes in SNS or HPA awakening curves ( area under curve for α-amylase and cortisol , respectively ) , a small to moderate effect size was seen favoring a reduction of α-amylase activation for the HYP group ( Cohen d=0.34 ; prehypertensive d=0.20 ) . CONCLUSIONS A school-based Hatha yoga program demonstrated potential to decrease resting BP , particularly among prehypertensive youth . Reduced SNS drive may be an underlying neurohormonal pathway beneficially affected by the program . A large-scale efficacy/effectiveness r and omized clinical trial is warranted Objectives . This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer out patients undergoing adjuvant radiotherapy at a cancer center . Methods . Eighty-eight stage II and III breast cancer out patients are r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to radiotherapy treatment . Assessment s include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety , depression , and stress collected before and after 6 weeks of radiotherapy . Results . Analysis of covariance reveals significant decreases in anxiety ( P < .001 ) , depression ( P = .002 ) , perceived stress ( P < .001 ) , 6 a.m. salivary cortisol ( P = .009 ) , and pooled mean cortisol ( P = .03 ) in the yoga group compared with controls . There is a significant positive correlation between morning salivary cortisol level and anxiety and depression . Conclusion . Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy BACKGROUND The number of African American ( AA ) patients living with heart failure ( HF ) has been increasing , especially among the economically disadvantaged . Yoga therapy has been found to improve physical and psychological parameters among healthy individuals , but its effect in patients with HF remains unknown . The purpose of this study was to examine the effects of yoga therapy on cardiovascular endurance ( VO2peak ) , flexibility , quality of life ( QoL ) , and inflammatory markers on medically stable HF patients . METHODS Forty patients ( 38 AA , 1 Asian , and 1 Caucasian ) with systolic or diastolic HF were r and omized to the yoga group ( YG , n = 21 ) or the control group ( CG , n = 19 ) . All patients were asked to follow a home walk program . Premeasurement and postmeasurement included a treadmill stress test to peak exertion , flexibility , interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) , and extracellular superoxide dismutase ( EC-SOD ) . QoL was assessed by the Minnesota Living with Heart Failure Question naire ( MLwHFQ ) . RESULTS The statistical analyses ( assessed by ANOVA and t-tests ) were significant for favorable changes in the YG , compared with those in the CG , for flexibility ( P = 0.012 ) , treadmill time ( P = 0.002 ) , VO2peak ( P = 0.003 ) , and the biomarkers ( IL-6 , P = 0.004 ; CRP , P = 0.016 ; and EC-SOD , P = 0.012 ) . Within the YG , pretest to posttest scores for the total ( P = 0.02 ) and physical subscales ( P < 0.001 ) of the MLwHFQ were improved . CONCLUSIONS Yoga therapy offered additional benefits to the st and ard medical care of predominantly AA HF patients by improving cardiovascular endurance , QoL , inflammatory markers , and flexibility Serum lipids have been associated with depression in the adult population ; however , this association during pregnancy remains unclear . The aim of this study was to evaluate the association between serum lipids and depressive symptom scores during pregnancy . A prospect i ve cohort of 238 pregnant women was followed at the 5th-13th , 20th-26th and 30th-36th weeks of gestation . Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale ( EPDS ) . Serum concentrations ( mg/dL ) of triglycerides , total cholesterol , and low- and high-density lipoproteins ( LDL-c ; HDL-c ) were the main exposures . Marital status ( married/single ) , physical activity ( active or very active/low or very low active ) , unplanned pregnancy ( no/yes ) , pre-pregnancy BMI ( < 25/≥ 25 kg/m(2 ) ) , generalized anxiety disorder ( no/yes ) and current suicidal ideation ( no/yes ) were considered as potential confounders . Analyses were performed using linear mixed-effects models . The results showed that the EPDS mean score ( 95%CI ) decreased with time during pregnancy trimesters [ 1st : 8.89 ( 95%CI = 8.28 - 9.51 ) , 2nd : 7.32 ( 95%CI = 6.67 - 7.97 ) and 3rd : 7.08 ( 95%CI = 6.41 - 7.74 ) ] . Suicidal ideation frequency at baseline was 18 % . HDL-c concentrations were inversely associated with changes in EPDS score ( β = -0.080 , 95%CI = -0.157 to -0.002 ) , while low or very low active women ( β = 1.288 , 95%CI = 0.630 - 1.946 ) , with single marital status ( β = 1.348 , 95%CI = 0.163 - 2.534 ) , unplanned pregnancy ( β = 1.922 , 95%CI = 0.714 - 3.131 ) , generalized anxiety disorder ( β = 2.139 , 95%CI = 0.410 - 3.868 ) and current suicidal ideation ( β = 1.927 , 95%CI = 0.596 - 3.258 ) tended to have higher EPDS scores . No relationship was observed between other lipids and EPDS scores . HDL-c concentration was inversely associated with changes in depressive symptom scores during pregnancy after adjusting for socio-economic , demographic , behavioral , nutritional , biochemical and mental health disorders PURPOSE To evaluate yoga 's impact on inflammation , mood , and fatigue . PATIENTS AND METHODS A r and omized controlled 3-month trial was conducted with two post-treatment assessment s of 200 breast cancer survivors assigned to either 12 weeks of 90-minute twice per week hatha yoga classes or a wait-list control . The main outcome measures were lipopolysaccharide-stimulated production of proinflammatory cytokines interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-α ) , and interleukin-1β ( IL-1β ) , and scores on the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) , the vitality scale from the Medical Outcomes Study 36-item Short Form ( SF-36 ) , and the Center for Epidemiological Studies -Depression ( CES-D ) scale . RESULTS Immediately post-treatment , fatigue was not lower ( P > .05 ) but vitality was higher ( P = .01 ) in the yoga group compared with the control group . At 3 months post-treatment , fatigue was lower in the yoga group ( P = .002 ) , vitality was higher ( P = .01 ) , and IL-6 ( P = .027 ) , TNF-α ( P = .027 ) , and IL-1β ( P = .037 ) were lower for yoga participants compared with the control group . Groups did not differ on depression at either time ( P > .2 ) . Planned secondary analyses showed that the frequency of yoga practice had stronger associations with fatigue at both post-treatment visits ( P = .019 ; P < .001 ) , as well as vitality ( P = .016 ; P = .0045 ) , but not depression ( P > .05 ) than simple group assignment ; more frequent practice produced larger changes . At 3 months post-treatment , increasing yoga practice also led to a decrease in IL-6 ( P = .01 ) and IL-1β ( P = .03 ) production but not in TNF-α production ( P > .05 ) . CONCLUSION Chronic inflammation may fuel declines in physical function leading to frailty and disability . If yoga dampens or limits both fatigue and inflammation , then regular practice could have substantial health benefits Context : Resting heart rate variability ( HRV ) is a measure of the modulation of autonomic nervous system ( ANS ) at rest . Increased HRV achieved by the exercise is good for the cardiovascular health . However , prospect i ve studies with comparison of the effects of yogic exercises and those of other endurance exercises like walking , running , and swimming on resting HRV are conspicuous by their absence . Aims : Study was design ed to assess and compare the effects of yogic training and swimming on resting HRV in normal healthy young volunteers . Setting s and Design : Study was conducted in Department of Physiology in a medical college . Study design was prospect i ve r and omized comparative trial . Subjects and Methods : One hundred sedentary volunteers were r and omly ascribed to either yoga or swimming group . Baseline recordings of digital electrocardiogram were done for all the subjects in cohorts of 10 . After yoga training and swimming for 12 weeks , evaluation for resting HRV was done again . Statistical Analysis Used : Percentage change for each parameter with yoga and swimming was compared using unpaired t-test for data with normal distribution and using Mann-Whitney U test for data without normal distribution . Results : Most of the HRV parameters improved statistically significantly by both modalities of exercise . However , some of the HRV parameters showed statistically better improvement with yoga as compared to swimming . Conclusion : Practicing yoga seems to be the mode of exercise with better improvement in autonomic functions as suggested by resting HRV BACKGROUND Yoga is a popular mind-body therapy that has demonstrated beneficial effects on psychological , behavioral , and functional outcomes . However , few studies have investigated effects on inflammatory processes . This study tested the hypothesis that an Iyengar yoga intervention specifically design ed for fatigued breast cancer survivors would lead to decreases in inflammation-related gene expression and circulating markers of proinflammatory cytokine activity . METHODS Breast cancer survivors with persistent cancer-related fatigue were r and omized to a 12-week Iyengar yoga intervention ( n=16 ) or a 12-week health education control condition ( n=15 ) . Blood sample s were collected at baseline , post-intervention , and at a 3-month follow-up for genome-wide transcriptional profiling and bioinformatic analyses . Plasma inflammatory markers and salivary cortisol were also assessed . RESULTS In promoter-based bioinformatics analyses , the yoga group showed reduced activity of the pro-inflammatory transcription factor nuclear factor kappa B ( NF-κB ) , increased activity of the anti-inflammatory glucocorticoid receptor , and reduced activity of cAMP response element-binding protein ( CREB ) family transcription factors relative to controls ( all ps<.05 ) . There was also a significant intervention effect on the soluble tumor necrosis factor receptor type II ( sTNF-RII ) , a marker of TNF activity ; plasma levels of sTNF-RII remained stable in the yoga group , whereas levels of this marker increased in the health education group ( p=.028 ) . A similar , non-significant trend was observed for the interleukin 1 receptor antagonist ( p=.16 ) . No significant changes in C reactive protein ( CRP ) , interleukin 6 ( IL-6 ) , or diurnal cortisol measures were observed . CONCLUSIONS A 12-week restorative Iyengar yoga intervention reduced inflammation-related gene expression in breast cancer survivors with persistent fatigue . These findings suggest that a targeted yoga program may have beneficial effects on inflammatory activity in this patient population , with potential relevance for behavioral and physical health OBJECTIVES Stress is a well-known predictor of smoking relapse , and cortisol is a primary biomarker of stress . The current pilot study examined changes in levels of cortisol in hair within the context of two time-intensity matched behavioral smoking cessation treatments : mindfulness training for smokers and a cognitive-behavioral comparison group . PARTICIPANTS Eighteen participants were recruited from a larger r and omized controlled trial of smoking cessation . OUTCOME MEASURES Hair sample s ( 3 cm ) were obtained 1 month after quit attempt , allowing for a retrospective analysis of hair cortisol at preintervention and post-quit attempt time periods . Self-reported negative affect was also assessed before and after treatment . INTERVENTION Both groups received a 7-week intensive intervention using mindfulness or cognitive-behavioral strategies . RESULTS Cortisol significantly decreased from baseline to 1 month after quit attempt in the entire sample ( d=-0.35 ; p=.005 ) . In subsequent repeated- measures analysis of variance models , time by group and time by quit status interaction effects were not significant . However , post hoc paired t tests yielded significant pre-post effects among those r and omly assigned to the mindfulness condition ( d=-0.48 ; p=.018 ) and in those abstinent at post-test ( d=-0.41 ; p=.004 ) . Decreased hair cortisol correlated with reduced negative affect ( r=.60 ; p=.011 ) . CONCLUSIONS These preliminary findings suggest that smoking cessation intervention is associated with decreased hair cortisol levels and that reduced hair cortisol may be specifically associated with mindfulness training and smoking abstinence . RESULTS support the use of hair cortisol as a novel objective biomarker in future research Various modes of physical activity , combined with dieting , have been widely recommended to prevent or delay type 2 diabetes . Among these , yoga holds promise for reducing risk factors for type 2 diabetes by promoting weight loss , improving glucose levels and reducing blood pressure and lipid levels . This pilot study aim ed to assess the feasibility of implementing a 12-week yoga program among adults at high risk for type 2 diabetes . Twenty-three adults ( 19 Whites and 4 non-Whites ) were r and omly assigned to the yoga intervention group or the educational group . The yoga group participated in a 3-month yoga intervention with sessions twice per week and the educational group received general health educational material s every 2 weeks . All participants completed question naires and had blood tests at baseline and at the end of 3 months . Effect sizes were reported to summarize the efficacy of the intervention . All participants assigned to the yoga intervention completed the yoga program without complication and expressed high satisfaction with the program ( 99.2 % ) . Their yoga session attendance ranged from 58.3 to 100 % . Compared with the education group , the yoga group experienced improvements in weight , blood pressure , insulin , triglycerides and exercise self-efficacy indicated by small to large effect sizes . This preliminary study indicates that a yoga program would be a possible risk reduction option for adults at high risk for type 2 diabetes . In addition , yoga holds promise as an approach to reducing cardiometabolic risk factors and increasing exercise self-efficacy for this group The prevalence of prehypertension and Stage 1 hypertension continues to increase despite being amenable to non-pharmacologic interventions . Iyengar yoga ( IY ) has been purported to reduce blood pressure ( BP ) though evidence from r and omized trials is lacking . We conducted a r and omized controlled trial to assess the effects of 12 weeks of IY versus enhanced usual care ( EUC ) ( based on individual dietary adjustment ) on 24-h ambulatory BP in yoga-naïve adults with untreated prehypertension or Stage 1 hypertension . In total , 26 and 31 subjects in the IY and EUC arms , respectively , completed the study . There were no differences in BP between the groups at 6 and 12 weeks . In the EUC group , 24-h systolic BP ( SBP ) , diastolic BP ( DBP ) and mean arterial pressure ( MAP ) significantly decreased by 5 , 3 and 3 mmHg , respectively , from baseline at 6 weeks ( P < .05 ) , but were no longer significant at 12 weeks . In the IY group , 24 h SBP was reduced by 6 mmHg at 12 weeks compared to baseline ( P = .05 ) . 24 h DBP ( P < .01 ) and MAP ( P < .05 ) decreased significantly each by 5 mmHg . No differences were observed in catecholamine or cortisol metabolism to explain the decrease in BP in the IY group at 12 weeks . Twelve weeks of IY produces clinical ly meaningful improvements in 24 h SBP and DBP . Larger studies are needed to establish the long term efficacy , acceptability , utility and potential mechanisms of IY to control BP Objective Mindfulness-based stress reduction ( MBSR ) is an increasingly popular practice demonstrated to alleviate stress and treat certain health conditions . MBSR may reduce elevated blood pressure ( BP ) . Treatment guidelines recommend life-style modifications for BP in the prehypertensive range ( systolic BP [ SBP ] 120–139 mm Hg or diastolic BP [ DBP ] 80–89 mm Hg ) , followed by antihypertensives if BP reaches hypertensive levels . MBSR has not been thoroughly evaluated as a treatment of prehypertension . A r and omized clinical trial of MBSR for high BP was conducted to determine whether BP reductions associated with MBSR exceed those observed for an active control condition consisting of progressive muscle relaxation ( PMR ) training . Methods Fifty-six men ( 43 % ) and women ( 57 % ) averaging ( st and ard deviation ) 50.3 ( 6.5 ) years of age ( 91 % white ) with unmedicated BP in the prehypertensive range were r and omized to 8 weeks of MBSR or PMR delivered in a group format . Treatment sessions were administered by one treatment provider and lasted approximately 2.5 hours each week . Clinic BP was the primary outcome measure . Ambulatory BP was a secondary outcome measure . Results Analyses were based on intent to treat . Patients r and omized to MBSR exhibited a 4.8-mm Hg reduction in clinic SBP , which was larger than the 0.7-mm Hg reduction observed for PMR ( p = .016 ) . Those r and omized to MBSR exhibited a 1.9-mm Hg reduction in DBP compared with a 1.2-mm Hg increase for PMR ( p = .008 ) . MBSR did not result in larger decreases in ambulatory BP than in PMR . Conclusions MBSR result ed in a reduction in clinic SBP and DBP compared with PMR . Trial Registration Clinical Trials.gov identifier : NCT00440596 Background : Strategies to improve influenza vaccine protection among elderly individuals are an important research priority . Mindfulness-based stress reduction ( MBSR ) and exercise have been shown to affect aspects of immune function in some population s. We hypothesized that influenza vaccine responses may be enhanced with meditation or exercise training as compared with controls . Results : No differences in vaccine responses were found comparing control to MBSR or exercise . Individuals achieving seroprotective levels of influenza antibody ≥160 units had higher optimism , less anxiety , and lower perceived stress than the nonresponders . Age correlated with influenza antibody responses , but not with IFNγ or IL-10 production . Conclusion : The MBSR and exercise training evaluated in this study failed to enhance immune responses to influenza vaccine . However , optimism , perceived stress , and anxiety were correlated in the expected directions with antibody responses to influenza vaccine . Methods : Healthy individuals ≥50 y were r and omly assigned to exercise ( n = 47 ) or MBSR ( n = 51 ) training or a waitlist control condition ( n = 51 ) . Each participant received trivalent inactivated influenza vaccine after 6 weeks , and had blood draws prior to and 3 and 12 weeks after immunization . Serum influenza antibody , nasal immunoglobulin A , and peripheral blood mononuclear cell interferon-γ ( IFNγ ) and interleukin-10 ( IL-10 ) concentrations were measured . Measures of optimism , perceived stress , and anxiety were obtained over the course of the study . Seroprotection was defined as an influenza antibody concentration ≥160 units . Vaccine responses were compared using ANOVA , t tests , and Kruskal – Wallis tests . The correlation between vaccine responses and age was examined with the Pearson test Hypertension affects a large proportion of urban African-American older adults . While there have been great strides in drug development , many older adults do not have access to such medicines or do not take them . Mindfulness-based stress reduction ( MBSR ) has been shown to decrease blood pressure in some population s. This has not been tested in low-income , urban African-American older adults . Therefore , the primary purpose of this pilot study was to test the feasibility and acceptability of a mindfulness-based program for low income , minority older adults provided in residence . The secondary purpose was to learn if the mindfulness-based program produced differences in blood pressure between the intervention and control groups . Participants were at least 62 years old and residents of a low-income senior residence . All participants were African-American , and one was male . Twenty participants were r and omized to the mindfulness-based intervention or a social support control group of the same duration and dose . Blood pressure was measured with the Omron automatic blood pressure machine at baseline and at the end of the 8-week intervention . A multivariate regression analysis was performed on the difference in scores between baseline and post-intervention blood pressure measurements , controlling for age , education , smoking status , and anti-hypertensive medication use . Effect sizes were calculated to quantify the magnitude of the relationship between participation in the mindfulness-based intervention and the outcome variable , blood pressure . Attendance remained > 80 % in all 8 weeks of both the intervention and the control groups . The average systolic blood pressure decreased for both groups post-intervention . Individuals in the intervention group exhibited a 21.92-mmHg lower systolic blood pressure compared to the social support control group post-intervention and this value was statistically significant ( p = 0.020 ) . The average diastolic blood pressure decreased in the intervention group post-intervention , but increased in the social support group . Individuals in the intervention group exhibited a 16.70-mmHg lower diastolic blood pressure compared to the social support group post-intervention , and this value was statistically significant ( p = 0.003 ) . Older adults are at a time in life when a reflective , stationary intervention , delivered in residence , could be an appealing mechanism to improve blood pressure . Given our preliminary results , larger trials in this hypertensive study population are warranted Context : Hypertension is a major chronic lifestyle disease . Several non-pharmacological interventions are effective in bringing down the blood pressure ( BP ) . This study focuses on the effectiveness of such interventions among young adults . Aims : To measure the efficacy of physical exercise , reduction in salt intake , and yoga , in lowering BP among young ( 20 - 25 ) pre-hypertensives and hypertensives , and to compare their relative efficacies . Setting s and Design : The study was done in the urban service area of JIPMER . Pre-hypertensives and hypertensives , identified from previous studies , constituted the universe . The participants were r and omized into one control and three interventional groups . Material s and Methods : A total of 113 subjects : 30 , 28 , 28 and 27 in four groups respectively participated for eight weeks : control ( I ) , physical exercise ( II ) - brisk walking for 50 - 60 minutes , four days/week , salt intake reduction ( III ) - to at least half of their previous intake , and practice of yoga ( IV ) - for 30 - 45 minutes/day on at least five days/week . Statistical Analysis Used : Efficacy was assessed using paired t test and ANOVA with Games Howell post hoc test . An intention to treat analysis was also performed . Results : A total of 102 participants ( 29 , 27 , 25 and 21 in groups I , II , III and IV ) completed the study . All three intervention groups showed a significant reduction in BP ( SBP/DBP : 5.3/6.0 in group II , 2.6/3.7 in III , and 2.0/2.6 mm Hg in IV respectively ) . There was no significant change ( SBP/DBP : 0.2/0.5 mmHg ) of BP in control group ( I ) . Physical exercise was most effective ( considered individually ) ; salt intake reduction and yoga were also effective . Conclusions : Physical exercise , salt intake reduction , and yoga are effective non-pharmacological interventions in significantly reducing BP among young hypertensives and pre-hypertensives . These can therefore be positively recommended for hypertensives . There is also a case to deploy these interventions in the general population OBJECTIVES Heart rate variability ( HRV ) reflects the integration of the parasympathetic nervous system with the rest of the body . Studies on the effects of yoga and exercise on HRV have been mixed but suggest that exercise increases HRV . We conducted a secondary analysis of the effect of yoga and exercise on HRV based on a r and omized clinical trial of treatments for vasomotor symptoms in peri/post-menopausal women . DESIGN R and omized clinical trial of behavioral interventions in women with vasomotor symptoms ( n=335 ) , 40 - 62 years old from three clinical study sites . INTERVENTIONS 12-weeks of a yoga program , design ed specifically for mid-life women , or a supervised aerobic exercise-training program with specific intensity and energy expenditure goals , compared to a usual activity group . MAIN OUTCOME MEASURES Time and frequency domain HRV measured at baseline and at 12 weeks for 15min using Holter monitors . RESULTS Women had a median of 7.6 vasomotor symptoms per 24h . Time and frequency domain HRV measures did not change significantly in either of the intervention groups compared to the change in the usual activity group . HRV results did not differ when the analyses were restricted to post-menopausal women . CONCLUSIONS Although yoga and exercise have been shown to increase parasympathetic-mediated HRV in other population s , neither intervention increased HRV in middle-aged women with vasomotor symptoms . Mixed results in previous research may be due to sample differences . Yoga and exercise likely improve short-term health in middle-aged women through mechanisms other than HRV BACKGROUND Emotional distress is an increasing public health problem and Hatha yoga has been cl aim ed to induce stress reduction and empowerment in practicing subjects . We aim ed to evaluate potential effects of Iyengar Hatha yoga on perceived stress and associated psychological outcomes in mentally distressed women . MATERIAL / METHODS A controlled prospect i ve non-r and omized study was conducted in 24 self-referred female subjects ( mean age 37.9+/-7.3 years ) who perceived themselves as emotionally distressed . Subjects were offered participation in one of two subsequential 3-months yoga programs . Group 1 ( n=16 ) participated in the first class , group 2 ( n=8 ) served as a waiting list control . During the yoga course , subjects attended two-weekly 90-min Iyengar yoga classes . Outcome was assessed on entry and after 3 months by Cohen Perceived Stress Scale , State-Trait Anxiety Inventory , Profile of Mood States , CESD-Depression Scale , Bf-S/Bf-S ' Well-Being Scales , Freiburg Complaint List and ratings of physical well-being . Salivary cortisol levels were measured before and after an evening yoga class in a second sample . RESULTS Compared to waiting-list , women who participated in the yoga-training demonstrated pronounced and significant improvements in perceived stress ( P<0.02 ) , State and Trait Anxiety ( P<0.02 and P<0.01 , respectively ) , well-being ( P<0.01 ) , vigor ( P<0.02 ) , fatigue ( P<0.02 ) and depression ( P<0.05 ) . Physical well-being also increased ( P<0.01 ) , and those subjects suffering from headache or back pain reported marked pain relief . Salivary cortisol decreased significantly after participation in a yoga class ( P<0.05 ) . CONCLUSIONS Women suffering from mental distress participating in a 3-month Iyengar yoga class show significant improvements on measures of stress and psychological outcomes . Further investigation of yoga with respect to prevention and treatment of stress-related disease and of underlying mechanism is warranted BACKGROUND Prolonged activation of the hypothalamus-pituitary-adrenal system is thought to have deleterious effects on brain function . Neuroendocrine studies suggest that brain exposure to higher cortisol concentrations contribute to cognitive deficits as we age . Mind-body techniques such as yoga have shown to improve stress levels by restoring the body 's sympathetic-parasympathetic balance . The objective of this study was to determine whether yoga practice moderated the stress response result ing in improved executive function . METHODS Sedentary community dwelling older adults ( N=118 , Mean age=62.02 ) were r and omized to an 8-week yoga intervention or a stretching control group . At baseline and following 8 weeks , all participants completed measures of executive function , self-reported stress and anxiety and provided saliva sample s before and after cognitive testing to assess cortisol . RESULTS Yoga participants showed improved accuracy on executive function measures and an attenuated cortisol response compared to their stretching counterparts who showed increased cortisol levels and poor cognitive performance at follow up . The change in cortisol levels as well as self-reported stress and anxiety levels predicted performance on the running span task , n-back working memory and task switching paradigm ( β's=0.27 - 0.38 , p's≤0.05 for yoga and β's=-0.37 - 0.47 , p's≤0.01 for stretching control ) . CONCLUSION Eight weeks of regular yoga practice result ed in improved working memory performance that was mediated by an attenuated response to stress as measured by self-report stress and objective salivary cortisol measurements . This trial offers evidence for non-traditional physical activity interventions such as yoga that may be helpful in restoring HPA balance in older adults , thereby preventing cognitive decline High blood pressure ( BP ) is a known risk factor for cardiovascular disease morbidity . Considering the growing evidence of nonpharmacological interventions in the management of high BP , we design ed a r and omized , parallel active-controlled study on the effect of yoga and st and ard lifestyle modification ( LSM ) on BP and heart rate in individuals with prehypertension ( systolic BP 120–139 mm Hg and /or diastolic BP 80–89 mm Hg ) . Volunteers ( 20–60 years ) of both genders without any known cardiovascular disease were r and omized into either LSM group ( n=92 ) or LSM+yoga group ( n=92 ) . Before the intervention , age , waist circumference , physical activity , BP and fasting plasma glucose and lipids were comparable between the groups . After 12 weeks of intervention , we observed a significant reduction in the BP and heart rate in both the groups . Further , the reduction in systolic BP was significantly more in LSM+yoga group ( 6 mm Hg ) as compared with LSM group ( 4 mm Hg ) . In addition , 13 prehypertensives became normotensives in LSM+yoga group and four in LSM group . The results indicate efficacy of nonpharmacological intervention and the additional benefit of yoga to st and ard LSM . Further research in this field may add to the level of evidence on the benefit of yoga , in the reduction of BP in high BP subjects , in the scientific literature It is unclear whether the age-associated reduction in baroreflex sensitivity is modifiable by exercise training . The effects of aerobic exercise training and yoga , a non-aerobic control intervention , on the baroreflex of elderly persons was determined . Baroreflex sensitivity was quantified by the alpha-index , at high frequency ( HF ; 0.15 - 0.35 Hz , reflecting parasympathetic activity ) and mid-frequency ( MF ; 0.05 - 0.15 Hz , reflecting sympathetic activity as well ) , derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure . Twenty-six ( 10 women ) sedentary , healthy , normotensive elderly ( mean 68 years , range 62 - 81 years ) subjects were studied . Fourteen ( 4 women ) of the sedentary elderly subjects completed 6 weeks of aerobic training , while the other 12 ( 6 women ) subjects completed 6 weeks of yoga . Heart rate decreased following yoga ( 69 + /- 8 vs. 61 + /- 7 min-1 , P < 0.05 ) but not aerobic training ( 66 + /- 8 vs. 63 + /- 9 min-1 , P = 0.29 ) . VO2 max increased by 11 % following yoga ( P < 0.01 ) and by 24 % following aerobic training ( P < 0.01 ) . No significant change in alpha MF ( 6.5 + /- 3.5 vs. 6.2 + /- 3.0 ms mmHg-1 , P = 0.69 ) or alpha HF ( 8.5 + /- 4.7 vs. 8.9 + /- 3.5 ms mmHg-1 , P = 0.65 ) occurred after aerobic training . Following yoga , alpha HF ( 8.0 + /- 3.6 vs. 11.5 + /- 5.2 ms mmHg-1 , P < 0.01 ) but not alpha MF ( 6.5 + /- 3.0 vs. 7.6 + /- 2.8 ms mmHg-1 , P = 0.29 ) increased . Short- duration aerobic training does not modify the alpha-index at alpha MF or alpha HF in healthy normotensive elderly subjects . alpha HF but not alpha MF increased following yoga , suggesting that these parameters are measuring distinct aspects of the baroreflex that are separately modifiable BACKGROUND Yoga/Stretching ( YS ) and functional resistance ( FR ) training are popular exercise routines . A protein-pacing ( PP ) diet is a common dietary regimen . Thus , we assessed the effectiveness of a PP diet alone and in combination with either YS or FR to improve body composition and cardiometabolic health . METHODS Twenty-seven overweight women ( age = 43.2 ± 4.6 years ) were r and omized into 3 groups : yoga ( YS , n = 8) or resistance ( FR , n = 10 ) training ( 3 days/week ) in conjunction with PP diet ( 50 % carbohydrate , 25 % protein , and 25 % fat ) or PP diet-only ( PP , n = 9 ) throughout 12-week study . PP maintained preexisting levels of physical activity . Body weight ( BW ) , total ( BF ) and abdominal ( ABF ) body fat , waist circumference ( WC ) , plasma biomarkers , and aerobic fitness ( VO2 ) were measured at baseline and 12 weeks . RESULTS WC and total cholesterol improved in all groups , whereas glycemia tended to improve ( P = .06 ) in S. BF , ABF , and VO2 increased significantly in YS and FR ( P < .05 ) . Feelings of vigor increased in YS and tension decreased in FR ( P < .05 ) . CONCLUSIONS YS training tended to decrease blood glucose compared with FR and PP and is equally effective at enhancing body composition , and aerobic fitness in overweight women providing a strong rationale for further research on YS training Aim : To study the effect of integrated yoga on pain , morning stiffness and anxiety in osteoarthritis of knees . Material s and Methods : Two hundred and fifty participants with OA knees ( 35–80 years ) were r and omly assigned to yoga or control group . Both groups had transcutaneous electrical stimulation and ultrasound treatment followed by intervention ( 40 min ) for two weeks with follow up for three months . The integrated yoga consisted of yogic loosening and strengthening practice s , asanas , relaxation , pranayama and meditation . The control group had physiotherapy exercises . Assessment s were done on 15th ( post 1 ) and 90th day ( post 2 ) . Results : Resting pain ( numerical rating scale ) reduced better ( P<0.001 , Mann – Whitney U test ) in yoga group ( post 1=33.6 % and post 2=71.8 % ) than control group ( post 1=13.4 % and post 2=37.5 % ) . Morning stiffness decreased more ( P<0.001 ) in yoga ( post 1=68.6 % and post 2=98.1 % ) than control group ( post 1=38.6 % and post 2=71.6 % ) . State anxiety ( STAI-1 ) reduced ( P<0.001 ) by 35.5 % ( post 1 ) and 58.4 % ( post 2 ) in the yoga group and 15.6 % ( post 1 ) and 38.8 % ( post 2 ) in the control group ; trait anxiety ( STAI 2 ) reduced ( P<0.001 ) better ( post 1=34.6 % and post 2=57.10 % ) in yoga than control group ( post 1=14.12 % and post 2=34.73 % ) . Systolic blood pressure reduced ( P<0.001 ) better in yoga group ( post 1=−7.93 % and post 2=−15.7 % ) than the control group ( post 1=−1.8 % and post 2=−3.8 % ) . Diastolic blood pressure reduced ( P<0.001 ) better in yoga group ( post 1=−7.6 % and post 2=−16.4 % ) than the control group ( post 1=−2.1 % and post 2=−5.0 % ) . Pulse rate reduced ( P<0.001 ) better in yoga group ( post 1=−8.41 % and post 2=−12.4 % ) than the control group ( post 1=−5.1 % and post 2=−7.1 % ) . Conclusion : Integrated approach of yoga therapy is better than physiotherapy exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in reducing pain , morning stiffness , state and trait anxiety , blood pressure and pulse rate in patients with OA knees Context : Breast cancer patients awaiting surgery experience heightened distress that could affect postoperative outcomes . Aims : The aim of our study was to evaluate the effects of yoga intervention on mood states , treatment-related symptoms , quality of life and immune outcomes in breast cancer patients undergoing surgery . Setting s and Design : Ninety-eight recently diagnosed stage II and III breast cancer patients were recruited for a r and omized controlled trial comparing the effects of a yoga program with supportive therapy plus exercise rehabilitation on postoperative outcomes following surgery . Material s and Methods : Subjects were assessed prior to surgery and four weeks thereafter . Psychometric instruments were used to assess self-reported anxiety , depression , treatment-related distress and quality of life . Blood sample s were collected for enumeration of T lymphocyte subsets ( CD4 % , CD8 % and natural killer ( NK ) cell % counts ) and serum immunoglobulins ( IgG , IgA and IgM ) . Statistical Analysis Used : We used analysis of covariance to compare interventions postoperatively . Results : Sixty-nine patients contributed data to the current analysis ( yoga n = 33 , control n = 36 ) . The results suggest a significant decrease in the state ( P = 0.04 ) and trait ( P = 0.004 ) of anxiety , depression ( P = 0.01 ) , symptom severity ( P = 0.01 ) , distress ( P < 0.01 ) and improvement in quality of life ( P = 0.01 ) in the yoga group as compared to the controls . There was also a significantly lesser decrease in CD 56 % ( P = 0.02 ) and lower levels of serum IgA ( P = 0.001 ) in the yoga group as compared to controls following surgery . Conclusions : The results suggest possible benefits for yoga in reducing postoperative distress and preventing immune suppression following surgery Background / Aims : The primary therapeutic goals in ulcerative colitis ( UC ) are to maintain excellent quality of life ( QOL ) by treating flare-ups when they occur , and preventing flare-ups . Since stress can trigger UC flare-ups , we investigated the efficacy of mindfulness-based stress reduction ( MBSR ) to reduce flare-ups and improve QOL . Methods : Patients with moderately severe UC , in remission , were r and omized to MBSR or time/attention control . Primary outcome was disease status . Secondary outcomes were changes in markers of inflammation and disease activity , markers of stress and psychological assessment s. Results : 55 subjects were r and omized . Absence of flares , time to flare and severity of flare over 1 year were similar between the two groups . However , post hoc analysis showed that MBSR decreased the proportion of participants with at least one flare-up among those with top tertile urinary cortisol and baseline perceived stress ( 30 vs. 70 % ; p < 0.001 ) . MBSR patients who flared demonstrated significantly lower stress at the last visit compared to flared patients in the control group ( p = 0.04 ) . Furthermore , MBSR prevented a drop in the Inflammatory Bowel Disease Quality of Life Question naire during flare ( p < 0.01 ) . Conclusion : MBSR did not affect the rate or severity of flare-ups in UC patients in remission . However , MBSR might be effective for those with high stress reactivity ( high perceived stress and urinary cortisol ) during remission . MBSR appears to improve QOL in UC patients by minimizing the negative impact of flare-ups on QOL . Further studies are needed to identify a subset of patients for whom MBSR could alter disease course BACKGROUND In 2012 , yoga was practice d by 20 million Americans , of whom 82 % were women . A recent literature review on prenatal yoga noted a reduction in some pregnancy complications ( ie , preterm birth , lumbar pain , and growth restriction ) in those who practice d yoga ; to date , there is no evidence on fetal response after yoga . OBJECTIVES We aim ed to characterize the acute changes in maternal and fetal response to prenatal yoga exercises using common st and ardized tests to assess the well-being of the maternal-fetal unit . STUDY DESIGN We conducted a single , blinded , r and omized controlled trial . Uncomplicated pregnancies between 28 0/7 and 36 6/7 weeks with a nonanomalous singleton fetus of women who did not smoke , use narcotics , or have prior experience with yoga were included . A computer-generated simple r and omization sequence with a 1:1 allocation ratio was used to r and omize participants into the yoga or control group . Women in the yoga group participated in a 1-time , 1 hour yoga class with a certified instructor who taught a predetermined yoga sequence . In the control group , each participant attended a 1-time , 1 hour PowerPoint presentation by an obstetrician on American Congress of Obstetricians and Gynecologists recommendations for exercise , nutrition , and obesity in pregnancy . All participants underwent pre- and postintervention testing , which consisted of umbilical and uterine artery Doppler ultrasound , nonstress testing , a biophysical profile , maternal blood pressure , and maternal heart rate . A board-certified maternal-fetal medicine specialist , at a different tertiary center , interpreted all nonstress tests and biophysical profile data and was blinded to group assignment and pre- or postintervention testing . The primary outcome was a change in umbilical artery Doppler systolic to diastolic ratio . Sample size calculations indicated 19 women per group would be sufficient to detect this difference in Doppler indices ( alpha , 0.05 ; power , 80 % ) . Data were analyzed using a repeated- measures analysis of variance , a χ(2 ) , and a Fisher exact test . A value of P < .05 was considered significant . RESULTS Of the 52 women r and omized , 46 ( 88 % ) completed the study . There was no clinical ly significant change in umbilical artery systolic to diastolic ratio ( P = .34 ) , pulsatility index ( P = .53 ) , or resistance index ( P = .66 ) between the 2 groups before and after the intervention . Fetal and maternal heart rate , maternal blood pressure , and uterine artery Dopplers remained unchanged over time . When umbilical artery indices were individually compared with gestational age references , there was no difference between those who improved or worsened between the groups . CONCLUSION There was no significant change in fetal blood flow acutely after performing yoga for the first time in pregnancy . Yoga can be recommended for low-risk women to begin during pregnancy OBJECTIVES To evaluate effects of Hatha yoga and Omkar meditation on cardiorespiratory performance , psychologic profile , and melatonin secretion . SUBJECTS AND METHODS Thirty healthy men in the age group of 25 - 35 years volunteered for the study . They were r and omly divided in two groups of 15 each . Group 1 subjects served as controls and performed body flexibility exercises for 40 minutes and slow running for 20 minutes during morning hours and played games for 60 minutes during evening hours daily for 3 months . Group 2 subjects practice d selected yogic asanas ( postures ) for 45 minutes and pranayama for 15 minutes during the morning , whereas during the evening hours these subjects performed preparatory yogic postures for 15 minutes , pranayama for 15 minutes , and meditation for 30 minutes daily , for 3 months . Orthostatic tolerance , heart rate , blood pressure , respiratory rate , dynamic lung function ( such as forced vital capacity , forced expiratory volume in 1 second , forced expiratory volume percentage , peak expiratory flow rate , and maximum voluntary ventilation ) , and psychologic profile were measured before and after 3 months of yogic practice s. Serial blood sample s were drawn at various time intervals to study effects of these yogic practice s and Omkar meditation on melatonin levels . RESULTS Yogic practice s for 3 months result ed in an improvement in cardiorespiratory performance and psychologic profile . The plasma melatonin also showed an increase after three months of yogic practice s. The systolic blood pressure , diastolic blood pressure , mean arterial pressure , and orthostatic tolerance did not show any significant correlation with plasma melatonin . However , the maximum night time melatonin levels in yoga group showed a significant correlation ( r = 0.71 , p < 0.05 ) with well-being score . CONCLUSION These observations suggest that yogic practice s can be used as psychophysiologic stimuli to increase endogenous secretion of melatonin , which , in turn , might be responsible for improved sense of well-being The purpose of this study was to compare the effects of Korean mindfulness-based stress reduction ( K-MBSR ) , walking , and patient education regarding diabetes mellitus ( DM ) on stress response , glycemic control , and vascular inflammation in patients with diabetes mellitus . A cluster r and omized trial including 56 adults with diabetes mellitus ( K-MBSR group = 21 , walking group = 18 , patient education group = 17 ) was conducted between 13 July and 14 September 2012 . The question naire included the Diabetes Distress Scale and Perceived Stress Response Inventory . Fasting blood sample s were used to measure levels of cortisol , blood glucose , plasminogen activator inhibitor-1 ( PAI-1 ) , and tissue plasminogen activator ( t-PA ) . There were no statistically significant differences between the effects of K-MBSR , walking , and patient education on stress , glycemic control , or vascular inflammation . However , in the K-MBSR and walking groups , significant reductions in the levels of serum cortisol and PAI-1 were observed . A significant reduction in psychological responses to stress was observed in the walking and patient education groups . Longitudinal studies could provide better insight into the impact of K-MBSR , walking , and patient education on health outcomes in adults with diabetes mellitus OBJECTIVE We aim ed to determine the effect of yoga on arterial function in elderly with increased pulse pressure ( PP ) . DESIGN R and omized controlled study with two parallel groups . PARTICIPANTS Elderly subjects with PP≥60 mmHg ( n=60 ) . INTERVENTIONS Yoga group ( n=30 ) was assigned for yoga training and brisk-walking ( BW ) group ( n=30 ) for brisk-walk with stretching exercise for 1h in the morning for 6 days in a week for 12 weeks . MAIN OUTCOME MEASURES Arterial stiffness measures : Brachial-ankle pulse wave velocity ( baPWV ) , Carotid-femoral pulse wave velocity ( c-f PWV ) , aortic augmentation index ( AIx@75 ) , arterial stiffness index at brachial ( bASI ) and tibial arteries ( aASI ) . Total serum nitric oxide concentration ( NOx ) as an index of endothelial function . Heart rate variability ( HRV ) measures : Low frequency and high frequency in normalized units ( LFnu , HFnu ) and LF/HF ratio . RESULTS The mean between-group change ( with 95 % CI ) in arterial stiffness : c-f PWV(m/s ) [ 1.25(0.59 - 1.89 ) ; p<0.001 ] , baPWV(m/s ) [ 1.96(0.76 - 3.16 ) , p<0.01 ] , AIx@75 [ 3.07(0.24 - 5.89 ) , p=0.066 ] , aASI [ 8.3(4.06 - 12.53 ) , p<0.001 ] ; endothelial function index : NO(μmol/L ) [ -9.03(-14.57 to -3.47 ) , p<0.001 ] ; SBP(mmHg ) [ 14.23(12.03 - 16.44 ) , p<0.001 ] , DBP(mmHg ) [ 0.1(-1.95 - 2.15 ) , p=0.38 ] , PP(mmHg ) [ 14.07(11.2 - 16.92 ) , p<0.001 ] , MAP(mmHg ) [ 4.7(3.08 - 6.32 ) , p<0.001 ] ; and cardiac autonomic function : LF(nu ) [ 4.81(1.54 - 8.08 ) , p<0.01 ] , HF(nu ) [ -4.13(-7.57 to -0.69 ) , p<0.01 ] , LF/HF ratio [ 0.84(0.3 - 1.37 ) , p<0.001 ] , indicate significant difference in effects of two intervention on arterial stiffness , endothelial function , BP and cardiac autonomic activity . There was significant change within-yoga group in vascular function , BP and autonomic function , while no significant change within-BW group was observed . CONCLUSION Our findings suggest that yoga program offered was more effective than brisk-walk in reducing arterial stiffness along with BP in elderly individuals with increased PP . Yoga can also significantly reduce sympathetic activity and improve endothelial function with enhancement in bioavailability of NO The purpose of this study was to compare the effects of yoga with an active control ( nonaerobic exercise ) in individuals with prehypertension and stage 1 hypertension . A r and omized clinical trial was performed using two arms : ( 1 ) yoga and ( 2 ) active control . Primary outcomes were 24-hour day and night ambulatory systolic and diastolic blood pressures . Within-group and between-group analyses were performed using paired t tests and repeated- measures analysis of variance ( time × group ) , respectively . Eighty-four participants enrolled , with 68 participants completing the trial . Within-group analyses found 24-hour diastolic , night diastolic , and mean arterial pressure all significantly reduced in the yoga group ( -3.93 , -4.7 , -4.23 mm Hg , respectively ) but no significant within-group changes in the active control group . Direct comparisons of the yoga intervention with the control group found a single blood pressure variable ( diastolic night ) to be significantly different ( P=.038 ) . This study has demonstrated that a yoga intervention can lower blood pressure in patients with mild hypertension . Although this study was not adequately powered to show between-group differences , the size of the yoga-induced blood pressure reduction appears to justify performing a definitive trial of this intervention to test whether it can provide meaningful therapeutic value for the management of hypertension BACKGROUND Mindfulness meditation training interventions have been shown to improve markers of health , but the underlying neurobiological mechanisms are not known . Building on initial cross-sectional research showing that mindfulness meditation may increase default mode network ( DMN ) resting-state functional connectivity ( rsFC ) with regions important in top-down executive control ( dorsolateral prefrontal cortex [ dlPFC ] ) , here we test whether mindfulness meditation training increases DMN-dlPFC rsFC and whether these rsFC alterations prospect ively explain improvements in interleukin (IL)-6 in a r and omized controlled trial . METHODS Stressed job-seeking unemployed community adults ( n = 35 ) were r and omized to either a 3-day intensive residential mindfulness meditation or relaxation training program . Participants completed a 5-minute resting-state scan before and after the intervention program . Participants also provided blood sample s at preintervention and at 4-month follow-up , which were assayed for circulating IL-6 , a biomarker of systemic inflammation . RESULTS We tested for alterations in DMN rsFC using a posterior cingulate cortex seed-based analysis and found that mindfulness meditation training , and not relaxation training , increased posterior cingulate cortex rsFC with left dlPFC ( p < .05 , corrected ) . These pretraining to posttraining alterations in posterior cingulate cortex-dlPFC rsFC statistically mediated mindfulness meditation training improvements in IL-6 at 4-month follow-up . Specifically , these alterations in rsFC statistically explained 30 % of the overall mindfulness meditation training effects on IL-6 at follow-up . CONCLUSIONS These findings provide the first evidence that mindfulness meditation training functionally couples the DMN with a region known to be important in top-down executive control at rest ( left dlPFC ) , which , in turn , is associated with improvements in a marker of inflammatory disease risk |
2,136 | 25,247,520 | Devices integrated into the care delivery system and design ed to record dosing events are most frequently associated with improved adherence , compared with other devices . | IMPORTANCE Medication nonadherence , which has been estimated to affect 28 % to 31 % of US patients with hypertension , hyperlipidemia , and diabetes , may be improved by electronic medication packaging ( EMP ) devices ( adherence-monitoring devices incorporated into the packaging of a prescription medication ) .
OBJECTIVES To investigate whether EMP devices are associated with improved adherence and to identify and describe common features of EMP devices .
CONCLUSIONS AND RELEVANCE Many varieties of EMP devices exist . | OBJECTIVE : To compare adherence data from an electronic medication-event monitoring device ( MEMS , Aprex ) with pill counts in assisting pharmacists in making recommendations regarding diabetes therapy . DESIGN : Two-month , double-blind , r and omized , controlled trial . SETTING : Veterans Affairs Medical Center ambulatory care clinics . PATIENTS : Forty-seven patients with poor to fair metabolic control of diabetes mellitus were enrolled . Patients were excluded if they were receiving insulin , had a concurrent infection , required child-resistant caps or medication reminder devices , or could not return for follow-up visits . Twenty patients were r and omized to the MEMS and 27 to the control group ( pill counts ) . Fasting plasma glucose concentrations were measured monthly and glycohemoglobin concentrations were measured at baseline and 60 days . Thirty-two patients were evaluable : 15 using MEMS and 17 using pill counts . INTERVENTION : Investigators made pharmacologic or educational recommendations to the patient 's healthcare provider based on both laboratory data and MEMS readings in the treatment group or laboratory data and pill counts in the control group . MAIN OUTCOME MEASURE : Quantities and types of recommendations regarding diabetes therapy made by pharmacists using adherence data from the two methods were tabulated . RESULTS : In the MEMS group , 47 percent of the recommendations related to patient education compared with 12 percent in the control group ( p=0.028 ) . MEMS data would have changed four recommendations in the control group to involve patient education . CONCLUSIONS : MEMS data result ed in different numbers and types of recommendations than pill counts . Pharmacists then could make specific recommendations regarding patient education before resorting to pharmacologic manipulations This study examined the role of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance within a r and omized trial of bupropion-SR for smoking cessation . Female participants ( N = 97 ) received MEMS bottles containing bupropion-SR 150 mg or placebo , to be taken twice daily . A r and omly selected “ feedback ” group of participants was told about the recording device in the bottle cap and received weekly graphic feedback showing their pill-taking behavior with specific instructions for improving compliance . A “ no-feedback ” group was not informed about the MEMS bottles , and did not receive further instruction or feedback beyond the st and ard dosing instructions . Compliance outcomes were the total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the feedback group . Participation in the feedback group predicted higher compliance beyond demographic , smoking , and health belief variables , suggesting significant benefit in providing brief feedback and instruction throughout the medication regimen Objective The goal of this study was to evaluate clinical ly the acceptability of the IDAS II ( Intelligent Drug Administration System ) , a new electronic device that enables drug adherence monitoring . Methods IDAS II was compared to another electronic monitor , the Medication Event Monitoring System ( MEMS ) in a r and omised two-way cross-over study involving 24 hypertensive patients treated with irbesartan . Patients used each device for 2 months . The main parameter of evaluation was the patients ’ opinion on both devices . Rates of adherence and blood pressure were also assessed . Results Most patients considered both devices to be reliable reminders ( IDAS II : 75%;MEMS : 84 % , p = ns ) . Ten patients ( 42 % ) preferred the MEMS , while 11 ( 46 % ) preferred the IDAS II ; three ( 12 % ) expressed no preference . Patients found the MEMS device easier to use than the IDAS device ( p < 0.001 ) but appreciated the IDAS blister packs better than the MEMS bulk packaging ( p < 0.01 ) . Over the 4-month period , the median “ taking adherence ” was excellent ( 99.2 % ) and comparable with both devices . However , the regularity of drug intake timing was higher with the IDAS II ( p < 0.01 ) . Conclusion IDAS II , a new electronic device enabling drug adherence monitoring without reconditioning of the drugs appears to be a well-accepted device . Overall , practicability and acceptability of the IDAS II and the MEMS device were similar . Thus , IDAS II could be a useful tool for the management of long-term therapies Background and Objectives : Older adults ' adherence to antihypertensive medications is far lower than what is considered necessary for clinical effectiveness , despite the risks for adverse cardiovascular events from uncontrolled blood pressure ( BP ) in the elderly . This pilot study tested a novel 8-week behavioral feedback intervention to improve antihypertensive medication adherence ( MA ) and BP control among older adults on existing treatment for hypertension . Methods : Adults 60 years old , or older taking at least 1 antihypertensive medication were r and omized to receive the nurse-delivered adherence intervention or usual care . Medication adherence was monitored continuously using electronic monitoring for 20 weeks . Intervention-group participants received biweekly MA and BP feedback , habit counseling , medication and disease education , a medication instruction card , and were given an electronic medication bottle cap with a digital display that provided daily adherence feedback during the 8-week intervention . Blood pressure was measured by a nurse at 12 and 20 weeks after r and omization . Adherence and BP outcomes were described using descriptive statistics and analyzed for between- and within-group differences using Mann-Whitney U tests . Results : Fifteen participants ( median age , 71 years ; 73 % female ) were eligible for r and omization . Participants took an average of 5.8 prescription medications and 2.93 over-the-counter medications per day . A nonsignificant difference was noted in baseline MA between groups . At the end of the intervention , the treatment group had better antihypertensive MA than did the control group ( median MA : 100 % vs 27.3 % , U = 5.00 , P = .013 ) . Systolic BP improved slightly in the intervention group during the study and was significantly different at week 12 ( median systolic BP : 130 vs 152 mm Hg ; U = 4.50 , P = .008 ) . Diastolic BP was largely unchanged over the course of the study . Conclusion : The results indicate that the intervention had a positive effect on MA . Additional testing is needed to further evaluate the intervention and its effect on adherence behavior and BP control Background Innovative approaches are needed to support patients ' adherence to drug therapy . The Real Time Medication Monitoring ( RTMM ) system offers real time monitoring of patients ' medication use combined with short message service ( SMS ) reminders if patients forget to take their medication . This combination of monitoring and tailored reminders provides opportunities to improve adherence . This article describes the design of an intervention study aim ed at evaluating the effect of RTMM on adherence to oral antidiabetics . Methods / Design R and omised Controlled Trial ( RCT ) with two intervention arms and one control arm involving diabetes type 2 patients with suboptimal levels of adherence to oral antidiabetics ( less than 80 % based on pharmacy refill data ) . Patients in the first intervention arm use RTMM including SMS reminders and a personal webpage where they can monitor their medication use . Patients in the second intervention arm use RTMM without SMS reminders or webpage access . Patients in the control arm are not exposed to any intervention . Patients are r and omly assigned to one of the three arms . The intervention lasts for six months . Pharmacy refill data of all patients are available from 11 months before , until 11 months after the start of the intervention . Primary outcome measure is adherence to oral antidiabetics calculated from : 1 ) data collected with RTMM , as a percentage of medication taken as prescribed , and as percentage of medication taken within the correct time interval , 2 ) refill data , taking the number of days for which oral antidiabetics are dispensed during the study period divided by the total number of days of the study period . Differences in adherence between the intervention groups and control group are studied using refill data . Differences in adherence between the two intervention groups are studied using RTMM data . Discussion The intervention described in this article consists of providing RTMM to patients with suboptimal adherence levels . This system combines real time monitoring of medication use with SMS reminders if medication is forgotten . If RTMM proves to be effective , it can be considered for use in various patient population s to support patients with their medication use and improve their adherence . Trial registration Netherl and s Trial Register Russell C , Conn V , Ashbaugh C , Madsen R , Wakefield M , Webb A , Coffey D , Peace L. Taking immunosuppressive medications effectively ( TIMELink ) : a pilot r and omized controlled trial in adult kidney transplant recipients . Clin Transplant 2011 : 25 : 864–870 . © 2010 John Wiley & Sons This pilot study aim ed to examine the effectiveness of visual-feedback therapy for individuals with psychotic disorders . Visual-feedback therapy combines structured psychodynamic therapy and visual feedback achieved via an electronic monitoring medication cap to increase insight about medication behaviours . Thirty subjects were r and omly assigned either to visual feedback or to a supportive counselling group . Medication adherence was measured by both electronic monitoring and blood plasma drug concentration levels . The results showed that , at the end of the 3-month , intervention ( bimonthly sessions ) , adherence rates of the visual-feedback group slightly increased , but declined during the course of the study for the supportive counselling control group ( P=0.026 ) Background / Aims . One of the causes of uncontrolled secondary hyperparathyroidism ( sHPT ) is patient 's poor drug adherence . We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet . Methods . Prospect i ve , r and omized , controlled , multicenter , open-label study . Fifty hemodialysis patients on a stable dose of cinacalcet were r and omized to an integrated care approach ( IC ) or usual care approach ( UC ) . In the IC group , cinacalcet adherence was monitored using an electronic system . Results were discussed with the patients in motivational interviews , and drug prescription adapted accordingly . In the UC group , drug adherence was monitored , but results were not available . Results . At six months , 84 % of patients in the IC group achieved recommended iPTH targets versus 55 % in the UC group ( P = 0.04 ) . The mean cinacalcet taking adherence improved by 10.8 % in the IC group and declined by 5.3 % in the UC group ( P = 0.02 ) . Concomitantly , the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group ( P = 0.03 ) . Conclusions . The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet PURPOSE To investigate the impact of an intervention program to improve adherence with topical , once daily therapy for glaucoma . DESIGN R and omized controlled clinical trial . PARTICIPANTS Sixty-six patients with glaucoma being treated with a prostagl and in analog in 1 or both eyes at the Scheie Eye Institute or Wilmer Eye Institute between November 2006 and June 2007 . METHODS In an observational study , participants who took 75 % or fewer doses ( as measured using the travoprost Dosing Aid [ DA ] ) during an initial 3-month period were r and omized into 2 groups . The intervention group watched an educational video , review ed current barriers to drop-taking and possible solutions with a study coordinator , received regular phone call reminders , and had audible and visible reminders activated on their DA devices . The control group was told to take drops as prescribed and received no additional intervention . MAIN OUTCOME MEASURES Change in drop use adherence as determined by the DA device . RESULTS In the 3-month observation period before r and omization , intervention group patients had used a mean of 54+/-17 % of scheduled doses , and this increased to 73+/-22 % during the following 3-month period ( P<0.001 , n = 35 ) . The control mean adherence rate of 46+/-23 % at baseline was statistically unchanged during the follow-up observation period ( 51+/-30 % , P = 0.16 , n = 31 ) . In a multivariate analysis , intervention , baseline compliance rate of < 50 % , and white ethnicity were predictors of improved adherence during the 3 months of intervention . The intraocular pressure ( IOP ) of the intervention and control groups did not change between months 3 and 6 after intervention ( P = 0.96 , 0.34 , respectively ) , and there was no correlation of IOP change with adherence rate change between both groups ( Pearson correlation r = 0.06 , P = 0.51 ) . CONCLUSIONS A multifaceted intervention significantly increased adherence with glaucoma medications . Those with improved adherence were in the intervention group , had very low adherence rates at baseline , and were white . IOP did not correlate with adherence . Further research is needed to determine which components of this intervention were most effective A two-group r and omized experimental design was employed to assess the effects of monitoring and feedback on the compliance of 93 psychiatric out patients treated with lithium . Compliance in both groups was measured using self-report , lithium level , appointment-keeping , and medication refill frequency . The experimental group was also monitored using a unique electronic device that records the time and day pills are removed . At the midpoint of the study , the experimental group received feedback about serum lithium levels and patterns of removing medications from the monitoring device while the control group received feedback about serum lithium levels only . The study demonstrated no sustained effect of the monitoring and feedback interventions on compliance BACKGROUND Medications can improve the functioning and health-related quality of life of patients with chronic heart failure ( CHF ) and reduce morbidity , mortality , and costs of treatment . However , patients may not adhere to therapy . Patients with complex medication regimens and low health literacy are at risk for nonadherence . OBJECTIVE The primary goal of this project is to develop and assess a multilevel pharmacy-based program to improve patient medication adherence and health outcomes for elderly CHF patients with low health literacy . METHODS In this 4-year , controlled trial , patients aged 50 years with a diagnosis of CHF who are being treated at Wishard Health Services ( Indianapolis , Indiana ) are r and omly assigned to pharmacist intervention or usual care . Intervention patients receive 9 months of pharmacist support and 3 months of postintervention follow-up . The intervention involves a pharmacist providing verbal and written education , icon-based labeling of medication containers , and therapeutic monitoring . The pharmacist identifies patients ' barriers to appropriate drug use , coaches them on overcoming these barriers , and coordinates medication use issues with their primary care providers . Daily up date s of relevant monitoring data are delivered via an electronic medical record system and stored in a personal computer system design ed to support pharmacist monitoring and facilitate documentation of interventions . To measure medication adherence objective ly , electronic monitoring lids are used on all CHF medications for patients in both study groups . Other assessment s include self-reported medication adherence , results of echocardiography ( eg , ejection fraction ) , brain natriuretic peptide concentrations , and health-related quality of life . Health services utilization , refill adherence , and cost data derive from electronic medical records . After completion of this study , the data can be used to assess the effectiveness and cost-effectiveness of our intervention . RESULTS One hundred twenty-two patients have been assigned to receive the intervention and 192 to receive usual care . CONCLUSIONS Our study aims to improve patients ' knowledge and self-management of their medication and to improve medication monitoring in a multilevel pharmacy-based intervention . By doing so , we intend that the intervention will improve the health outcomes of elderly patients with CHF Effective antiretroviral therapy ( ART ) requires excellent adherence . Little is known about how to improve ART adherence in many HIV/AIDS-affected countries , including China . We therefore assessed an adherence intervention among HIV-positive patients in southwestern China . Eighty subjects were enrolled and monitored for 6 months . Sixty-eight remaining subjects were r and omized to intervention/control arms . In months 7–12 , intervention subjects were counseled using EDM feedback ; controls continued with st and ard of care . Among r and omized subjects , mean adherence and CD4 count were 86.8 vs. 83.8 % and 297 vs. 357 cells/μl in intervention vs. control subjects , respectively . At month 12 , among 64 subjects who completed the trial , mean adherence had risen significantly among intervention subjects to 96.5 % but remained unchanged in controls . Mean CD4 count rose by 90 cells/μl and declined by 9 cells/μl among intervention and control subjects , respectively . EDM feedback as a counseling tool appears promising for management of HIV and other chronic diseases This study was conducted to replicate and extend initial positive findings on the usefulness of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance with bupropion for smoking cessation . Participants ( N=55 ) received MEMS bottles containing bupropion-SR ( 150 mg ) to be taken twice daily for 7 weeks . For participants r and omly assigned to the Enhanced Therapy group ( n=27 ) , weekly individual smoking cessation therapy sessions included an additional 10 min of MEMS feedback and compliance enhancement counseling using CBT techniques . The Usual Care group ( n=28 ) received weekly individual smoking cessation sessions only . Compliance outcomes included total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the Enhanced Therapy group . Smoking abstinence rates did not differ between the two groups , although results from the pooled sample analysis showed a significant association between level of medication compliance and abstinence status at treatment weeks 3 and 6 . Incorporating MEMS-based compliance interventions into smoking pharmacotherapy trials is recommended BACKGROUND Medication nonadherence contributes to hospitalization and mortality , yet there have been few interventions tested that improve adherence and reduce hospitalization and mortality in heart failure ( HF ) . Our objective was to determine whether an education intervention improved medication adherence and cardiac event-free survival . METHODS AND RESULTS A r and omized controlled trial was conducted on 82 HF patients . The intervention was based on the theory of planned behavior ( TPB ) and included feedback of medication-taking behavior using the Medication Event Monitoring System ( MEMS ) . Patients were assigned to one of three groups : 1 ) theory-based education plus MEMS feedback ; 2 ) theory-based education only ; or 3 ) usual care ( control ) . Cardiac events were collected for 9 months . Patients in both intervention groups were more adherent over follow-up compared with the control group . In Cox regression , patients in either intervention group had a longer event-free survival compared with those in the control group before and after controlling age , marital status , financial status , ejection fraction , New York Heart Association functional class , angiotensin-converting enzyme inhibitor use , and presence or absence of a significant other during the intervention ( P < .05 ) . CONCLUSIONS Use of an intervention based on the TPB improves medication adherence and outcomes in patients with HF and therefore offers promise as a clinical ly applicable intervention to help patients with HF to adhere to their prescribed regimen Background : Lipid-lowering treatment with statins has proven to be effective in reducing cardiovascular events and mortality . In daily practice , however , adherence to medication is often low and this compromises the therapeutic effect . The aim of this study was to assess the effectiveness of an electronic reminder device ( ERD ) with or without counseling to improve refill adherence and persistence for statin treatment in non-adherent patients . Methods : A multicenter , community pharmacy-based , r and omized controlled trial was conducted in 24 pharmacies in the Netherl and s among patients with pre-baseline refill adherence rates between 50 and 80 % . Eligible patients aged 65 years or older were r and omly assigned to 1 of 3 groups : ( 1 ) counseling with an ERD ( n = 134 ) , ( 2 ) ERD with a written instruction ( n = 131 ) , and a ( 3 ) control group that received the usual treatment ( n = 134 ) . Main outcome measure : refill adherence to statin treatment for a 360-day period after inclusion ( PDC360 ) . Patients with a refill rate ≥80 % were considered adherent . The effect among subgroups was also assessed . Results : There were no relevant differences at baseline . In the counseling with ERD group 54 of 130 eligible patients received the counseling with ERD . In the ERD group , 117 of 123 eligible patients received the ERD . The proportions of adherent patients in the counseling with ERD-group ( 69.2 % ) and in the ERD group ( 72.4 % ) were not higher than in the control group ( 64.8 % ) . Among women using statins for secondary prevention , more patients were adherent in the ERD group ( 86.1 % ) than in the control group ( 52.6 % ) ( p < 0.005 ) . In men using statins for secondary prevention the ERD was found to have no effect . Conclusion : In this r and omized controlled trial , no statistically significant improvement of refill adherence was found if an ERD was used with or without counseling . However , in a subgroup of women using statins for secondary prevention the ERD did improve adherence significantly OBJECTIVE To assess the feasibility and efficacy of two interventions for improving adherence to antiretroviral therapy regimens in HIV-infected subjects compared with a control intervention . DESIGN R and omized , controlled , pilot study . SETTING Department of Veterans Affairs HIV clinic and community-based HIV clinical trials site . PARTICIPANTS Fifty-five HIV-infected subjects on stable antiretroviral therapy regimens . Subjects were predominantly male ( 89 % ) and African American ( 69 % ) , and had histories of heroin or cocaine use ( 80 % ) . INTERVENTIONS Four weekly sessions of either nondirective inquiries about adherence ( control group , C ) , cue-dose training , which consisted of the use of personalized cues for remembering particular dose times , and feedback about medication taking using Medication Event Monitoring System ( MEMS ) pill bottle caps , which record time of bottle opening ( CD group ) , or cue-dose training combined with cash reinforcement for correctly timed bottle opening ( CD+CR ) . MEASUREMENTS Opening of the pill bottle within 2 hours before or after a predetermined time was measured by MEMS . RESULTS Adherence to the medication as documented by MEMS was significantly enhanced during the 4-week training period in the CD+CR group , but not in the CD group , compared with the control group . Improvement was also seen in adherence to antiretroviral drugs that were not the object of training and reinforcement . Eight weeks after training and reinforcement were discontinued , adherence in the cash-reinforced group returned to near-baseline levels . CONCLUSIONS Cue-dose training with cash reinforcement led to transient improvement in adherence to antiretroviral therapy in a population including mostly African Americans and subjects with histories of drug abuse . However , we were not able to detect any sustained improvement beyond the active training period , and questions concerning the timing and duration of such an intervention require further study . R and omized , controlled clinical studies with objective measures of adherence can be conducted in HIV-infected subjects and should be employed for further evaluation of this and other adherence interventions Abstract PURPOSE : Electronic-monitored adherence is often used as the primary outcome measure for evaluating adherence interventions . However , electronic monitoring may not only measure adherence , but may also improve or impede adherence , making it difficult to assess the extent to which the observed effect size is attributed to the intervention versus electronic monitoring . This study examined whether electronic monitoring and patient diaries alter as well as measure adherence . METHOD : A sample of 180 patients on highly active antiretroviral therapy ( HAART ) were r and omized to one of three adherence surveillance methods ( electronic monitoring caps , patient medication diaries , no surveillance control group ) for 4 weeks , with adherence measured by a structured interview at baseline and study endpoint ; 173 ( 96 % ) participants completed the study . RESULTS : After controlling for baseline adherence , a univariate analyses of adherence at study endpoint revealed no significant differences across groups , F(2 , 169 ) = 0.32 , p = .73 , with mean adherence rates of 91.4 , 92.4 , and 93.8 for the electronic monitoring , diaries , and control group , respectively . Similarly , the proportion of participants with good adherence ( ≥95 % ) did not differ significantly from baseline to week 4 among all three subgroups . CONCLUSION : These results suggest that electronic monitoring caps and medication diaries do not alter adherence and can be used as outcome measures of interventions without the need to adjust the observed effect size Electronic caps , pill caps that record the date and time of pill bottle opening provide an objective measure of adherence to prescribed medication . A promising intervention to improve adherence , cue-dose training , involves review ing patients ' pill cap-generated reports concerning their medication-taking and offering individualized recommendations for remembering to take medications at specific times of day . In this preliminary study , 79 patients prescribed the antihyperglycemic medication metformin had adherence assessed during a 4-week baseline period . Adherence , defined as proportion of prescribed doses taken within a predetermined 4-h window , was measured using electronic MEMS caps . Those who had less than 80 % baseline adherence ( n = 33 ) were r and omly assigned to either receive 4 months of cue-dose training ( n = 16 ) or to a control group ( n = 17 ) . Cue-dose training was associated with significantly better adherence to metformin ( mean improvement of 15 % ) . The effects of cue-dose training on adherence to other antihyperglycemic medication did not reach statistical significance . Glycosylated hemoglobin ( a measure of blood sugar control ) did not differ between groups . Data from nine patients who review ed pill cap-generated data with their primary care providers suggested that both patients and providers found the discussion moderately helpful and not at all uncomfortable A two-phase study was conducted to assess the effect of an electronic medication compliance aid on hypertension control and pharmaceutical compliance in ambulatory patients . In Phase I ( 12 weeks ) , 36 patients were r and omly assigned to a medication vial equipped with a cap containing a digital timepiece that displays the last time the cap was removed . The control group included 34 patients r and omly assigned to a st and ard medication vial . Subjects using the timepiece cap showed an average compliance rate of 95.1 % , an average decrease in systolic pressure of 7.6 mm Hg ( P = .006 ) , and an average decrease in diastolic pressure of 8.8 mm Hg ( P less than .001 ) . Controls had an average compliance rate of 78 % and decreases of 2.8 mm Hg and 0.2 mm Hg in systolic and diastolic pressures , respectively . Phase II ( 12 weeks ) combined use of the timepiece cap with other compliance aids : a pocket-size card for recording blood pressure and a blood pressure cuff for self-monitoring . Patients using the timepiece cap and the card had an average compliance rate of 98.7 % with mean decreases of 11 mm Hg in systolic pressure ( P less than .01 ) and 7.64 Hg mm in diastolic pressure ( P = .0001 ) . The combined use of the cap , the card , and the blood pressure cuff result ed in an average 100.2 % compliance rate with mean decreases of 15 mm Hg ( P = .0006 ) and 6.60 mm Hg ( P = .0006 ) in systolic and diastolic pressures , respectively . Results of the two-phase study showed statistically significant increases in medication compliance associated with statistically and clinical ly significant reductions in blood pressure for all patients using the timepiece cap STUDY OBJECTIVES To evaluate whether direct feedback discussion on inhaled steroid use might influence subsequent adherence with this therapy . DESIGN AND SETTING A 10-week , single-blind , r and omized trial in asthma patients . Inclusion criteria included forced expiratory volume in 1 second < 80 % , one or more markers for low socioeconomic status , and the use of inhaled steroids . Inhaled steroid and beta-agonist use were electronically monitored . All patients received st and ard asthma care . The treatment group received direct clinician-to-patient feedback discussion on their inhaled steroid and beta-agonist use on all subsequent visits , whereas this information was withheld during the study period in the control group . MEASURES 1 ) Mean weekly inhaled steroid adherence [ ( number of actuations/prescribed number of actuations ) x 100 ] ; 2 ) number of days with overuse of inhaled steroids ; 3 ) 24-hour and nighttime albuterol use ; 4 ) included forced expiratory volume in 1 second ; and 5 ) Asthma Quality of Life Question naire total score . RESULTS Ten treatment and nine control patients completed the study . Mean weekly inhaled steroid adherence over the first week was not significantly different in the treatment and control groups : 61 + /- 9 % versus 51 + /- 5 % , respectively . However , by the second week , adherence increased to 81 + /- 7 % in the treatment group , whereas it decreased to 47 + /- 7 % in the control group ( P = 0.003 ) . Adherence remained above 70 % in the treatment group for the entire trial , but continued to decrease in the control group . Overuse of inhaled steroids was low in both groups . There were no group differences in any of the asthma outcomes . CONCLUSIONS Direct clinician-to-patient feedback discussion on inhaled steroid use using electronic printouts did improve adherence in the short-term in asthma patients at high-risk for poor adherence BACKGROUND Adherence to medication regimens is poor in the management of chronic diseases , including asthma . OBJECTIVE To determine whether an audiovisual reminder device improves adherence with inhaled corticosteroid ( ICS ) therapy in adult asthma . METHODS A r and omized open-label parallel group study of 110 adult or adolescent subjects with asthma was undertaken . Subjects were r and omized to receive 24 weeks of fluticasone propionate 250 microg , 1 actuation twice daily via a metered dose inhaler ( MDI ) with or without an audiovisual reminder function ( AVRF ) . All MDIs had electronic covert adherence monitors . The primary outcome variable was adherence , defined as the proportion of medication taken as prescribed over the final 12 weeks of the study . Adherence was also assessed as the proportion of subjects who took > 50 % , > 80 % , or > 90 % of prescribed medication . RESULTS The proportion of medication taken in the last 12 weeks was greater in the AVRF group ( 93 % ) compared with the control group ( 74 % ) , with a difference of 18 % ( 95 % confidence interval [ CI ] 10 - 26 % ; P < .0001 ) . The proportion of subjects taking > 50 % , > 80 % , or > 90 % of their medication was greater in the AVRF group , with a ratio of proportions adherent of 1.33 ( 95 % CI , 1.10 - 1.61 ; P = .003 ) , 2.27 ( 95 % CI , 1.56 - 3.3 ; P < .0001 ) , and 3.25 ( 95 % CI , 1.74 - 6.1 % ; P < .0001 ) , respectively . CONCLUSION An audiovisual reminder function can significantly improve adherence with ICS therapy in adult asthma . CLINICAL IMPLICATION S An audiovisual reminder function has potential to improve adherence with medication regimens across a wide spectrum of diseases , in both research and clinical practice BACKGROUND This study was performed to investigate the use of an electronic medication alarm device ( Prescript TimeCap ) to enhance compliance in glaucoma patients taking pilocarpine . METHODS Thirteen subjects were selected who had been diagnosed with open-angle glaucoma and were receiving 1 drop of pilocarpine solution 4 times a day in both eyes . For each subject , the study was divided into 2 30-day phases , one with the medication alarm device and the other without . Thus , each subject served as his or her own control . Compliance was measured based on the amount of pilocarpine used and by patient question naire . In addition , the subjects completed a post- study question naire regarding the ease of use of the TimeCap and whether it helped them remember to take their medication . RESULTS When subjects used the TimeCap , they administered an average of 2.867 g ( P < 0.0001 ) more pilocarpine over the 30 days than during the period without it . Subjects also estimated a significant difference in compliance level , 95.8 percent with the alarm device versus 83.1 percent without it ( p < 0.01 ) . All subjects reported no difficulty using the TimeCap , and all reported that it helped them remember to take their medication . CONCLUSIONS These results are highly suggestive that the TimeCap is an effective compliance aid for glaucoma patients on pilocarpine Context Patients sometimes have difficulty following complicated treatment regimens . Contribution In this trial , 314 low-income patients with congestive heart failure were r and omly assigned to a pharmacist intervention or usual care . The pharmacist assessed patient knowledge and provided instructions about medication use . During the 9-month intervention , patients in the intervention group had greater medication adherence than patients in the usual care group ( 79 % vs. 68 % ) . These differences dissipated within 3 months of stopping the intervention . Patients in the intervention group also had fewer exacerbations result ing in emergency department visits or hospitalizations than patients in the usual care group . Implication Ongoing educational intervention by a pharmacist can improve medication adherence and outcomes in patients with heart failure . The Editors In the United States , 5 million people have heart failure , with total health care costs exceeding $ 29 billion ( 1 ) . These costs are largely derived from expensive exacerbations that require emergency visits and hospitalizations ( 1 , 2 ) . Regularly administered cardiovascular medications may preserve cardiac function , improve quality of life , and reduce risk for costly exacerbations . However , patients sometimes do not adhere to prescribed instructions and have poor outcomes ( 35 ) . Research ers have estimated that approximately 50 % of patients with chronic illnesses do not take their medications as prescribed ( 6 ) . Reasons for nonadherence include lack of patient knowledge , skills , and support to appropriately self-manage complicated medication regimens ( 7 , 8) . Although chronic disease management programs abound , few studies have rigorously tested interventions aim ed at improving patient adherence to prescribed medications and their effect on health outcomes ( 9 , 10 ) . We conducted a r and omized clinical trial to assess the effect of a pharmacist intervention on patients who are socioeconomically disadvantaged and medically vulnerable . We hypothesized that the intervention would improve adherence to heart failure medications , reduce exacerbations requiring emergency department visits or hospitalization , improve disease-specific quality of life , increase patient satisfaction , and reduce health care costs . Methods Design Overview The methods for our r and omized trial are described elsewhere ( 1113 ) . We recruited patients from the general medicine and cardiology practice s of Wishard Health Services , Indianapolis , Indiana , which serves socioeconomically disadvantaged and medically vulnerable patients . The study was conducted from February 2001 to June 2004 . Patients took part in the study for 12 months and received 9 months of active intervention by the pharmacist or usual care followed by 3 months of postintervention assessment . Patients in the usual care and intervention groups visited the same pharmacy location , but the intervention pharmacist was instructed to have no contact with patients in the usual care group . The institutional review boards of Indiana UniversityPurdue University and the University of North Carolina at Chapel Hill approved this study . Setting and Patients Indiana University Medical Group , Indianapolis , is an academic primary care group practice composed of primary and specialty care clinics affiliated with Wishard Health Services . Faculty physicians , residents , and nurse practitioners provide care to 13000 adults ( mean age , 57 years [ SD , 15 ] ; 60 % women ; 50 % African American ) . Annually , these patients make approximately 50000 visits to practice s , 72000 visits to emergency departments , and 135000 visits to pharmacies and have 16000 hospitalizations . We recruited patients from 4 identical general medicine practice s , 1 cardiology practice , and Wishard Memorial Hospital . Practice s met in half-day sessions per week that were attended by 2 or 3 faculty members and 3 to 5 residents or fellows from each practice . Faculty physicians practice d 1 to 5 half-days per week , whereas fellows practice d 1 to 2 half-days per week and residents attended the practice 1 half-day per week . Out patients of Wishard Health Services fill their prescriptions at central or de central ized outpatient pharmacies located at the ambulatory care center or at 1 of several satellite pharmacies stationed at neighborhood clinics . Fully stocked de central ized pharmacies serviced all study patients . From February 2001 to January 2003 , the study pharmacy was located in a building adjacent to the ambulatory care center . From February 2003 to June 2004 , the study pharmacy was moved to a space adjacent to the general medicine practice s in the ambulatory care center . Two pharmacists and 1 technician were stationed at the pharmacy . The study pharmacist was instructed to service patients in the intervention group only , and a second pharmacist serviced patients in the usual care group and filled prescriptions to be delivered to patients at outlying clinics . The technician filled prescriptions and read electronic adherence monitors . Weekly lists of eligible patients were created by using the Regenstrief Medical Record System ( Regenstrief Institute , Indianapolis , Indiana ) ( 14 , 15 ) . We invited clinical ly stable patients from general internal medicine practice s , a cardiology clinic , and Wishard Memorial Hospital ( at discharge ) to participate in the study . Of 3034 patients with a diagnosis of heart failure , 1512 met criteria for enrollment . Patients were eligible if they were 50 years of age or older ; planned to receive all of their care , including prescribed medications , at Wishard Health Services ; had a diagnosis of heart failure confirmed by their primary care physician ; regularly used at least 1 cardiovascular medication for heart failure ( angiotensin-converting enzyme [ ACE ] inhibitor or angiotensin-receptor blocker , -adrenergic antagonist , diuretic , digoxin , or aldosterone antagonist ) ; were not using or were not planning to use a medication container adherence aid ( for example , a pill box ) ; had access to a working telephone ; and could hear within the range of normal conversation . We excluded patients with dementia . Patients received their prescription medications through state and local assistance plans at no cost . Thus , cost of medicines was not a deterrent to adherence . R and omization A trained interviewer conducted a baseline interview at enrollment . Interviewers were blinded to patients ' study status and played no role in the delivery of the intervention . Interviewers contacted a central ized data manager at the end of each interview to determine the patient 's study assignment , which was otherwise concealed . We r and omly assigned patients , without blocking or stratification , to receive the pharmacy intervention or usual care by using a univariate discrete distribution from the IMSL Fortran Library 's subroutine RNGDA pseudor and om number generator ( Absoft Corp. , Rochester Hills , Michigan ) ( 16 ) . We r and omly assigned more patients to the usual care group so that this group could also be a prospect i ve cohort for study ing risk factors associated with the clinical deterioration of heart failure . Of the 314 patients included in the study , 229 were recruited from the general internal medicine practice s , 15 from the cardiology clinic , and 70 on discharge from the Wishard Memorial Hospital . The numbers of patients assigned to the intervention and usual care groups did not differ by recruitment site ( P= 0.83 ) . Intervention A pharmacist delivered the intervention by using a protocol ( Appendix Table 1 ) that included a baseline medication history of all prescription and over-the-counter drugs and dietary supplements taken by patients , which patients brought with them to the baseline interview , and the results of an assessment of patient medication knowledge and skills ( 7 , 8) . The pharmacist dispensed enough of the patient 's medications to last approximately 2 months . Appendix Table 1 . Pharmacist 's Intervention Protocol * When medications were dispensed , the pharmacist provided patient-centered verbal instructions and written material s about the medications ( 11 , 13 , 17 ) by using a schema for instruction that has been tested ( 18 , 19 ) . We assigned each medication category an icon ( for example , the icon for ACE inhibitors was a red ace of hearts ) . The same icon appeared on the container label and lid and on the written patient instructions . Written instructions were aim ed at patients with low health literacy and contained an easy-to-follow timeline to remind patients when to take their medications ( 13 ) . The pharmacist monitored patients ' medication use , health care encounters , body weight , and other relevant data by using a study data base ( 20 , 21 ) . Information about patients was communicated as needed to clinic nurses and primary care physicians by face-to-face visits , telephone , paging ( physician only ) , and e-mail ( physician only ) . Technicians supported the pharmacist 's dispensing efforts within the pharmacy throughout the study . We incorporated costs therein into the economic analysis . Pharmacists serviced patients in the usual care group who were not associated with the intervention or the study . An interdisciplinary team of investigators that included pharmacists with advanced training in patient education and cardiovascular pharmacotherapy , a geriatrician , a cardiologist with expertise in heart failure , a behavioral scientist , and a cognitive psychologist trained the intervention pharmacist . The intervention pharmacist also studied guidelines for treating heart failure ( 22 ) , key concepts in the pharmaceutical care of older adults , communication techniques , and the pharmacotherapy of the cardiovascular drugs for heart failure . All pharmacists at Wishard Health Services were aware of the study and were instructed on how to h and le and redirect intervention patients who inadvertently arrived at their pharmacy . Usual Care Patients in the usual care group were aware of the purpose of the study , and their primary care The Lung Health Study is a 10-center 5-year clinical trial sponsored by the National Heart , Lung , and Blood Institute to evaluate the effectiveness of early intervention in chronic obstructive pulmonary disease ( COPD ) . The specific objectives of the trial are to determine whether the accelerated decline in lung function characteristic of COPD and morbidity due to COPD can be reduced by special intervention at a relatively early stage in the evolution of the disease . Special intervention consists of a smoking-cessation program and the use of an inhaled bronchodilator to suppress airway hyperreactivity . The use of the inhaler canister is monitored every 4 months by canister weighing and , at two of the 10 centers , by an electronic recording device , the Nebulizer Chronolog . Among trial participants assigned the latter device , results from the first 4 months of the study indicate that only 52 % of trial participants who were uninformed as to the nature of the chronolog used their inhaler at least twice daily as measured by the chronolog , compared with 87 % as determined by self-report . Satisfactory or good compliance was achieved by 52 % of these subjects as measured by the chronolog compared with 85 % as assessed by canister weighing . Eighteen percent of uninformed participants " dumped " their inhalers within a 3-hour time period , contributing to the inaccuracy of canister weights as an indicator of compliance . Feedback of information to the participants from the chronolog improved the level of compliance and eliminated the " dumping " phenomenon . We conclude that , when accurate determinations of compliance are important , as in a drug trial , objective medication monitors should be considered . Electronic monitoring of inhaler use can provide valuable feedback , which encourages improved compliance OBJECTIVE To investigated the effectiveness of an adherence intervention ( AIMS ) design ed to fit HIV-clinics ' routine care procedures . DESIGN Through block r and omization , patients were allocated to the intervention or control group . The study included 2 months baseline measurement , 3 months intervention , and 4 months follow-up . HIV-nurses delivered a minimal intervention ( " adherence sustaining " ) to patients scoring > 95 % adherence at baseline , and an intensive intervention ( " adherence improving " ) to patients with < 95 % adherence . Control participants received high- quality usual care . MAIN OUTCOME MEASURES Electronically monitored adherence and viral load . RESULTS 133 patients were included ( 67 control , 66 intervention ) , 60 % had < 95 % adherence at baseline , and 87 % ( 116/133 ) completed the trial . Intent-to-treat analyses showed that adherence improved significantly in the complete intervention sample . Subgroup analyses showed that this effect was caused by participants scoring < 95 % at baseline ( mean difference = 15.20 % ; p < .001 ) . These effects remained stable during follow-up . The number of patients with an undetectable viral load increased in the intervention group compared to the control group ( OR = 2.96 , p < .05 ) . Treatments effects on viral load were mediated by the improvements in adherence . CONCLUSIONS The AIMS -intervention was effective and can be integrated in routine clinical care for HIV-infected patients . Future research should study its (cost)effectiveness among more heterogeneous sample s and in setting s with variable levels of st and ard care Background High blood pressure ( BP ) significantly increases overall cardiovascular risk , the incidence of ischemic heart disease and stroke . One of the most important causes of insufficient BP control is low treatment compliance . Reminders and electronic compliance monitoring have been shown to be effective in improving patient compliance to some extent , but the combined effect has not been documented . Objective To assess the impact of an electronic reminder and monitoring device on patient compliance and BP control . Methods All patients received medical treatment with telmisartan once daily and were r and omized to either electronic compliance monitoring with a reminder and monitoring device or st and ard therapy for 6 months . Both groups were crossed over after 6 months . Intervention effectiveness was assessed using self-reported compliance and BP . Results Data from 398 patients were analysed . In the first half of the study , patients using the device reported 91 % compliance versus 85 % in the control group . This difference diminished after crossover ( 88 versus 86 % ) . BP was not affected . Electronic monitoring data on compliance revealed taking , dosing and timing compliance between 45 and 52 % in study group 1 , and between 32 and 38 % in study group 2 . Conclusion The Helping H and reminder device was most suitable if used for newly diagnosed hypertensive patients , when it improved compliance by 6 % . With the present medical treatment , the device does not have any influence on BP control , but with less forgiving medications , the device might make a significant difference . The use of the device can be an easy and effective way to improve compliance in selected patients |
2,137 | 25,863,305 | Bivariate analysis revealed that CCTA had statistically greater sensitivity , specificity , PPV and overall diagnostic accuracy when compared to SE and SPECT .
CONCLUSIONS All three modalities , when employed by an experienced clinician , are highly accurate .
Each has its own strengths and limitations making each well suited for different patient groups .
CCTA has higher accuracy than SE and SPECT , but it has many drawbacks , most importantly its lack of physiologic data | BACKGROUND The aim of this meta- analysis was to compare the diagnostic accuracy of cardiac computed tomographic angiography ( CCTA ) , stress echocardiography ( SE ) and radionuclide single photon emission computed tomography ( SPECT ) for the assessment of chest pain in emergency department ( ED ) setting . | OBJECTIVES The aim of this study was to determine the diagnostic performance of a new method for quantifying fractional flow reserve ( FFR ) with computational fluid dynamics ( CFD ) applied to coronary computed tomography angiography ( CCTA ) data in patients with suspected or known coronary artery disease ( CAD ) . BACKGROUND Measurement of FFR during invasive coronary angiography is the gold st and ard for identifying coronary artery lesions that cause ischemia and improves clinical decision-making for revascularization . Computation of FFR from CCTA data ( FFR(CT ) ) provides a noninvasive method for identifying ischemia-causing stenosis ; however , the diagnostic performance of this new method is unknown . METHODS Computation of FFR from CCTA data was performed on 159 vessels in 103 patients undergoing CCTA , invasive coronary angiography , and FFR . Independent core laboratories determined FFR(CT ) and CAD stenosis severity by CCTA . Ischemia was defined by an FFR(CT ) and FFR ≤0.80 , and anatomically obstructive CAD was defined as a CCTA with stenosis ≥50 % . Diagnostic performance of FFR(CT ) and CCTA stenosis was assessed with invasive FFR as the reference st and ard . RESULTS Fifty-six percent of patients had ≥1 vessel with FFR ≤0.80 . On a per-vessel basis , the accuracy , sensitivity , specificity , positive predictive value , and negative predictive value were 84.3 % , 87.9 % , 82.2 % , 73.9 % , 92.2 % , respectively , for FFR(CT ) and were 58.5 % , 91.4 % , 39.6 % , 46.5 % , 88.9 % , respectively , for CCTA stenosis . The area under the receiver-operator characteristics curve was 0.90 for FFR(CT ) and 0.75 for CCTA ( p = 0.001 ) . The FFR(CT ) and FFR were well correlated ( r = 0.717 , p < 0.001 ) with a slight underestimation by FFR(CT ) ( 0.022 ± 0.116 , p = 0.016 ) . CONCLUSIONS Noninvasive FFR derived from CCTA is a novel method with high diagnostic performance for the detection and exclusion of coronary lesions that cause ischemia STUDY OBJECTIVE Coronary computed tomographic ( CT ) angiography has excellent performance characteristics relative to coronary angiography and exercise or pharmacologic stress testing . We hypothesize that coronary CT angiography can identify a cohort of emergency department ( ED ) patients with a potential acute coronary syndrome who can be safely discharged with a less than 1 % risk of 30-day cardiovascular death or nonfatal myocardial infa rct ion . METHODS We conducted a prospect i ve cohort study at an urban university hospital ED that enrolled consecutive patients with potential acute coronary syndromes and a low TIMI risk score who presented to the ED with symptoms suggestive of a potential acute coronary syndrome and received a coronary CT angiography . Our intervention was either immediate coronary CT angiography in the ED or after a 9- to 12-hour observation period that included cardiac marker determinations , depending on time of day . The main clinical outcome was 30-day cardiovascular death or nonfatal myocardial infa rct ion . RESULTS Five hundred sixty-eight patients with potential acute coronary syndrome were evaluated : 285 of these received coronary CT angiography immediately in the ED and 283 received coronary CT angiography after a brief observation period . Four hundred seventy-six ( 84 % ) were discharged home after coronary CT angiography . During the 30-day follow-up period , no patients died of a cardiovascular event ( 0 % ; 95 % confidence interval [ CI ] 0 % to 0.8 % ) or sustained a nonfatal myocardial infa rct ion ( 0 % ; 95 % CI 0 to 0.8 % ) . CONCLUSION ED patients with symptoms concerning for a potential acute coronary syndrome with a low TIMI risk score and a nonischemic initial ECG result can be safely discharged home after a negative coronary CT angiography test result BACKGROUND Multidetector computed tomography ( MDCT ) has high diagnostic value for detecting or excluding coronary artery stenosis . We examined performance characteristics of MDCT for diagnosing or excluding an acute coronary syndrome in patients presenting to the emergency department ( ED ) with possible ischemic chest pain and examined relation to clinical outcome during a 15-month follow-up period . METHODS AND RESULTS We prospect ively studied 58 patients ( 56+/-10 years of age , 36 % female ) with chest pain possibly ischemic in origin and no new ECG changes or elevated biomarkers . The patients underwent 64-slice contrast-enhanced MDCT , which showed normal coronary vessels ( no or trivial atheroma ) in 15 patients , nonobstructive plaque in 20 ( MDCT-negative patients ) , and obstructive coronary disease ( > or = 50 % luminal narrowing ) in 23 ( MDCT-positive group ) . By further investigation ( new elevation of cardiac biomarkers , abnormal myocardial perfusion scintigraphy and /or invasive angiography ) , acute coronary syndrome was diagnosed in 20 of the 23 MDCT-positive patients ( ED MDCT sensitivity 100 % [ 20/20 ] , specificity 92 % [ 35/38 ] , positive predictive value 87 % [ 20/23 ] , negative predictive value 100 % [ 35/35 ] ) . During a 15-month follow-up period , no deaths or myocardial infa rct ions occurred in the 35 patients discharged from the ED after initial triage and MDCT findings . One patient underwent late percutaneous coronary intervention ( late major adverse cardiovascular events rate , 2.8 % ) . Overall , ED MDCT sensitivity for predicting major adverse cardiovascular events ( death , myocardial infa rct ion , or revascularization ) during hospitalization and follow-up was 92 % ( 12/13 ) , specificity was 76 % ( 34/45 ) , positive predictive value was 52 % ( 12/23 ) , and negative predictive value was 97 % ( 34/35 ) . CONCLUSIONS We found that 64-slice cardiac MDCT is a potentially valuable diagnostic tool in ED patients with chest pain of uncertain origin , providing early direct noninvasive visualization of coronary anatomy . ED MDCT had high positive predictive value for diagnosing acute coronary syndrome , whereas a negative MDCT study predicted a low rate of major adverse cardiovascular events and favorable outcome during follow-up With the advent of multislice CT more than a decade ago , multislice CT angiography has demonstrated a huge potential in the less invasive imaging of cardiovascular disease , especially in the diagnosis of coronary artery disease . The diagnostic accuracy of multislice CT angiography has been significantly augmented with the rapid technical developments ranging from the initial 4-slice , to the current 64-slice and 256 and 320-slice CT scanners . This is mainly demonstrated by the improved spatial and temporal resolution when compared to the earlier type of CT scanners . Traditionally , multislice CT angiography is acquired with retrospective ECG-gating with acquisition of volume data at the expense of increased radiation dose , since data is acquired at the entire cardiac cycle , although not all of them are used for postprocessing or reconstructions . Recently , there is an increasing trend of utilising prospect i ve ECG-gating in cardiac imaging with latest multislice CT scanners ( 64 or more slices ) with significant reduction of radiation dose when compared to retrospective ECG-gating method . However , there is some debate as to the diagnostic value of prospect i ve ECG-gating in the diagnosis of coronary artery disease , despite its attractive ability to reduce radiation dose . This article will review the performance of retrospective ECG-gating in the diagnostic value of coronary artery disease , highlight the potential applications of prospect i ve ECG-gating , and explore the future directions of multislice CT angiography in cardiac imaging OBJECTIVES The goal of this study was to determine the diagnostic performance of noninvasive fractional flow reserve ( FFR ) derived from st and ard acquired coronary computed tomography angiography ( CTA ) data sets ( FFR(CT ) ) for the diagnosis of myocardial ischemia in patients with suspected stable coronary artery disease ( CAD ) . BACKGROUND FFR measured during invasive coronary angiography ( ICA ) is the gold st and ard for lesion-specific coronary revascularization decisions in patients with stable CAD . The potential for FFR(CT ) to noninvasively identify ischemia in patients with suspected CAD has not been sufficiently investigated . METHODS This prospect i ve multicenter trial included 254 patients scheduled to undergo clinical ly indicated ICA for suspected CAD . Coronary CTA was performed before ICA . Evaluation of stenosis ( > 50 % lumen reduction ) in coronary CTA was performed by local investigators and in ICA by an independent core laboratory . FFR(CT ) was calculated and interpreted in a blinded fashion by an independent core laboratory . Results were compared with invasively measured FFR , with ischemia defined as FFR(CT ) or FFR ≤0.80 . RESULTS The area under the receiver-operating characteristic curve for FFR(CT ) was 0.90 ( 95 % confidence interval [ CI ] : 0.87 to 0.94 ) versus 0.81 ( 95 % CI : 0.76 to 0.87 ) for coronary CTA ( p = 0.0008 ) . Per-patient sensitivity and specificity ( 95 % CI ) to identify myocardial ischemia were 86 % ( 95 % CI : 77 % to 92 % ) and 79 % ( 95 % CI : 72 % to 84 % ) for FFR(CT ) versus 94 % ( 86 to 97 ) and 34 % ( 95 % CI : 27 % to 41 % ) for coronary CTA , and 64 % ( 95 % CI : 53 % to 74 % ) and 83 % ( 95 % CI : 77 % to 88 % ) for ICA , respectively . In patients ( n = 235 ) with intermediate stenosis ( 95 % CI : 30 % to 70 % ) , the diagnostic accuracy of FFR(CT ) remained high . CONCLUSIONS FFR(CT ) provides high diagnostic accuracy and discrimination for the diagnosis of hemodynamically significant CAD with invasive FFR as the reference st and ard . When compared with anatomic testing by using coronary CTA , FFR(CT ) led to a marked increase in specificity . ( HeartFlowNXT-HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography [ HFNXT ] ; NCT01757678 ) OBJECTIVES We prospect ively studied the prognostic value of predischarge dobutamine stress echocardiography ( DSE ) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram ( ECG ) and a negative serial troponin T. BACKGROUND Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain . The prognostic value of immediate DSE has not been studied in a blinded , prospect i ve fashion . METHODS Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible . Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a st and ard rule-out protocol and a negative serial troponin T ; the occurrence of any new wall motion abnormality was considered positive . Results were kept blinded . End points were cardiac death , myocardial infa rct ion , rehospitalization for unstable angina or revascularization . RESULTS In total , 377 patients were included . There were 2 deaths , 2 myocardial infa rct ions , 8 rehospitalization for unstable angina , and 10 revascularizations at six-month follow-up . The end points occurred in 8/26 ( 30.8 % ) patients with a positive versus 14/351 ( 4.0 % ) patients with a negative DSE ( odds ratio , 10.7 ; 95 % confidence interval , 4.0 to 28.8 ; p < 0.0001 ) . By multivariate analysis , DSE remained a predictor of end points ( p < 0.0001 ) . CONCLUSIONS A predischarge DSE had important , independent prognostic value in low-risk , troponin negative , chest pain patients Objectives To assess feasibility , image quality , and radiation dose of prospect ively ECG-triggered coronary CT angiography ( CTA ) in orthotopic heart transplant ( OHT ) recipients . Methods 47 consecutive OHT recipients ( 40 men , mean age 62.1±10.9 years , mean heart rate 86.3±14.4 bpm ) underwent dual- source CTA to rule out coronary allograft vasculopathy in a prospect ively ECG-triggered mode with data acquisition during 35 % to 45 % of the cardiac cycle . Two independent observers blindly assessed image quality on a per-segment and per-vessel basis using a four-point scale ( 1-excellent , 4-not evaluable ) . Scores 1–3 were considered acceptable for diagnosis . Multivariate analysis was performed to evaluate differences between image quality scores obtained at different reconstruction intervals . Effective radiation doses were calculated . Results 671 coronary segments were evaluated . Interobserver agreement on the image quality was κ=0.75 . Diagnostic image quality was observed in 93.9 % , 95.5 % and 93.3 % of the segments at 35 % , 40 % and 45 % reconstruction intervals . Mean image quality score was 1.5±0.7 for the entire coronary tree , 1.4±0.7 for the RCA , 1.6±0.8 for the LCA and 1.6±0.7 for the Cx at the best reconstruction interval . Estimated mean radiation dose was 4.5±1.2 mSv . ConclusionS ystolic prospect ively ECG-triggered CTA allows diagnostic image quality coronary angiograms in OHT recipients at low radiation doses OBJECTIVES This study sought to compare the safety , diagnostic efficacy , and efficiency of multi-slice computed tomography ( MSCT ) with st and ard diagnostic evaluation of low-risk acute chest pain patients . BACKGROUND Over 1 million patients have emergency center evaluations for acute chest pain annually , at an estimated diagnostic cost of over $ 10 billion . Multi-slice computed tomography has a high negative predictive value for exclusion of coronary artery stenoses . METHODS We r and omized patients to MSCT ( n = 99 ) versus SOC ( n = 98 ) protocol s. The MSCT patients with minimal disease were discharged ; those with stenosis > 70 % underwent catheterization , whereas cases with intermediate lesions or non-diagnostic scans underwent stress testing . Outcomes included : safety ( freedom from major adverse events over 6 months ) , diagnostic efficacy ( clinical ly correct and definitive diagnosis ) , as well as time and cost of care . RESULTS Both approaches were completely ( 100 % ) safe . The MSCT alone immediately excluded or identified coronary disease as the source of chest pain in 75 % of patients , including 67 with normal coronary arteries and 8 with severe disease referred for invasive evaluation . The remaining 25 % of patients required stress testing , owing to intermediate severity lesions or non-diagnostic scans . During the index visit , MSCT evaluation reduced diagnostic time compared with SOC ( 3.4 h vs. 15.0 h , p < 0.001 ) and lowered costs ( 1,586 dollars vs. 1,872 dollars , p < 0.001 ) . Importantly , MSCT patients required fewer repeat evaluations for recurrent chest pain ( MSCT , 2 of 99 ( 2.0 % ) patients vs. SOC , 7 of 99 ( 7 % ) patients ; p = 0.10 ) . CONCLUSIONS Multi-slice computed tomographic coronary angiography can definitively establish or exclude coronary disease as the cause of chest pain . However , inability to determine the physiological significance of intermediate severity coronary lesions and cases with inadequate image quality are present limitations . ( Study of Coronary Artery Computed Tomography to Diagnose Emergency Chest Pain CR ; http:// clinical trials.gov/ct/show/NCT00273832?order=1 ; NCT00273832 ) BACKGROUND It is unclear whether an evaluation incorporating coronary computed tomographic angiography ( CCTA ) is more effective than st and ard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes . METHODS In this multicenter trial , we r and omly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to st and ard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012 . The primary end point was length of stay in the hospital . Secondary end points included rates of discharge from the emergency department , major adverse cardiovascular events at 28 days , and cumulative costs . Safety end points were undetected acute coronary syndromes . RESULTS The rate of acute coronary syndromes among 1000 patients with a mean ( ±SD ) age of 54±8 years ( 47 % women ) was 8 % . After early CCTA , as compared with st and ard evaluation , the mean length of stay in the hospital was reduced by 7.6 hours ( P<0.001 ) and more patients were discharged directly from the emergency department ( 47 % vs. 12 % , P<0.001 ) . There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days . After CCTA , there was more downstream testing and higher radiation exposure . The cumulative mean cost of care was similar in the CCTA group and the st and ard-evaluation group ( $ 4,289 and $ 4,060 , respectively ; P=0.65 ) . CONCLUSIONS In patients in the emergency department with symptoms suggestive of acute coronary syndromes , incorporating CCTA into a triage strategy improved the efficiency of clinical decision making , as compared with a st and ard evaluation in the emergency department , but it result ed in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care . ( Funded by the National Heart , Lung , and Blood Institute ; ROMICAT-II Clinical Trials.gov number , NCT01084239 . ) BACKGROUND Emergency room ( ER ) evaluation of patients with acute chest pain and non-diagnostic electrocardiography ( ECG ) remains a frequent and difficult problem . AIM To assess safety and prognostic implication s of pharmacological stress echocardiography in the ER chest pain unit ( CPU ) . METHODS A total of 552 patients ( 321 males , age 58+/-12.6 years ) with acute chest pain , negative serial enzymes and /or troponin , and ECG recordings , and normal/unchanged resting left ventricular function were prospect ively enrolled and underwent pharmacological ( dipyridamole or dobutamine ) stress echo . Six echo labs that had passed the preliminary quality control for stress echo reading entered the study . Follow-up was obtained in all patients after a median period of 13 months . RESULTS No significant adverse events were observed during the test . Stress echocardiography was negative in 502 patients ( 91 % ) and positive in 50 ( 9 % ) . The 502 patients with negative stress echocardiography were discharged with no or unchanged anti-ischemic medications . While the 50 patients with positive stress echo were admitted to the coronary care unit , 44 of these underwent coronary angiography with the result that 42 out of 44 showed significant coronary artery disease . There were 45 events in the follow-up : six in the 502 patients with negative and 39 in the 50 patients with positive stress echo ( 1.2 % vs. 78 % , p<0.001 ) . The negative predictive value of stress echocardiography was 98.8 % for all events and 99.6 % for hard events . CONCLUSIONS Stress echocardiography is a feasible , safe , and effective tool for early stratification of patients admitted to the ER with acute chest pain and non-ischemic ECG and resting echo STUDY OBJECTIVE We compared the accuracy of multidetector computed tomography ( CT ) coronary angiography with stress nuclear imaging for the detection of an acute coronary syndrome or 30-day major adverse cardiac events in low-risk chest pain patients . METHODS This was a prospect i ve study of the diagnostic accuracy of myocardial perfusion imaging and multidetector CT in low-risk chest pain patients . The target condition was an acute coronary syndrome ( confirmed > 70 % coronary stenosis on coronary artery catheterization ) or major adverse cardiac events within 30 days . Patients were low risk by Reilly/Goldman criteria and had negative serial ECGs and cardiac markers . All had both rest/stress sestamibi nuclear imaging and multidetector CT . Patients with abnormal stress nuclear imaging results ( reversible perfusion defects ) or multidetector CT results ( stenosis > 50 % or calcium score > 400 ) were considered for cardiac catheterization , and those with discordant results had a greater than 30-day reevaluation ( including ECG ) by a cardiologist . All were followed up for evidence of major adverse cardiac events within 30 days by review of hospital records and structured telephone interview . Primary outcomes were the accuracy of multidetector CT and myocardial perfusion imaging for the detection of an acute coronary syndrome and 30-day major adverse cardiac events . RESULTS Of the 92 patients , 7 ( 8 % ) were excluded because of uninterpretable multidetector CT scans . Of the remaining 85 study patients ( 49+/-11 years , 53 % men ) , 7 ( 8 % ) were found to have the target condition , with all having significant coronary stenosis ( 88%+/-9 % ) and none having myocardial infa rct ion or major adverse cardiac events during 30 days . Stress nuclear imaging results were negative in 72 ( 85 % ) patients , and multidetector CT results were negative in 73 ( 86 % ) patients . The sensitivity of stress nuclear imaging was 71 % ( 95 % confidence interval [ CI ] 36 % to 92 % ) , and multidetector CT was 86 % ( 95 % CI 49 % to 97 % ) , and the specificity was 90 % ( 95 % CI 81 % to 95 % ) and 92 % ( 95 % CI 84 % to 96 % ) , respectively . The negative predictive value of stress nuclear imaging and multidetector CT was 97 % ( 95 % CI 90 % to 99 % ) and 99 % ( 95 % CI 93 % to 100 % ) , respectively , and the positive predictive value was 38 % ( 95 % CI 18 % to 64 % ) and 50 % ( 95 % CI 25 % to 75 % ) , respectively . CONCLUSION The accuracy of multidetector CT is at least as good as that of stress nuclear imaging for the detection and exclusion of an acute coronary syndrome in low-risk chest pain patients BACKGROUND Admission rates among patients presenting to emergency departments with possible acute coronary syndromes are high , although for most of these patients , the symptoms are ultimately found not to have a cardiac cause . Coronary computed tomographic angiography ( CCTA ) has a very high negative predictive value for the detection of coronary disease , but its usefulness in determining whether discharge of patients from the emergency department is safe is not well established . METHODS We r and omly assigned low-to-intermediate-risk patients presenting with possible acute coronary syndromes , in a 2:1 ratio , to undergo CCTA or to receive traditional care . Patients were enrolled at five centers in the United States . Patients older than 30 years of age with a Thrombolysis in Myocardial Infa rct ion risk score of 0 to 2 and signs or symptoms warranting admission or testing were eligible . The primary outcome was safety , assessed in the subgroup of patients with a negative CCTA examination , with safety defined as the absence of myocardial infa rct ion and cardiac death during the first 30 days after presentation . RESULTS We enrolled 1370 subjects : 908 in the CCTA group and 462 in the group receiving traditional care . The baseline characteristics were similar in the two groups . Of 640 patients with a negative CCTA examination , none died or had a myocardial infa rct ion within 30 days ( 0 % ; 95 % confidence interval [ CI ] , 0 to 0.57 ) . As compared with patients receiving traditional care , patients in the CCTA group had a higher rate of discharge from the emergency department ( 49.6 % vs. 22.7 % ; difference , 26.8 percentage points ; 95 % CI , 21.4 to 32.2 ) , a shorter length of stay ( median , 18.0 hours vs. 24.8 hours ; P<0.001 ) , and a higher rate of detection of coronary disease ( 9.0 % vs. 3.5 % ; difference , 5.6 percentage points ; 95 % CI , 0 to 11.2 ) . There was one serious adverse event in each group . CONCLUSIONS A CCTA-based strategy for low-to-intermediate-risk patients presenting with a possible acute coronary syndrome appears to allow the safe , expedited discharge from the emergency department of many patients who would otherwise be admitted . ( Funded by the Commonwealth of Pennsylvania Department of Health and the American College of Radiology Imaging Network Foundation ; Clinical Trials.gov number , NCT00933400 . ) Background / Aims : Early evaluations of patients presenting with acute chest pain remain difficult . We examined the diagnostic capacity of multidetector computed tomography ( MDCT ) for acute coronary syndrome ( ACS ) in patients presenting with acute chest pain . Methods / Results : We examined 36 consecutive patients presenting with acute chest pain with neither diagnostic ECG changes nor elevated biomarkers . 64-slice MDCT was performed , and we evaluated the presenceof significant coronaryartery stenosis ( > 50 % reduction in lumen diameter ) . Significant stenosis was detected in 15 patients by MDCT . Among them , 11 patients were diagnosed as having ACS based on the findings of coronary angiography or myocardial perfusion single photon emission computed tomography ( positive predictive value 73 % ) . All 21 patients without significant stenosis by MDCT , except only one , were regarded as not having ACS ( negative predictive value 95 % ) . Sensitivity and specificity were 92 and 83 % , respectively . In patients without a history of coronary artery disease ( CAD ) , both the specificity and positive predictive value improved to 100 % ( sensitivity 90 % ; negative predictive value 95 % ) . In patients with neither a history of CAD nor coronary calcification , the diagnostic accuracy of MDCT was 100 % . Conclusions : MDCT has high diagnostic capacity for the early evaluation of ACS , especially in patients without a history of CAD or coronary calcification OBJECTIVE Patients with a low risk of coronary artery disease ( CAD ) presenting to the emergency department ( ED ) with chest pain pose a diagnostic dilemma because a small percentage will suffer an acute myocardial infa rct ion ( MI ) and sudden death . The authors conducted this study to determine whether exercise stress echocardiography ( ESE ) could be used to further support the safe discharge of these low-risk patients . METHODS A convenience sample of patients > or = 30 years of age without a prior cardiac history who presented to an academic community hospital with chest pain , normal initial creatine kinase , and electrocardiography without ischemic changes underwent ESE within 6 + /- 1.7 hours ( mean + /- SD ) . Abnormal ESE was defined as regional wall motion abnormality at rest or after exercise . The ED disposition and three- and six-month follow-up for cardiac events were recorded . This was a prospect i ve observational cohort study . RESULTS Of a total of 149 eligible patients , 145 completed the study . The mean age ( + /-SD ) was 47 + /- 9 years ; 56 % were male . No adverse events were noted during ESE . Seven patients ( 5 % ) had abnormal ESE ( 2 with rest wall motion abnormalities and 5 with exercise-induced wall motion abnormalities ) . Five of the seven underwent cardiac catheterization ; three had CAD . All patients received telephone follow-up at three months and six months . Of the 138 patients with a normal ESE , all were free of cardiac events at three months . One patient had a non-Q-wave MI at six months ( negative predictive value = 99.3 % , 95 % CI = 97.8 % to 100 % ) . CONCLUSIONS Exercise stress echocardiography can be used to evaluate low-risk chest pain patients in the ED . Patients with a normal ESE may be considered for discharge with minimal risk of sequelae BACKGROUND Discharging patients with acute myocardial infa rct ion or unstable angina from the emergency department because of missed diagnoses can have dire consequences . We studied the incidence of , factors related to , and clinical outcomes of failure to hospitalize patients with acute cardiac ischemia . METHODS We analyzed clinical data from a multicenter , prospect i ve clinical trial of all patients with chest pain or other symptoms suggesting acute cardiac ischemia who presented to the emergency departments of 10 U.S. hospitals . RESULTS Of 10,689 patients , 17 percent ultimately met the criteria for acute cardiac ischemia ( 8 percent had acute myocardial infa rct ion and 9 percent had unstable angina ) , 6 percent had stable angina , 21 percent had other cardiac problems , and 55 percent had noncardiac problems . Among the 889 patients with acute myocardial infa rct ion , 19 ( 2.1 percent ) were mistakenly discharged from the emergency department ( 95 percent confidence interval , 1.1 to 3.1 percent ) ; among the 966 patients with unstable angina , 22 ( 2.3 percent ) were mistakenly discharged ( 95 percent confidence interval , 1.3 to 3.2 percent ) . Multivariable analysis showed that patients who presented to the emergency department with acute cardiac ischemia were more likely not to be hospitalized if they were women less than 55 years old ( odds ratio for discharge , 6.7 ; 95 percent confidence interval , 1.4 to 32.5 ) , were nonwhite ( odds ratio , 2.2 ; 1.1 to 4.3 ) , reported shortness of breath as their chief symptom ( odds ratio , 2.7 ; 1.1 to 6.5 ) , or had a normal or nondiagnostic electrocardiogram ( odds ratio , 3.3 ; 1.7 to 6.3 ) . Patients with acute infa rct ion were more likely not to be hospitalized if they were nonwhite ( odds ratio for discharge , 4.5 ; 95 percent confidence interval , 1.8 to 11.8 ) or had a normal or nondiagnostic electrocardiogram ( odds ratio , 7.7 ; 95 percent confidence interval , 2.9 to 20.2 ) . For the patients with acute infa rct ion , the risk-adjusted mortality ratio for those who were not hospitalized , as compared with those who were , was 1.9 ( 95 percent confidence interval , 0.7 to 5.2 ) , and for the patients with unstable angina , it was 1.7 ( 95 percent confidence interval , 0.2 to 17.0 ) . CONCLUSIONS The percentage of patients who present to the emergency department with acute myocardial infa rct ion or unstable angina who are not hospitalized is low , but the discharge of such patients is associated with increased mortality . Failure to hospitalize is related to race , sex , and the absence of typical features of cardiac ischemia . Continued efforts to reduce the number of missed diagnoses are warranted BACKGROUND The inappropriate admission of patients with noncardiac chest pain is an enormous cost to society . Myocardial perfusion imaging ( MPI ) could prove effective in the risk stratification of patients in whom acute coronary syndromes are ruled out by electrocardiography and troponin levels , thanks to its incremental sensitivity beyond that of wall motion ( WM ) criteria for obstructive coronary artery disease , and still maintain the excellent safety profile of dipyridamole-atropine stress echocardiography ( DASE ) . The aim of this study was to test this hypothesis using WM and MPI ( WM + MPI ) in consecutive patients admitted to a chest pain unit . METHODS Patients presenting to a chest pain unit between January and June 2008 with chest pain and in whom acute coronary syndromes had been ruled out by normal electrocardiography and cardiac enzyme levels underwent DASE with the addition of contrast MPI . Four hundred consecutive patients were enrolled . RESULTS WM + MPI result ed in 71 true-positive findings , compared with 46 by st and -alone WM ( P < .05).True-positive results accounted for 46 of 50 positive test results for WM and 71 of 82 positive test results for WM + MPI ( positive predictive value , 92 % vs 87 % ; P = NS ) . In the subset of patients who underwent angiography ( n = 116 ) , the sensitivity , specificity , and accuracy for WM compared with WM + MPI were 63 % versus 97 % ( P < .05 ) , 91 % versus 74 % ( P < .05 ) , and 73 % versus 89 % ( P < .05 ) . CONCLUSIONS The addition of MPI to st and ard DASE increased true-positive test results by > 50 % compared with WM criteria , with a nonsignificant difference in positive predictive value . Twenty-five patients were diagnosed with obstructive coronary artery disease thanks only to isolated MPI abnormalities ; the cardiac origin of their chest pain would have been mistakenly " ruled out " on the basis of the absence of WM abnormalities Abstract Objective Our two-centre prospect i ve study evaluates the usefulness of 64-slice coronary computed tomography ( CCT ) to rule out significant coronary artery stenosis in patients admitted in emergency departments ( ED ) for acute coronary syndromes ( ACS ) with low-to-intermediate risk score . Methods Patients ( 175 ) admitted for acute chest pain ( ACP ) , unmodified electrocardiogram and first troponin measurement within normal ranges were included . A second troponin measurement and a 64-slice CCT within 24 h were performed . Major adverse cardiac events ( MACE ) were recorded during follow-up ( 6 months ± 2 ) . Results 64-slice CCT was either normal or showed non-significant coronary stenosis in the majority of patients ( 78 % ) . 64-slice CCT depicted significant stenosis ( > 50 % diameter ) in 22 % of patient whereas initial clinical and biological evaluation was reassuring . For negative CCTs , elevated troponin at second measurement did not modify the strategy or treatment of patients . No MACEs were noted during follow up . In 12 % of patients CCT identified unsuspected non-coronary abnormalities . Conclusion Our study confirms 64-slice CCT utility to rule out significant coronary artery stenosis in 8/10 patients admitted in ED with ACP or ACS with low-to-intermediate risk score . Early discharge with a negative 64-slice CCT is associated with very low risk of cardiac events at 6 months . Key Points• 64-slice coronary computed tomography ( CCT ) offers a critical role in acute chest pain . • 64-slice CCT allows differentiation between significant and non-significant coronary artery stenosis . • Normal 64-slice CCT allows rapid discharge of patients with ACP . • 64-slice CCT helps make appropriate therapeutic decision in patients with ACP OBJECTIVE We sought to assess the usefulness of stress echocardiography in a chest pain department . METHODS Consecutive patients ( n = 487 ) with nontraumatic chest pain , with no signs of myocardial ischemia on arrival to the emergency department , 6 and 12 hours later , were recruited . RESULTS The sensitivity and specificity of stress echocardiography in the biased sample were 74 % ( 95 % confidence interval [ CI ] 63 - 85 % ) and 65 % ( 95 % CI 44 - 86 % ) . After application of the method of Begg and Greenes to debias the sample , the calculated sensitivity was 24 % ( 95 % CI 19 - 29 % ) and specificity was 94 % ( 95 % CI 91 - 97 % ) . After application of Diamond 's method , sensitivity was 32 % ( 95 % CI 21 - 44 % ) and specificity ( normalcy rate ) was 99 % ( 95 % CI 88 - 100 % ) . CONCLUSIONS Stress echocardiography is an insensitive test when used to detect significant coronary artery stenosis in patients presenting with nontraumatic chest pain with no objective signs of myocardial ischemia PURPOSE To evaluate image quality of low-voltage chest computed tomographic ( CT ) angiography with raw data -based iterative reconstruction ( sonogram-affirmed iterative reconstruction ) in comparison with image quality of st and ard-dose st and ard-voltage filtered back projection ( FBP ) CT . MATERIAL S AND METHODS This prospect i ve study was approved by the institutional review board , and the informed consent requirement was waived . Eighty consecutive patients who were referred for follow-up chest CT angiography underwent reduced-dose CT ( hereafter , T2 examination ) under technical conditions similar to those of the initial examination ( hereafter , T1 examination ) , except the voltage selection was reduced by 20 kV with adaptation of the tube current to ensure a 50 % reduction in CT dose index , and regular FBP was replaced by iterative reconstruction with sonogram-affirmed iterative reconstruction . The two techniques were compared by using paired tests ( Student t test , Wilcoxon test , or McNemar test , according to the nature of variables ) . RESULTS When compared with st and ard-dose T1 studies , reduced-dose T2 images showed : ( a ) significantly less objective noise at the level of the trachea on mediastinal and lung parenchymal images ( P < .001 ) and no significant difference in objective noise at the level of the aorta on mediastinal images ( P = .507 ) ; ( b ) significantly higher signal-to-noise and contrast-to-noise ( P < .001 ) ratios ; ( c ) similar visual perception of noise on mediastinal ( P = .132 ) and lung ( P = .366 ) images , mainly rated as moderate ; and ( d ) similar overall subjective image quality ( P = .405 ) . CONCLUSION Raw data -based iterative reconstruction yielded equivalent subjective and improved objective image quality of low-voltage half-dose CT angiograms compared with st and ard-dose FBP CT images for an average dose-length product of less than 80 mGy · cm in this population . SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120414/-/DC1 The use of ionic contrast media in radiologic examinations may cause a wide variety of anaphylactoid reactions . The aim of this double-blind r and omized study was to determine whether a simple and inexpensive premedication based on an antihistamine could reduce the number of idiosyncratic reactions in 400 patients ( 251 men and 149 women ) without a clinical history of allergy who were to receive an intravenous injection of a low-osmolality iodinated contrast medium . Twelve hours before examination , a group of 200 patients was given one 100-mg tablet of hydroxyzine ; another group of 200 was given a placebo tablet under the same conditions . Results in the two groups were comparable at the .05 level of significance . Twenty-five patients in the placebo group had a reaction ( mainly urticaria ) ; only two patients in the hydroxyzine group had a reaction ( P less than .0001 ; odds ratio , 14.1 ) . No severe reaction occurred in either group . Because hydroxyzine and placebo were allocated at r and om , it is concluded that hydroxyzine reduces the frequency of minor anaphylactoid reactions in patients at low risk CONTEXT Coronary computed tomographic ( CT ) angiography is a noninvasive anatomic test for diagnosis of coronary stenosis that does not determine whether a stenosis causes ischemia . In contrast , fractional flow reserve ( FFR ) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis , but it requires an invasive procedure . Noninvasive FFR computed from CT ( FFR(CT ) ) is a novel method for determining the physiologic significance of coronary artery disease ( CAD ) , but its ability to identify ischemia has not been adequately examined to date . OBJECTIVE To assess the diagnostic performance of FFR(CT ) plus CT for diagnosis of hemodynamically significant coronary stenosis . DESIGN , SETTING , AND PATIENTS Multicenter diagnostic performance study involving 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT , invasive coronary angiography ( ICA ) , FFR , and FFR(CT ) between October 2010 and October 2011 . Computed tomography , ICA , FFR , and FFR(CT ) were interpreted in blinded fashion by independent core laboratories . Accuracy of FFR(CT ) plus CT for diagnosis of ischemia was compared with an invasive FFR reference st and ard . Ischemia was defined by an FFR or FFR(CT ) of 0.80 or less , while anatomically obstructive CAD was defined by a stenosis of 50 % or larger on CT and ICA . MAIN OUTCOME MEASURES The primary study outcome assessed whether FFR(CT ) plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 1-sided 95 % confidence interval of this estimate exceeded 70 % . RESULTS Among study participants , 137 ( 54.4 % ) had an abnormal FFR determined by ICA . On a per-patient basis , diagnostic accuracy , sensitivity , specificity , positive predictive value , and negative predictive value of FFR(CT ) plus CT were 73 % ( 95 % CI , 67%-78 % ) , 90 % ( 95 % CI , 84%-95 % ) , 54 % ( 95 % CI , 46%-83 % ) , 67 % ( 95 % CI , 60%-74 % ) , and 84 % ( 95 % CI , 74%-90 % ) , respectively . Compared with obstructive CAD diagnosed by CT alone ( area under the receiver operating characteristic curve [ AUC ] , 0.68 ; 95 % CI , 0.62 - 0.74 ) , FFR(CT ) was associated with improved discrimination ( AUC , 0.81 ; 95 % CI , 0.75 - 0.86 ; P < .001 ) . CONCLUSION Although the study did not achieve its prespecified primary outcome goal for the level of per-patient diagnostic accuracy , use of noninvasive FFR(CT ) plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination vs CT alone for the diagnosis of hemodynamically significant CAD when FFR determined at the time of ICA was the reference st and ard |
2,138 | 29,527,342 | There was supportive evidence that cervical screening and hepatitis B immunisation prevent cancer in LLMICs . | Background Non-communicable diseases ( NCDs ) are the leading cause of death and disability worldwide , with low-income and middle-income countries experiencing a disproportionately high burden .
Since 2010 WHO has promoted 24 highly cost-effective interventions for NCDs , dubbed ' best buys ' .
It is unclear whether these interventions have been evaluated in low-income and lower-middle-income countries ( LLMICs ) .
Aim To systematic ally review research on interventions aligned to WHO ' best buys ' for NCDs in LLMICs . | Background : Tobacco smoking is an integral part of prison life and an established part of the culture . Little attention has been paid to prevention of smoking in prison . Approximately 70–80 % of prisoners have been identified as current smokers . Aim : To assess the effectiveness of smoking cessation intervention among male prisoners at Central Jail , Bangalore city . Aim : To assess the effectiveness of smoking cessation intervention among male prisoners at Central Jail , Bangalore city . Material s and Methods : A r and omized controlled trial was planned among male prisoners in Central Jail , Bangalore city . There were 1600 convicted prisoners . A self-administered question naire was given to the prisoners to assess their smoking behavior by which prevalence of tobacco smoking was found . Exactly 1352 tobacco users were studied . Among them , there were 1252 smokers . Based on inclusion criteria and informed consent given by the prisoners , a sample of 600 was chosen for the study by systematic r and om sampling . Among the 600 prisoners , 300 were r and omly selected for the study group and 300 for the control group . Results : Prevalence of tobacco smoking among the prisoners was 92.60 % . In the present study , after smoking cessation intervention , 17 % showed no change in smoking , 21.66 % reduced smoking , 16 % stopped smoking , and 45.33 % relapsed ( P < 0.0001 ) at the end of 6-month follow-up in the study group . Conclusion : Tobacco use was high among the prisoners . Tobacco reduction is possible in the prison even if the living conditions are not favorable . Relatively high rate of relapse in our study indicates that some policies should be adopted to improve smokers ’ information on consequences of tobacco on health and motivational intervention should be added to prisoners INTRODUCTION Tobacco use in low- to middle-income countries is a major public health concern for both smokers and those exposed to environmental tobacco smoke ( ETS ) . Egypt has made important strides in controlling tobacco use , but smoking and ETS remain highly prevalent . This r and omized intervention sought to improve the target population 's knowledge regarding the hazards of smoking and ETS and to change attitudes and smoking behaviors within the community and the household . METHODS In this 2005 - 2006 study in Egypt 's Qalyubia governorate , trained professionals visited schools , households , mosques , and health care centers in rural villages r and omly selected for the intervention to discuss the adverse effects of smoking and ETS exposure and ways to reduce one 's ETS exposure . Data collected in interviewer-facilitated surveys before and after the intervention period were analyzed in pairwise comparisons with data from control villages to assess the effectiveness of the intervention in achieving its aims . RESULTS The intervention group showed a greater increase in underst and ing the dangers associated with smoking cigarettes and waterpipes and became more proactive in limiting ETS exposure by asking smokers to stop , avoiding areas with ETS , and enacting smoking bans in the home . However , the intervention had little to no impact on the number of smokers and the amount of tobacco smoked . CONCLUSIONS Results are consistent with previous studies showing that changing smokers ' behavior can be difficult , but community-wide efforts to reduce ETS exposure through smoking bans , education , and empowering people to ask smokers to stop are effective . The method can be generalized to other setting BACKGROUND In India , tobacco consumption is responsible for one of the highest rates of oral cancer in the world , the annual oral cancer incidence is steadily increasing among young tobacco users . Studies have documented efforts taken by physicians , doctors and even dentists , in the form of individual or group counseling to curb tobacco use in smoke or smokeless form . However , which one is more effective , still remains an unanswered question . The aim of the study was to compare the effectiveness of individual and group counseling for cessation of the tobacco habit amongst industrial workers in Pune and to compare quit rates . MATERIAL S AND METHODS An interventional study design was selected for 150 industrial workers which were stratified r and omly into three groups ( control , individual and group counseling groups ) and interventions were provided to individual and group counseling groups over a period of six months , which were then compared with the control group that received brief intervention at the start of the study . RESULTS There was significant difference in the quit rates of the participants in the individual counseling group ( ICG ) and group counseling group ( GCG ) when compared at 6 months with the control counseling group ( CCG ) . In the individual counseling group was 6 % while in group counseling group it was 7.5 % after six months of counseling . CONCLUSIONS No conclusion could be drawn whether individual or group counseling were better interms of quit rates . Individual and group counseling groups were definitely better than the control group when compared at 3 and 6 months , respectively Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background In response to India 's growing tobacco epidemic , strategies are needed to decrease tobacco use among Indian youth , particularly among those who are economically disadvantaged . The objective of this study was to assess the effectiveness of a school-based life-skills tobacco control program for youth of low socio-economic status in Mumbai and the surrounding state of Maharashtra . We hypothesized that compared to youth in control schools , youth exposed to the program would have greater knowledge of effects of tobacco use ; be more likely to take action to prevent others from using tobacco ; demonstrate more positive life skills and attitudes ; and be less likely to report tobacco use . Methods / Findings Using a quasi-experimental design , we assessed program effectiveness by comparing 8th and 9th grade students in intervention schools to 8th grade students in comparable schools that did not receive the program . Across all schools , 1851 students completed a survey that assessed core program components in early 2010 . The program consisted of activities focused on building awareness about the hazards of tobacco , developing life skills , and advocacy development . The primary outcome measure was self-reported tobacco use in the last 30 days . Findings indicate that 4.1 % of 8th grade intervention students ( OR = 0.51 ) and 3.6 % of 9th grade intervention students ( OR = 0.33 ) reported using tobacco at least once in the last 30 days , compared to 8.7 % of students in the control schools . Intervention group students were also significantly more knowledgeable about tobacco and related legislation , reported more efforts to prevent tobacco use among others , and reported stronger life skills and self-efficacy than students in control schools . Limitations to the study include schools not being r and omly assigned to condition and tobacco use being measured by self-report . Conclusions This program represents an effective model of school-based tobacco use prevention that low-income schools in India and other low- and middle-income countries can replicate BACKGROUND Cervical cancer is the leading cause of cancer mortality among women in India . Because Pap smear screening is not feasible in India , we need to develop effective alternatives . METHODS A cluster-r and omized controlled study was initiated in 1998 in Mumbai , India , to investigate the efficacy of visual inspection with acetic acid ( VIA ) performed by primary health workers in reducing cervical cancer mortality . Four rounds of cancer education and VIA screening were conducted at 24-month intervals in the screening group , whereas cancer education was offered once at entry to the control group . The study was planned for 16 years to include four screening rounds followed by four monitoring rounds . We present results after 12 years of follow-up . Poisson regression method was used to calculate the rate ratios ( RRs ) ; two-sided χ(2 ) was used to calculate the probability . RESULTS We recruited 75360 women from 10 clusters in the screening group and 76178 women from 10 comparable clusters in the control group . In the screening group , we achieved 89 % participation for screening and 79.4 % compliance for diagnosis confirmation . The incidence of invasive cervical cancer was 26.74 per 100000 ( 95 % confidence interval [ CI ] = 23.41 to 30.74 ) in the screening group and 27.49 per 100000 ( 95 % CI = 23.66 to 32.09 ) in the control group . Compliance to treatment for invasive cancer was 86.3 % in the screening group and 72.3 % in the control group . The screening group showed a statistically significant 31 % reduction in cervical cancer mortality ( RR = 0.69 ; 95 % CI = 0.54 to 0.88 ; P = .003 ) . CONCLUSIONS VIA screening by primary health workers statistically significantly reduced cervical cancer mortality . Our study demonstrates the efficacy of an easily implementable strategy that could prevent 22000 cervical cancer deaths in India and 72600 deaths in re source -poor countries annually Background India has the second largest diabetic population ( 61 million ) and tobacco users ( 275 million ) in the world . Data on smoking cessation among diabetic patients are limited in low and middle income countries . The objective of the study was to document the effectiveness of diabetic specific smoking cessation counseling by a non-doctor health professional in addition to a cessation advice to quit , delivered by doctors . Methods In our parallel-group r and omized controlled trial , we selected 224 adult diabetes patients aged 18 years or older who smoked in the last month , from two diabetes clinics in South India . Using a computer generated r and om sequence with block size four ; the patients were r and omized equally into intervention-1 and intervention-2 groups . Patients in both groups were asked and advised to quit smoking by a doctor and distributed diabetes specific education material s. The intervention-2 group received an additional diabetes specific 30 minutes counseling session using the 5As ( Ask , Advise , Assess , Assist and Arrange ) , and 5 Rs ( Relevance , Risks , Rewards , Roadblocks and Repetition ) from a non-doctor health professional . Follow up data were available for 87.5 % of patients at six months . The Quit Tobacco International Project is supported by a grant from the Fogarty International Centre of the US National Institutes of Health (RO1TW005969 - 01).The primary outcomes were quit rate ( seven day smoking abstinence ) and harm reduction ( reduction of the number of cigarettes / bidis smoked per day > 50 % of baseline use ) at six months . Results In the intention to treat analysis , the odds for quitting was 8.4 [ 95 % confidence interval ( CI ) : 4.1 - 17.1 ] for intervention-2 group compared to intervention-1 group . Even among high level smokers the odds of quitting was similar . The odds of harm reduction was 1.9 ( CI : 0.8 - 4.1 ) for intervention-2 group compared to intervention-1 group . Conclusions The value addition of culturally sensitive diabetic specific cessation counseling sessions delivered by non-doctor health professional was an impressive and efficacious way of preventing smoking related diabetic complications . Trial Registration Clinical Trial Registry of India ( CTRI/2012/01/002327 OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India BACKGROUND Prevalence of tobacco use is higher in the rural than urban areas of India . Unlike tobacco cessation clinics located in urban areas , community-based smoking cessation intervention has the potential to reach a wider section of the community to assist in smoking cessation in the rural setting . The present study aim ed to assess the effectiveness of a cessation intervention in rural Kerala state , India . MATERIAL S AND METHODS Current daily smoking resident males in the age group 18 - 60 years from four community development blocks in rural Kerala were r and omly allocated to intervention and control groups . The intervention group received multiple approaches in which priority was given to face-to-face interviews and telephone counselling . Initially educational material s on tobacco hazards were distributed . Further , four rounds of counselling sessions were conducted which included a group counselling with a medical camp as well as individual counselling by trained medical social workers . The control group received general awareness training on tobacco hazards along with an anti-tobacco leaflet . Self-reported smoking status was assessed after 6 and 12 months . Factors associated with tobacco cessation were estimated using binomial regression method . RESULTS Overall prevalence of smoking abstinence was 14.7 % in the intervention and 6.8 % in the control group ( Relative risk : 1.85 , 95 % CI : 1.05 , 3.25 ) . A total of 41.3 % subjects in the intervention area and 13.6 % in the control area had reduced smoking by 50 % or more at the end of 12 months . Lower number of cigarettes/ bidi used , low nicotine dependence and consultation with a doctor for a medical ailment were the statistically significant predictors for smoking cessation . CONCLUSIONS Rigorous approaches for smoking cessation programmes can enhance quit rates in smoking in rural areas of India OBJECTIVES We assessed a school-based intervention design ed to promote tobacco control among teachers in the Indian state of Bihar . METHODS We used a cluster-r and omized design to test the intervention , which comprised educational efforts , tobacco control policies , and cessation support and was tailored to the local social context . In 2009 to 2011 , we r and omly selected 72 schools from participating school districts and r and omly assigned them in blocks ( rural or urban ) to intervention or delayed-intervention control conditions . RESULTS Immediately after the intervention , the 30-day quit rate was 50 % in the intervention and 15 % in the control group ( P = .001 ) . At the 9-month postintervention survey , the adjusted 6-month quit rate was 19 % in the intervention and 7 % in the control group ( P = .06 ) . Among teachers employed for the entire academic year of the intervention , the adjusted 6-month abstinence rates were 20 % and 5 % , respectively , for the intervention and control groups ( P = .04 ) . CONCLUSIONS These findings demonstrate the potent impact of an intervention that took advantage of social re sources among teachers , who can serve as role models for tobacco control in their communities AIMS To examine the associations between alcohol control policies in four regulatory domains with alcohol consumption in low- and middle-income countries ( LAMICs ) , controlling for country-level living st and ards and drinking patterns . DESIGN Cross-sectional analyses of individual-level alcohol consumption survey data and country-level alcohol policies using multi-level modeling . SETTING Data from 15 LAMICs collected in the Gender , Alcohol , and Culture : an International Study ( GENACIS ) data set . PARTICIPANTS Individuals aged 18 - 65 years . MEASUREMENTS Alcohol policy data compiled by the World Health Organization ; individual-level current drinking status , usual quantity and frequency of drinking , binge drinking frequency and total drinking volume ; gross domestic product based on purchasing power parity ( GDP-PPP ) per capita ; detrimental drinking pattern scale ; and age and gender as individual-level covariates . FINDINGS Alcohol policies regulating the physical availability of alcohol , particularly those concerning business hours or involving a licensing system for off-premises alcohol retail sales , as well as minimum legal drinking age , were the most consistent predictors of alcohol consumption . Aggregate relative alcohol price levels were associated inversely with all drinking variables ( P < 0.05 ) except drinking volume . Greater restrictions on alcohol advertising , particularly beer advertising , were associated inversely with alcohol consumption ( P < 0.05 ) . Policies that set legal blood alcohol concentration ( BAC ) limits for drivers and r and om breath testing to enforce BAC limits were not associated significantly with alcohol consumption . CONCLUSIONS Alcohol policies that regulate the physical availability of alcohol are associated with lower alcohol consumption in low- and middle-income countries OBJECTIVE To reduce tobacco use among adolescents . METHODS Thirty schools in New Delhi , India , were r and omly assigned to 3 conditions : school-based and family-based intervention , school-based intervention only , or control group . Students were in the seventh grade at pretest ( N = 4,776 ) . The smoking intervention included posters , booklets , classroom activities , debates , and a signature campaign . The family intervention involved home activities . The survey measured tobacco knowledge , attitudes , offers , use , and intentions . RESULTS Intervention students were significantly less likely than controls to have been offered , received , experimented with , or have intentions to use tobacco . CONCLUSION The project had a significant impact on tobacco use Because of the high prevalence of hepatitis B virus ( HBV ) infection in The Gambia , HBV vaccination has been incorporated into the national exp and ed programme on immunisation . We have assessed the efficacy of the vaccine against HBV infection and chronic carriage by examining 720 3 - 4-year-old children who had received the vaccine in infancy and 816 who had not received it . The vaccine was 84 % ( 95 % CI 78 - 89 % ) effective against infection and 94 % ( 84 - 98 % ) effective against chronic carriage . Vaccinated infants of mothers positive for hepatitis B surface and e antigens were at greater risk of breakthrough infection and chronic carriage than infants of uninfected mothers . The high vaccine efficacy against the HBV carrier state , the main risk factor for the development of chronic liver disease and liver cancer , offers hope that the prevalence of these diseases may be reduced in the future BACKGROUND Exposure to second-h and smoke is a threat to children 's health . We developed a school-based smoke-free intervention ( SFI ) to support families in implementing smoke-free homes in Bangladesh , and gathered preliminary evidence of its effectiveness . METHODS A feasibility cluster r and omized controlled trial of SFI was conducted in 24 schools in Mirpur , an urban area within Dhaka . Using simple stratified r and omization , schools were allocated to : Arm A ( SFI only ) , Arm B ( SFI plus reminders ) , and Arm C ( the control group ) . A total of 781 year-5 children ( 10 - 12 years old ) in the consenting schools , participated in the study . Outcomes including " smoke-free homes " and " social visibility " that is , not smoking in front of children at home were assessed through question naire-based children 's surveys , administered by research ers , at baseline and at weeks 1 , 12 , 27 , and 52 in all arms . RESULTS " Smoke-free homes " were significantly higher in Arm A ( odds ratio [ OR ] = 4.8 ; 95 % CI = 2.6 - 9.0 ) and in Arm B ( OR = 3.9 ; 95 % CI = 2.0 - 7.5 ) than in Arm C , when controlled for the baseline levels , at year 1 . Similarly , " social visibility " was significantly reduced in Arm A ( OR = 5.8 ; 95 % CI = 2.8 - 11.7 ) and in Arm B ( OR = 7.2 ; 95 % CI = 3.3 - 15.9 ) than Arm C , when controlled for the baseline levels , at year 1 . We observed an increasing trend ( Cochrane Armitage test statistic [ Z ] = 3.8 ; p < .0001 ) in homes becoming smoke-free with increasing intensity of the intervention ( control < Arm A < Arm B ) , and a decreasing trend ( Z = -5.13 ; p < .0001 ) in social visibility at homes . CONCLUSION SFI has the potential to encourage children to negotiate a smoke-free environment in their homes Type 2 diabetes mellitus is associated with a marked increase in the risk of coronary heart disease ( CHD ) or stroke ( by a factor of two to three compared with non-diabetic patients ) , and cardiovascular disease ( CVD ) accounts for the majority of deaths among patients with diabetes . A new fixed dose combination containing atorvastatin 10 mg + metformin SR 500 mg is being introduced in the Indian market for the treatment of dyslipidaemia in diabetic patients . The present study was therefore undertaken to assess efficacy , safety and tolerability of a fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg in adult Indian patients with diabetic dyslipidaemia . The final protocol was approved by relevant ethics committee before the initiation of study . Informed consent was obtained from all the patients prior to enrollment in study . The total duration of study was 14 weeks including two weeks dietary run in period . Patients fulfilling the selection criteria received a single oral tablet of fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg once daily for 12 weeks . The primary efficacy parameters were assessed by evaluating reduction in fasting and postpr and ial plasma glucose concentration levels at baseline and thereafter at each follow up visit at 2 , 4 , 8 and 12 weeks and plasma lipid profile and glycosylated Hb levels at baseline and end of study . The secondary efficacy parameters were assessed by evaluating percentage change from baseline at the end of the study ( week 12 ) in the plasma concentration of the various lipid parameters such as total , HDL- , LDL- and very low density (VLDL)-cholesterol , triglycerides , Apo B , Apo A1 , TC/LDL ratio , LDL/ HDL ratio , and percentage of patients achieving LDL-cholesterol goals as per NCEP ATP III guidelines . A total of 213 patients were enrolled in the study . Of these seven patients were lost to follow-up and considered as drop-outs . Therapy with the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg result ed in a significant reduction in the mean plasma fasting and postpr and ial glucose levels ( 35 and 38.8 % respectively ) . There was a steep fall in the HbA1c levels from baseline levels of 8.76 % to 6.74 % ( 23.1 % ) . There was also a significant ( p < 0.05 ) reduction in mean total cholesterol ( 31.2 % ) , LDL cholesterol ( 35.4 % ) , VLDL-cholesterol ( 19.6 % ) and a significant increase HDL-cholesterol ( 9.5 % ) . Thus there appeared to be trend towards reducing atherosclerosis following therapy with the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg . Mean body mass index was significantly reduced in the patients in the present study following therapy with the study drugs . The fixed dose combination of atorvastatin with metformin was well tolerated with mostly gastro-intestinal adverse events being reported in the current study . Moreover , most of the adverse events were mild to moderate in intensity and disappeared with continued treatment . In conclusion , the results of the present study suggest that , the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg is efficacious and well tolerated therapeutic modality in patients with diabetic dyslipidaemia . Furthermore this combination offers dosage convenience to the patient and by virtue of its dual mode of action is a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidaemia BACKGROUND Cervical cancer is the most common cancer among women in developing countries . We assessed the effect of screening using visual inspection with 4 % acetic acid ( VIA ) on cervical cancer incidence and mortality in a cluster r and omised controlled trial in India . METHODS Of the 114 study clusters in Dindigul district , India , 57 were r and omised to one round of VIA by trained nurses , and 57 to a control group . Healthy women aged 30 to 59 years were eligible for the study . Screen-positive women had colposcopy , directed biopsies , and , where appropriate , cryotherapy by nurses during the screening visit . Those with larger precancerous lesions or invasive cancers were referred for appropriate investigations and treatment . Cervical cancer incidence and mortality in the study groups were analysed and compared using Cox regression taking the cluster design into account , and analysis was by intention to treat . The primary outcome measures were cervical cancer incidence and mortality . RESULTS Of the 49,311 eligible women in the intervention group , 31,343 ( 63.6 % ) were screened during 2000 - 03 ; 30,958 control women received the st and ard care . Of the 3088 ( 9.9 % ) screened positive , 3052 had colposcopy , and 2539 directed biopsy . Of the 1874 women with precancerous lesions in the intervention group , 72 % received treatment . In the intervention group , 274,430 person years , 167 cervical cancer cases , and 83 cervical cancer deaths were accrued compared with 178,781 person-years , 158 cases , and 92 deaths and in the control group during 2000 - 06 ( incidence hazard ratio 0.75 [ 95 % CI 0.55 - 0.95 ] and mortality hazard ratio 0.65 [ 0.47 - 0.89 ] ) . INTERPRETATION VIA screening , in the presence of good training and sustained quality assurance , is an effective method to prevent cervical cancer in developing countries BACKGROUND The Indian government enacted ' The cigarettes and other tobacco products act , 2003 ' ( COTPA ) , which prohibits smoking in public places . AIM To vali date the efficacy of the Act of 2003 , enacted by the Government of India , to prevent secondh and smoking in public places . SETTING S AND DESIGN The study is based on a non-r and om sample survey of 2,600 bus passengers carried out in the premises of three mega public road transport organizations in Karnataka state , India , in June 2007 . METHODS AND MATERIAL The information was gathered through administration of structured schedules . A sample of 1,000 each for the terminus of Bangalore Metropolitan Transport Corporation ( BMTC ) and Karnataka State Road Transport Corporation ( KSRTC ) in Bangalore and , 600 for North West Karnataka Road Transport Corporation ( NWKRTC ) in Hubli-Dharwad city was distributed proportionately according to the number of platforms in each terminus . STATISTICAL ANALYSIS USED Simple Averages . RESULTS There is some reduction in smoking in general as perceived by 69 % of the passengers as compared to the scenario a year before the enactment of COTPA . The observed smoking is lower in the bus premises of BMTC where there is strict regulation , and higher in the bus premises of NWKRTC , which has not taken any regulatory measures . CONCLUSIONS Knowing smoking is banned in public places can itself create awareness depending on the coverage extended by media and implementing an agency to reach the public . The implementation of an act depends on the willingness of stakeholders to act upon it . The implementation of COTPA as done by BMTC could well become a role model for replication elsewhere , if BMTC can strive harder to accomplish a 100 % smoke-free zone Background — In rural areas in China and India , the cardiovascular disease burden is high but economic and healthcare re sources are limited . This study ( the Simplified Cardiovascular Management Study [ SimCard ] ) aims to develop and evaluate a simplified cardiovascular management program delivered by community health workers with the aid of a smartphone-based electronic decision support system . Methods and Results — The SimCard study was a yearlong cluster-r and omized , controlled trial conducted in 47 villages ( 27 in China and 20 in India ) . Recruited for the study were 2086 individuals with high cardiovascular risk ( aged ≥40 years with self-reported history of coronary heart disease , stroke , diabetes mellitus , and /or measured systolic blood pressure ≥160 mm Hg ) . Participants in the intervention villages were managed by community health workers through an And roid-powered app on a monthly basis focusing on 2 medication use and 2 lifestyle modifications . In comparison with the control group , the intervention group had a 25.5 % ( P<0.001 ) higher net increase in the primary outcome of the proportion of patient-reported antihypertensive medication use pre- and post-intervention . There were also significant differences in certain secondary outcomes : aspirin use ( net difference : 17.1 % ; P<0.001 ) and systolic blood pressure ( –2.7 mm Hg ; P=0.04 ) . However , no significant changes were observed in the lifestyle factors . The intervention was culturally tailored , and country-specific results revealed important differences between the regions . Conclusions — The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in re source -poor setting s in China and India . Larger trials in more places are needed to ascertain the potential impacts on mortality and morbidity outcomes . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01503814 |
2,139 | 24,919,003 | CONCLUSION It was not possible to reveal any evidence for benefits using DPF compared to rigid fixation in surgery for lumbar spine | OBJECTIVE The objective of this review is to reveal the quality of published data and the effect size of DPFs compared to rigid fixation in lumbar spine .
SUMMARY OF BACKGROUND DATA since 2002 , several dynamic pedicle fixation ( DPF ) systems have been developed with the aim to stabilize the spine without the undesirable effects of rigid lumbar spine fixation .
Nearly ten years later , there are several studies on these dynamic systems . | Study Design . Prospect i ve clinical study . Objective . To test whether elastic stabilization with the Dynesys system ( Zimmer Spine , Minneapolis , MN ) provides enough stability to prevent further progression of spondylolisthesis as well as instability after decompression for spinal stenosis with degenerative spondylolisthesis . Summary of Background Data . In spinal stenosis with degenerative spondylolisthesis , decompression and fusion is widely recommended . However , patients have donor site pain . In 1994 , a dynamic transpedicular system ( Dynesys ) was introduced to the market , stating that stabilization is possible without bone grafting . Methods . A total of 26 patients ( mean age 71 years ) with lumbar spinal stenosis and degenerative spondylolisthesis underwent interlaminar decompression and dynamic stabilization with the Dynesys system . Minimum follow-up was 2 years . Operative data , clinical outcome , and plain and flexion/extension radiographs were obtained and compared to preoperative and postoperative data . Results . Mean leg pain decreased significantly ( P < 0.01 ) , and mean walking distance improved significantly to more than 1000 m ( P < 0.01 ) . There were 5 patients ( 21 % ) who still had some claudication . A total of 21 patients ( 87.5 % ) would undergo the same procedure again . Radiographically , no significant progression of spondylolisthesis could be detected . The implant failure rate was 17 % , and none of them were clinical ly symptomatic . Conclusions . In elderly patients with spinal stenosis with degenerative spondylolisthesis , dynamic stabilization with the Dynesys system in addition to decompression leads to similar clinical results as seen in established protocol s using decompression and fusion with pedicle screws . It maintains enough stability to prevent further progression of spondylolisthesis or instability . With the Dynesys system , no bone grafting is necessary , therefore , donor site morbidity can be avoided Abstract . Various forms of lumbar instability require a surgical stabilization . As an alternative to fusion , a mobile , dynamic stabilization restricting segmental motion would be advantageous in various indications , allowing greater physiological function and reducing the inherent disadvantages of rigid instrumentation and fusion . The dynamic neutralization system for the spine ( Dynesys ) is a pedicle screw system for mobile stabilization , consisting of titanium alloy screws connected by an elastic synthetic compound , controlling motion in any plane ( non-fusion system ) . This prospect i ve , multi-center study evaluated the safety and efficacy of Dynesys in the treatment of lumbar instability conditions , evaluating pre- and post-operative pain , function , and radiological data on a consecutive series of 83 patients . Indications consisted of unstable segmental conditions , mainly combined with spinal stenosis ( 60.2 % ) and with degenerative discopathy ( 24.1 % ) , in some cases with disc herniation ( 8.4 % ) , and with revision surgery ( 6.0 % ) . Thirty-nine patients additionally had degenerative spondylolisthesis , and 30 patients had undergone previous lumbar surgery . In 56 patients instrumentation was combined with direct decompression . The mean age at operation was 58.2 ( range 26.8–85.3 ) years ; the mean follow-up time was 38.1 months ( range 11.2–79.1 months ) . There were nine complications unrelated to the implant , and one due to a screw malplacement . Four of them required an early surgical reintervention . Additional lumbar surgery in the follow-up period included : implant removal and conversion into spinal fusion with rigid instrumentation for persisting pain in three cases , laminectomy of an index segment in one case and screw removal due to loosening in one case . In seven cases , radiological signs of screw loosening were observed . In seven cases , adjacent segment degeneration necessitated further surgery . Mean pain and function scores improved significantly from baseline to follow-up , as follows : back pain scale from 7.4 to 3.1 , leg pain scale from 6.9 to 2.4 , and Oswestry Disability Index from 55.4 % to 22.9 % . These study results compare well with those obtained by conventional procedures ; in addition to which , mobile stabilization is less invasive than fusion . Long-term screw fixation is dependent on correct screw dimension and proper screw positioning . The natural course of polysegmental disease in some cases necessitates further surgery as the disease progresses . Dynamic neutralization proved to be a safe and effective alternative in the treatment of unstable lumbar conditions Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration OBJECTIVES The aim of this study was to evaluate the outcome of wide surgical decompression and concomitant posterior instrumentation in patients with degenerative lumbar spinal stenosis . METHODS Thirty-seven consecutive patients ( 14 men , 23 women ; mean age 64 years ; range 36 to 82 years ) with degenerative lumbar spinal stenosis were prospect ively evaluated following surgical treatment with spinal decompression and concomitant instrumented posterior fusion . The mean duration of symptoms before surgery was 24 months ( range 12 to 60 months ) . Preoperatively , six patients had degenerative spondylolisthesis ( grade 1 ) and two patients had degenerative lumbar scoliosis . Decompression was performed at one level in four patients , at two levels in 16 patients , at three levels in 11 patients , and at four levels in six patients . Discectomy was also performed in seven patients . Preoperatively and postoperatively , the patients were assessed by the Oswestry Disability Index and a visual analog scale for overall pain ( leg and low back pain ) . The satisfaction level of the patients for surgical outcome was also question ed . The mean follow-up period was 4.6 years ( range 1 to 7 years ) . RESULTS Preoperatively , the mean Oswestry Disability Index score was 60.5 % and the mean overall pain score was 7.5 . Postoperatively , the Oswestry Disability Index score significantly decreased to 36.8 % and the overall pain score significantly decreased to 3.5 ( p<0.001 ) . Preoperative and postoperative walking distances of the patients were as follows , respectively : more than 1,000 meters ( 6 and 14 patients ) , 500 to 1,000 meters ( 5 and 7 patients ) , less than 500 meters ( 26 and 16 patients ) . Twenty patients did not use any analgesics and eight patients used analgesics on a weekly basis . Twenty-six patients were satisfied with the surgical outcome , nine patients were somewhat satisfied , and two patients were dissatisfied . Overall , the outcomes were excellent to good in 22 patients ( 59.5 % ) . None of the patients required revision surgery . CONCLUSION Most patients with degenerative lumbar spinal stenosis benefit from decompressive surgery . Patients with long-st and ing preoperative symptoms and concomitant diseases often have poor results and are less satisfied with the postoperative outcome Study Design . Prospect i ve comparative r and omized clinical and radiologic study . Objective . This study was conducted to compare the short-term effects of rigid versus semirigid and dynamic instrumentation on the global and segmental lumbar spine profile , subjective evaluation of the result , and the associated complications . Background Data . Lumbar spine fusion with rigid instrumentation for degenerative spinal disorders seems to increase the fusion rate . However , rigid instrumentation may be associated with some undesirable effects , such as increased low back pain following decrease of lumbar lordosis , fracture of the vertebral body and pedicle , pedicle screw loosening , and adjacent segment degeneration . The use of semirigid and dynamic devices has been advocated to reduce such adverse effects of the rigid instrumentation and thus to achieve a more physiologic bony fusion . Material s and Methods . This study compared 3 equal groups of 45 adult patients , who underwent primary decompression and stabilization for symptomatic degenerative lumbar spinal stenosis . The patients of each group were r and omly selected and received either the rigid ( Group A ) , or semirigid ( Group B ) , or dynamic ( Group C ) spinal instrumentation with formal decompression and fusion . The mean ages of the patients who received rigid , semirigid , and dynamic instrumentation were 65 ± 9 , 59 ± 16 , and 62 ± 10 years , respectively . All patients had detailed roentgenographic study including computed tomography scan and magnetic resonance imaging before surgery to the latest follow-up observation . The following roentgenographic parameters were measured and compared in all spines : lumbar lordosis ( L1–S1 ) , total lumbar lordosis ( T12–S1 ) , sacral tilt , distal lordosis ( L4–S1 ) , segmental lordosis , vertebral inclination , and disc index . The SF-36 health survey and Visual Analogue Scale was used before surgery to the latest evaluation . Results . All patients were evaluated after a mean follow-up of 47 ± 14 months . Both lumbar and total lordosis correction did not correlate with the number of the levels instrumented in any group . Total lordosis was slightly decreased after surgery ( 3 % , P < 0.05 ) in Group C. The segmental lordosis L2–L3 was increased after surgeryby8.5 % ( P < 0.05 ) in Group C , whereas the segmentallordosis L4–L5 was significantly decreased in Group A and C by 9.8 % ( P = 0.01 ) and 16.2 % ( P < 0.01 ) , respectively . The disc index L2–L3 was decreased after surgery in Group A and C by 17 % ( P < 0.05 ) and 23.5 % ( P < 0.05 ) , respectively . The disc index L3–L4 was increased in Group C by 18.74 % ( P < 0.01 ) . The disc index L4–L5 was after surgery decreased in all 3 groups : Group A by 21 % ( P = 0.01 ) , Group B by 13 % ( P < 0.05 ) , and Group C by 13.23 % ( P < 0.05 ) . The disc index L5–S1 was significantly decreased in Group B by 13 % ( P < 0.05 ) . The mean preoperative scores of the SF-36 before surgery were 11 , 14 , and 13 for Groups C , B , and A , respectively . In the first year after surgery , there was a significant increase of the preoperative SF-36 scores to 65 , 61 , and 61 for Groups C , B , and A , respectively , that represents an improvement of 83 % , 77 % , and 79 % , respectively . In the second year after surgery and thereafter , there was a further increase of SF-36 scores of 19 % , 23 % , and 21 % for Groups C , B , and A , respectively . The mean preoperative scores of Visual Analogue Scale for low back pain for Groups C , B , and A were 5 , 4.5 , and 4.3 , respectively , and decreased after surgery to 1.9 , 1.5 , and 1.6 , respectively . The mean preoperative scores of the Visual Analogue Scale for leg pain for Groups C , B , and A were 7.6 , 7.1 , and 6.9 , respectively , and decreased after surgery to 2.5 , 2.5 , and 2.7 , respectively . All fusions healed radiologically within the expected time in all three groups without pseudarthrosis or malunion . Delayed hardware failure ( 1 screw and 2 rod breakages ) 1 year and 18 months after surgery without radiologic pseudarthrosis was observed in 2 patients in Group C. Asymptomatic radiolucent areas were shown around pedicle screws in the pedicles L5 and S1 in 2 , 3 , and 4 cases in Group C , A , and B , respectively . There was no adjacent segment degeneration in any spine until the last evaluation . Discussion and Conclusion . This comparative study showed that all three instrumentations applied over a short area for symptomatic degenerative spinal stenosis almost equally after surgery maintained the preoperative global and segmental sagittal profile of the lumbosacral spine and was followed by similarly significant improvement of both self- assessment and pain scores . Hardware failure occurred at a low rate following dynamic instrumentation solely without radiologically visible pseudarthrosis or loss of correction . Because of the similar clinical and radiologic data in all three groups and the relative small number of patients that were included in each group , it is difficult for the authors to make any recommendation in favor of any instrumentation |
2,140 | 23,761,014 | The use of telemedicine for post-stroke care is nascent and is primarily focused on post-stroke rehabilitation | Telemedicine for acute stroke care is supported by a literature base .
It remains unclear whether or not the use of telemedicine for other phases of stroke care is beneficial . | This study explored the equivalence of physical function assessment by physical therapists ( PTs ) during face-to-face and remote administration of the European Stroke Scale ( ESS ) and the Functional Reach Test ( FRT ) to 26 subjects with a history of stroke . Patients were r and omized to remote or face-to-face administration groups . Each patient was simultaneously rated by both the face-to-face and remote PTs . The PTs were blinded to each other 's results . Equivalence was set at the 95 % limits of agreement . When the face-to-face PT directed the patient , the two PTs reported equivalent values in more than 90 % of the patients for the FRT and for all ESS components , with the exception of gait ( 83 % ) and maintaining leg position ( 85 % ) . When the remote PT directed the patient , the two PTs reported equivalent values in more than 90 % of the patients for the FRT and more than 83 % for all ESS components . Televideo assessment of function by PTs is substantially equivalent to a face-to-face encounter BACKGROUND AND PURPOSE Telemedicine can disseminate vascular neurology expertise and optimize recombinant tissue plasminogen activator ( rt-PA ) use for acute ischemic stroke in rural underserved communities . The purpose of this study was to prospect ively assess whether telemedicine or telephone was superior for decision-making . METHODS The study design is a pooled analysis of two identically design ed r and omized controlled trials conducted in a multistate hub and spoke telestroke network setting with acute stroke syndrome patients , comparing telemedicine versus telephone-only consultations . From each trial , common data elements were pooled to assess , principally , for correctness of thrombolysis decision-making . Secondary outcomes included rt-PA use rate , 90-day functional outcome , post-thrombolysis intracranial hemorrhage , and data completeness . RESULTS Two hundred seventy-six pooled patients were evaluated . Correct thrombolysis eligibility decisions were made more often with telemedicine ( 96 % telemedicine , 83 % telephone ; odds ratio [ OR ] 4.2 ; 95 % confidence interval [ CI ] 1.69 - 10.46 ; p=0.002 ) . Intravenous rt-PA usage was 26 % ( 29 % telemedicine , 24 % telephone ; OR 1.27 ; 95 % CI 0.71 - 2.25 ; p=0.41 ) . Ninety-day outcomes were not different for Barthel Index , modified Rankin Scale , or mortality . There was no difference in post-thrombolysis intracranial hemorrhage ( 8 % telemedicine , 6 % telephone ; p>0.999 ) . CONCLUSIONS This pooled analysis supports the hypothesis that stroke telemedicine consultations , compared with telephone-only , result in more accurate decision-making . Together with high rt-PA utilization rate , low post-rt-PA intracranial hemorrhage rate , and acceptable patient outcome , the results confirm that telemedicine is a viable consultative tool for acute stroke . The replication of the hub and spoke network infrastructure supports the generalizability of telemedicine when used in broader setting We conducted a pilot telerehabilitation study with post-stroke patients with arm motor impairment . We compared the degree of satisfaction of patients undergoing a virtual reality ( VR ) therapy programme at home ( Tele-VR group ) to satisfaction experienced by those undergoing the same VR therapy in a hospital setting ( VR-group ) . The rehabilitation equipment used a 3D motion tracking system to create a virtual environment in which the patient 's movement was represented . In tele-therapy , the patient equipment was installed in their homes , connected to the hospital by four ISDN lines at a total b and width of 512 kbit/s . Rehabilitation data were transmitted via one line and videoconferencing via the other three . Ten patients with mild to intermediate arm motor impairment due to an ischaemic stroke , were r and omized into VR or Tele-VR groups . A question naire was used at the end of treatment to measure each patient 's degree of satisfaction . Tele-VR treated patients showed median values equal to or higher than the VR group patients in all 12 items investigated , except one . In motor performance , the Tele-VR group improved significantly ( P ≤ 0.05 ) , while the VR group showed no significant change . Patients assigned to the Tele-VR group were able to engage in therapy at home and the videoconferencing system ensured a good relationship between the patient and the physical therapist whose physical proximity was not required Background and Purpose — Telemedicine techniques can be used to address the rural – metropolitan disparity in acute stroke care . The Stroke Team Remote Evaluation Using a Digital Observation Camera ( STRokE DOC ) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use , improved data collection , low risk of complications , low technical complications , and favorable assessment times . The main objective of the STRokE DOC Arizona TIME ( The Initial Mayo Clinic Experience ) trial was to determine the feasibility of establishing , de novo , a single-hub , multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol . Methods — Methods included prospect i ve , single-hub , 2-spoke , r and omized , blinded , controlled trial of a 2-way , site-independent , audiovisual telemedicine system design ed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis . The primary outcome measure was whether the decision to give thrombolysis was correct . Secondary outcomes were rate of thrombolytic use , 90-day functional outcomes , incidence of intracerebral hemorrhages , and technical observations . Results — From December 2007 to October 2008 , 54 patients were assessed , 27 of whom were r and omized to each arm . Mean National Institutes of Health Stroke Scale score at presentation was 7.3 ( SD 6.2 ) points . No consultations were aborted ; however , technical problems ( 74 % ) were prevalent in the telemedicine arm . Overall , the correct treatment decision was established in 87 % of the consultations . Both modalities , telephone ( 89 % correct ) and telemedicine ( 85 % correct ) , performed well . Intravenous thrombolytic treatment was used in 30 % of the telemedicine and telephone consultations . Good functional outcomes at 90 days were not significantly different . There were no statistically significant differences in mortality ( 4 % in telemedicine and 11 % in telephone ) or rates of intracerebral hemorrhage ( 4 % in telemedicine and 0 % in telephone ) . Conclusions — It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub , multispoke rural hospital telestroke research network in Arizona . The trial was not design ed to have sufficient power to detect a difference between the 2 consultative modes : telemedicine and telephone-only . Whether by telemedicine or telephone consultative modalities , there were appropriate treatment decisions , high rates of thrombolysis use , improved data collection , low rates of intracerebral hemorrhage , and equally favorable time requirements . The learning curve was steep for the hub and spoke personnel of the new telestroke network , as reflected by frequent technical problems . Overall , the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise Background and Purpose — Despite Food and Drug Administration approval of tissue-type plasminogen activator for stroke , obstacles in the US healthcare system prevent its widespread use . The Remote Evaluation for Acute Ischemic Stroke ( REACH ) program was developed to address these issues in rural setting s. A key component of stroke assessment in the REACH system is the National Institutes of Health Stroke Scale ( NIHSS ) evaluation . We sought to determine whether , using the REACH system , NIHSS values of bedside and remote evaluators would correspond . Methods — Twenty patients were recruited . On obtaining consent , a neurologist performed a bedside NIHSS evaluation on each patient . Within 1 hour , using any broadb and -connected workstation — either office or home personal computer and a l and line phone to speak with the patient — a second neurologist remotely evaluated the patient through the REACH system . Paired t tests and Pearson correlation coefficients were used to examine NIHSS reliability performed bedside and remotely . Results — NIHSS ranged from 1 to 24 . Correlations between bedside and remote locations ( r = 0.9552 , P = 0.0001 ) were very strong , and t tests indicate that the means were not different . Conclusions — The NIHSS can be reliably performed over the REACH system . This supports our endeavor to bring stroke expertise to rural community hospitals We conducted a r and omized controlled multicentre trial to investigate the feasibility of a telerehabilitation intervention for arm/h and function ( the Home Care Activity Desk [ HCAD ] training ) in a home setting . Usual care was compared to HCAD training . The hypothesis was that the clinical outcomes of the HCAD intervention would be at least the same as those measured after a period of usual care for patients with stroke , traumatic brain injury ( TBI ) and multiple sclerosis ( MS ) with respect to their arm/h and function . Eighty-one patients with affected arm/h and function result ing from either stroke , MS or TBI were recruited in Italy , Spain and Belgium ; 11 were lost during follow-up ( 14 % ) . The outcome measures were the Action Research Arm Test ( ARAT ) and the Nine Hole Peg Test ( NHPT ) . There were no significant differences between the two groups on the outcome measures ( ARAT and NHPT ) ; in both groups , patients maintained or even improved their arm/h and function . The HCAD training was found to be as feasible as usual care in terms of clinical outcomes , and both therapists and patients were satisfied with the HCAD intervention . A telerehabilitation intervention using HCAD may increase the efficiency of care BACKGROUND To increase the effective use of thrombolytics for acute stroke , the expertise of vascular neurologists must be disseminated more widely . We prospect ively assessed whether telemedicine ( real-time , two-way audio and video , and digital imaging and communications in medicine [ DICOM ] interpretation ) or telephone was superior for decision making in acute telemedicine consultations . METHODS From January , 2004 , to August , 2007 , patients older than 18 years who presented with acute stroke symptoms at one of four remote spoke sites were r and omly assigned , through a web-based , permuted blocks system , to telemedicine or telephone consultation to assess their suitability for treatment with thrombolytics , on the basis of st and ard criteria . The primary outcome measure was whether the decision to give thrombolytic treatment was correct , as determined by central adjudication . Secondary outcomes were the rate of thrombolytic use , 90-day functional outcomes ( Barthel index [ BI ] and modified Rankin scale [ mRS ] ) , the incidence of intracerebral haemorrhages , and technical observations . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00283868 . FINDINGS 234 patients were assessed prospect ively . 111 patients were r and omised to telemedicine , and 111 patients were r and omised to telephone consultation ; 207 completed the study . Mean National Institutes of Health stroke scale score at presentation was 9.5 ( SD 8.1 ) points ( 11.4 [ 8.7 ] points in the telemedicine group versus 7.7 [ 7.0 ] points in the telephone group ; p=0.002 ) . One telemedicine consultation was aborted for technical reasons , although it was included in the analyses . Correct treatment decisions were made more often in the telemedicine group than in the telephone group ( 108 [ 98 % ] vs 91 [ 82 % ] , odds ratio [ OR ] 10.9 , 95 % CI 2.7 - 44.6 ; p=0.0009 ) . Intravenous thrombolytics were used at an overall rate of 25 % ( 31 [ 28 % ] telemedicine vs 25 [ 23 % ] telephone , 1.3 , 0.7 - 2.5 ; p=0.43 ) . 90-day functional outcomes were not different for BI ( 95 - 100 ) ( 0.6 , 0.4 - 1.1 ; p=0.13 ) or for mRS score ( 0.6 , 0.3 - 1.1 ; p=0.09 ) . There was no difference in mortality ( 1.6 , 0.8 - 3.4 ; p=0.27 ) or rates of intracerebral haemorrhage after treatment with thrombolytics ( 2 [ 7 % ] telemedicine vs 2 [ 8 % ] telephone , 0.8 , 0.1 - 6.3 ; p=1.0 ) . However , there were more incomplete data in the telephone group than in the telemedicine group ( 12%vs 3 % , 0.2 , 0.1 - 0.3 ; p=0.0001 ) . INTERPRETATION The authors of this trial report that stroke telemedicine consultations result in more accurate decision making compared with telephone consultations and can serve as a model for the effectiveness of telemedicine in other medical specialties . The more appropriate decisions , high rates of thrombolysis use , improved data collection , low rate of intracerebral haemorrhage , low technical complications , and favourable time requirements all support the efficacy of telemedicine for making treatment decisions , and might enable more practitioners to use this medium in daily stroke care |
2,141 | 28,084,563 | The cyclophosphamide group had a significantly higher risk of leukopenia , whereas the tacrolimus group had significantly higher rates of tremor . | Objective The objective of this systematic review was to compare the efficacy and safety of tacrolimus with cyclophosphamide in primary membranous nephropathy ( PMN ) patients . | Although idiopathic membranous nephropathy ( IMN ) is the most common cause of adult-onset nephrotic syndrome , the management of IMN remains controversial . The aim of this prospect i ve study was to compare the efficacy and drug safety of tacrolimus with that of cyclophosphamide ( CTX ; control group ) in IMN patients receiving corticosteroid therapy . A total of 100 IMN patients with nephrotic syndrome were r and omly assigned to receive a combination of corticosteroid therapy and either CTX or tacrolimus . During a follow-up period of at least 18 months , the remission rate after 2 months in the tacrolimus group was 65.1 % , which was higher than that of the CTX group ( 44.2 % ) ( p = 0.02 ) . The mean time to partial or complete remission was 2.20 months in the tacrolimus group and 3.92 months in the CTX group ( p < 0.001 ) . We also found significantly greater improvements in the serum albumin levels in the tacrolimus group compared with the CTX group at the 2-month ( p = 0.003 ) and 3-month time points ( p = 0.01 ) . The serum creatinine levels remained stable in both groups . Although remission was quicker and more common in the tacrolimus group ( compared with the CTX group ) before 3 months , there was no superiority of tacrolimus after 6 months . Glucose intolerance , urinary tract infections , and pneumonia were the major side effects observed in this study . All of the side effects were mild and controlled , and there were fewer side effects in the tacrolimus group compared with the CTX group , indicating a better treatment tolerance in the tacrolimus group BACKGROUND Evidence regarding the optimal dose of tacrolimus ( TAC ) in treatment of idiopathic membranous nephropathy ( IMN ) remains inconclusive . The objective of this study was to evaluate the efficacy and safety of low-dose TAC combined with prednisone for patients with IMN . METHODS We conducted a r and omized prospect i ve cohort study in IMN patients : 28 patients received oral TAC ( target whole blood concentration of 2 - 4 ng/mL ) plus prednisone for 12 months , and 28 patients received prednisone combined with intravenous cyclophosphamide ( CYC ) ( 750 mg/m2 body surface ) once every 4 weeks for 24 weeks . RESULTS Of the 56 patients who completed the 12-month treatment , complete remission ( CR ) occurred in 8 ( 28.6 % ) of the CYC group and 18 ( 64.3 % ) of the TAC group ; partial remission ( PR ) occurred in 10 ( 35.7 % ) of the CYC group and 7 ( 25.0 % ) of the TAC group . The probability of remission ( either CR or PR ) was higher in the TAC group than in the CYC group ( p = 0.0439 , by log-rank test ) . Furthermore , a significantly greater improvement in proteinuria and serum albumin levels was observed in the TAC group compared with the CYC group . Patients treated with TAC can often show a rapid increase in their serum albumin levels before any obvious reduction of urinary protein excretion . Side effects were mild and transitory in both groups . CONCLUSION The results demonstrated that the combined therapy of low-dose TAC and prednisone is an effective and safe therapeutic method for Chinese adults with IMN . Low-dose TAC accompanied by prednisone is enough to induce remission in the majority of patients with IMN BACKGROUND Calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation , but the optimum initial immunosuppression regimen is not known . The aim of our study was to compare tacrolimus with microemulsified ciclosporin , in a regimen with st and ardised concomitant immunosuppressive therapy . METHODS In all liver transplant centres in the UK and Republic of Irel and , 606 patients undergoing a first orthotopic liver transplantation were r and omly assigned open-label tacrolimus or microemulsified ciclosporin . Primary outcome was the combined frequency ( whichever occurred first ) of death , retransplantation , or treatment failure for immunological reasons , analysed by intention to treat . FINDINGS 96 % of patients received the treatment allocated to them . The primary outcome was reached in 62 ( 21 % ) of 301 patients in the tacrolimus group versus 99 ( 32 % ) of 305 allocated microemulsified ciclosporin ( relative risk 0.63 [ 95 % CI 0.48 - 0.84 ] , p=0.001 ; time-to-event analysis log-rank test p=0.002 ) : deaths ( 50 [ 17 % ] vs 72 [ 24 % ] ) ; retransplantations ( 11 [ 4 % ] vs 31 [ 10 % ] ) treatment failure for immunological reasons ( 6 [ 2 % ] vs 12 [ 4 % ] ) . The relative risk for the composite outcome was in favour of tacrolimus . The main causes of death in both trial groups were sepsis and multiple organ failure ( 31 [ 10 % ] vs 30 [ 10 % ] ) , and the main cause for retransplantation was hepatic artery thrombosis ( 6 [ 2 % ] vs 17 [ 6 % ] ) . Renal dysfunction and the need for antihypertensive therapy were much the same in both groups . Tacrolimus was more diabetogenic . INTERPRETATION Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation . Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft BACKGROUND AND OBJECTIVES Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy . However , use of cyclophosphamide is associated with cancer . The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated , and the cancer risk associated with cyclophosphamide use was estimated . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Patients who attended the clinic were included prospect ively from 1995 on . A crude incidence ratio for the occurrence of malignancy was calculated . Incidence ratios were subsequently st and ardized to potential confounders . Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment . Finally , Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose-response relationship between cyclophosphamide and cancer . RESULTS Data were available for 272 patients ; the mean age was 51 years , and 70 % of the patients were men . Median follow-up was 6.0 years ( interquartile range=3.6 - 9.5 ) , and 127 patients were treated with cyclophosphamide . Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 person-years in patients who did not receive cyclophosphamide , result ing in crude and adjusted incidence ratios of 4.6 ( 95 % confidence interval , 1.5 to 18.8 ) and 3.2 ( 95 % confidence interval , 1.0 to 9.5 ) , respectively . CONCLUSION Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk . For the average patient , this finding translates into an increase in annual risk from approximately 0.3 % to 1.0 % . The increased risk of malignancy must be balanced against the improved renal survival BACKGROUND To examine whether tacrolimus is more effective and safe than cyclosporine ( CsA ) in inducing remission in patients with steroid-resistant nephrotic syndrome ( SRNS ) . STUDY DESIGN R and omized controlled trial , nonblind , parallel group . SETTING S & PARTICIPANTS Tertiary-care hospital ; 41 consecutive patients with idiopathic SRNS , estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2 ) , and histological characteristics showing minimal change disease , focal segmental glomerulosclerosis , or mesangioproliferative glomerulonephritis were r and omly assigned to treatment with tacrolimus ( n = 21 ) or CsA ( n = 20 ) . INTERVENTION Tacrolimus ( 0.1 to 0.2 mg/kg/d ) or CsA ( 5 to 6 mg/kg/d ) for 1 year ; cotreatment with alternate-day prednisolone and enalapril . OUTCOMES Patients achieving complete remission ( urinary protein-creatinine ratio < 0.2 g/g and serum albumin > or = 2.5 g/dL ) or partial remission ( urinary protein-creatinine ratio , 0.2 to 2 g/g , and serum albumin > or = 2.5 g/dL ) at 6 and 12 months ; time to remission ; proportion with relapses ; side effects . RESULTS No patient was lost to follow-up . After 6 months of therapy , remission occurred in 18 ( 85.7 % ) and 16 patients ( 80 % ) treated with tacrolimus and CsA , respectively ( relative risk [ RR ] , 1.07 ; 95 % confidence interval [ CI ] , 0.81 to 1.41 ) . Rates of remission at 12 months were also similar ( RR , 1.14 ; 95 % CI , 0.84 to 1.55 ) . The proportion of patients who experienced relapse was significantly greater in those receiving CsA compared with tacrolimus ( RR , 4.5 ; 95 % CI , 1.1 to 18.2 ; P = 0.01 ) . The decrease in blood cholesterol levels was greater with tacrolimus compared with CsA ( difference in mean values , 45.1 mg/dL ; 95 % CI , 19.1 to 71.2 ) . Persistent nephrotoxicity necessitating stoppage of medicine was seen in 4.7 % and 10 % patients , respectively . Cosmetic side effects ( hypertrichosis and gum hypertrophy ) were significantly more frequent in CsA-treated patients ( P < 0.001 ) . LIMITATIONS Single-center study , small sample size , and short duration of follow-up . CONCLUSIONS Tacrolimus or CsA in combination with low-dose steroids show similar efficacy in inducing remission in patients with SRNS . Therapy with tacrolimus is a promising alternative to CsA in view of the lower risk of relapses and lack of cosmetic side effects BACKGROUND Membranous nephropathy is a common cause of nephrotic syndrome ( NS ) in adults . Its treatment is still under debate . METHODS We report our experience in a pilot study using initially low doses of steroids and tacrolimus ( Tac ) . After 3 months of treatment , mycophenolate mofetil ( MMF ) was added if the proteinuria was higher than 1 g/day . RESULTS In accordance with this st and ard , 21 patients entered the study . A proteinuria level lower than 1 g/day was reached at month 3 of therapy with steroids and Tac in 11 patients . These patients continued this treatment for 12 months . MMF was added in nine cases after the third month and triple therapy was maintained for 12 more months . Two patients were withdrawn because of side effects . At the end of the treatment , remission of the NS was present in 15 out of all the patients ( 71.4 % ) . Remission of the NS was complete in eight ( 53.3 % ) patients and partial in seven ( 46.7 % ) others . The remaining four patients did not respond . There were no significant changes in renal function . At a mean time of 23.1 months after treatment was discontinued , 11 ( 73.3 % ) patients had relapsed . CONCLUSIONS In this trial , treatment with tacrolimus showed a good efficacy but a high relapse rate when it was discontinued Membranous nephropathy is a common cause of nephrotic syndrome in adults . Although some patients with membranous nephropathy achieve a spontaneous remission , renal function continues to deteriorate in others . We conducted a prospect i ve r and omized trial evaluating monotherapy with tacrolimus to achieve complete or partial remission in patients with biopsy-proven membranous nephropathy . Twenty-five patients received tacrolimus ( 0.05 mg/kg/day ) over 12 months with a 6-month taper , whereas 23 patients were in the control group . The probability of remission in the treatment group was 58 , 82 , and 94 % after 6 , 12 , and 18 months but only 10 , 24 , and 35 % , respectively in the control group . The decrease in proteinuria was significantly greater in the treatment group . Notably , six patients in the control group and only one in the treatment group reached the secondary end point of a 50 % increase in their serum creatinine . No patient in the tacrolimus group showed a relapse during the taper period . Nephrotic syndrome reappeared in almost half of the patients who were in remission by the 18th month after tacrolimus withdrawal . We conclude that tacrolimus is a very useful therapeutic option for patients with membranous nephropathy and preserved renal function . The majority of patients experienced remission with a significant reduction in the risk for deteriorating renal function BACKGROUND Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy . The course of the disorder is often benign , and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks . We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy . METHODS We prospect ively studied 100 consecutive patients ( 68 men and 32 women ; mean [ + /- SD ] age , 51 + /- 17 years ) with biopsy-proved idiopathic membranous nephropathy . The patients received diuretic or antihypertensive drugs as needed , but no glucocorticoid or immunosuppressive drugs . We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months . RESULTS Twenty-four ( 65 percent ) of the 37 patients followed for at least five years had complete or partial remission of proteinuria ; in 6 others ( 16 percent ) , end-stage renal disease developed , and they required dialysis . As calculated by the Kaplan-Meier method , the estimated probability ( + /- the st and ard error of the estimate ) of retaining adequate kidney function was 88 + /- 5 percent after five years and 73 + /- 7 percent after eight years . The prognosis was poorer in men and in patients over 50 years of age , but not in patients with the nephrotic syndrome , hypertension , or hypercholesterolemia . CONCLUSIONS Most untreated patients with idiopathic membranous nephropathy maintain renal function for prolonged periods and are likely to have spontaneous remission . These results do not support the use of glucocorticoids and immunosuppressive drugs in patients with idiopathic membranous nephropathy Objective : Tacrolimus has been used for idiopathic membranous nephropathy ( IMN ) therapy , but most patients who achieved remission showed a high relapse rate when tacrolimus was withdrawn after 6 - 12 months of therapy . We proposed that a prolonged therapeutic course should help reduce the relapse rate . Methods : A total of 42 patients with nephrotic syndrome caused by IMN were r and omly divided into short-term ( n = 20 ) and long-term ( n = 22 ) groups . All patients received initial treatment with tacrolimus and prednisone for 6 months , and afterward only the long-term patient group was tapered with low-dose tacrolimus until 24 months . Results : Over 85 % of the patients achieved proteinuria reduction , serum albumin improvement and serum lipid recovery ; the probability of remission in both groups was over 80 % at 6 months . The remission rate was steady at over 80 % after 12 and 24 months in the long-term group , but only 50 and 45 % , respectively , in the short-term group . Nine patients ( 45 % ) relapsed in the short-term group after tacrolimus withdrawal , while not a single patient suffered recurrence in the long-term group . The concentration of tacrolimus remained similar between the two groups at 5 - 8 ng/ml during the initial 6 months , and was significantly decreased at 12 months compared to 6 months ( p < 0.05 ) , along with reduction of oral administration in the long-term group . Conclusion : Combined therapy of tacrolimus with prednisone can relieve IMN significantly ; prolonged tacrolimus treatment at a low blood concentration can alleviate the illness persistently , with a low recurrence rate and gratifying safety BACKGROUND / PURPOSE Immunosuppressive therapy plays an important role in patients with high-risk idiopathic membranous nephropathy ( IMN ) , but the therapeutic modality is still controversial . METHODS Corticosteroid combined with oral tacrolimus ( TAC , target trough blood concentration of 4 - 8 ng/mL ) , intravenous cyclophosphamide ( CYC , 750 mg/m(2)/mo , or oral mycophenolate mofetil ( MMF , 1.5 - 2.0 g/d ) were r and omly administered for 9 months to 90 patients with IMN proved with renal biopsy with severe proteinuria ( > 8 g/d ) . RESULTS Eighty-six of the 90 patients completed the study . The total remission ( TR ) rates in the TAC group were significantly higher than those in the CYC group at 1 and 2 months ( p < 0.01 ) and the MMF group at 1 - 4 months ( p < 0.01 ) . The TR rates were 83.3 % , 73.3 % , and 70.0 % in the TAC , CYC , and MMF groups at 9 months ( p = 0.457 ) , and there were no significant differences between the three groups from 5 to 9 months . Furthermore , TAC reduced proteinuria and ameliorated hypoalbuminemia more quickly and effectively than CYC and MMF . We observed no severe adverse events in the three groups . CONCLUSION Tacrolimus combined with corticosteroid had tolerable adverse effects and induced the remission of IMN more effectively and more rapidly . This is the first prospect i ve r and omized cohort study to compare three different therapies in patients at high risk for IMN . It provides strong evidence for choosing optimal treatment for patients with IMN . The long-term efficacy of this treatment strategy should be investigated further in future studies We compared efficacy and safety of tacrolimus (Tac)‐based vs. cyclosporine ( CyA ) microemulsion‐based immunosuppression in combination with azathioprine ( Aza ) and corticosteroids in heart transplant recipients . During antibody induction , patients were r and omized ( 1:1 ) to oral treatment with Tac or CyA. Episodes of acute rejection were assessed by protocol biopsies , which underwent local and blinded central evaluation . The full analysis set comprised 157 patients per group . Patient/graft survival was 92.9 % for Tac and 89.8 % for CyA at 18 months . The primary end point , incidence of first biopsy proven acute rejection ( BPAR ) of grade ≥ 1B at month 6 , was 54.0 % for Tac vs. 66.4 % for CyA ( p = 0.029 ) according to central assessment . Also , incidence of first BPAR of grade ≥ 3A at month 6 was significantly lower for Tac vs. CyA ; 28.0 % vs. 42.0 % , respectively ( p = 0.013 ) . Significant differences ( p < 0.05 ) emerged between groups for these clinical ly relevant adverse events : new‐onset diabetes mellitus ( 20.3 % vs. 10.5 % ) ; post‐transplant arterial hypertension ( 65.6 % vs. 77.7 % ) ; and dyslipidemia ( 28.7 % vs. 40.1 % ) for Tac vs. CyA , respectively . Incidence and pattern of infections over 18 months were comparable between groups , as was renal function . Primary use of Tac during antibody induction result ed in superior prevention of acute rejection without an associated increase in infections AIM There have been very few studies comparing cyclophosphamide ( CTX ) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy ( NIST ) resistant idiopathic membranous nephropathy ( IMN ) . The present study was aim ed at comparing the efficacy and safety of tacrolimus (TAC)/steroids with cyclical CTX/steroids ( Modified Ponticelli regimen ( MPR ) ) in patients with IMN . METHODS Idiopathic membranous nephropathy patients ( n = 70 ) with persistent nephrotic syndrome after at least 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally r and omized to receive TAC with oral prednisolone ( TAC * ) or MPR . Antibodies against m-type phospholipase A2 receptor ( PLA2R Ab ) were tested for at baseline and , at 6 and 12 months after the start of therapy . The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups . RESULTS Intention-to-treat analysis showed that remissions at the end of 6 ( 74 % with TAC * vs. 60 % with MPR ; P = 0.30 ) and 12 months ( 71 % with TAC * vs. 77 % with MPR ; P = 0.78 ) were comparable . PLA2R Ab titres at 6/12 months correlated with urine protein ( r 0.54/0.58 ) and serum albumin ( r -0.49/-0.53 ) at the end of therapy . Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity . CONCLUSION In NIST refractory IMN , both TAC * and MPR are comparable , but with different adverse effect profile . PLA2 R Ab has a very good association with proteinuria , and should be regularly monitored on clinical follow-up BACKGROUND Early initiation of therapy is warranted for patients with idiopathic membranous nephropathy ( IMN ) who have severe proteinuria . Therapy with tacrolimus ( TAC ) or intravenous cyclophosphamide ( CYC ) may be an option in treating such patients . METHODS This prospect i ve cohort study included patients with IMN whose daily proteinuria was greater than 6.0 g with 3 - 6 months observation of nonimmunosuppressive therapy . One cohort received prednisone combined with oral TAC ( target trough blood level of 4 - 8 ng/mL ) for 24 weeks . The other cohort received prednisone combined with intravenous CYC ( 750 mg/m2 body surface ) every 2 weeks for the first 8 weeks and then once per 4 weeks for the next 16 weeks . RESULTS Thirty patients met criteria for enrollment , and 25 patients completed therapy . The results of the 24-week therapeutic period were complete remission ( CR ) 4 patients ( 30.8 % ) on CYC and 8 patients ( 66.7 % ) on TAC ; partial remission ( PR ) 7 patients ( 53.8 % ) on CYC and 3 patients ( 25 % ) on TAC ; no response 2 patients ( 15.4 % ) on CYC and 1 patient ( 8.3 % ) on TAC . The percentages of remission ( either PR or CR ) by 4 and 8 weeks were significantly higher in TAC group than in CYC group ( p < or=0.05 ) . The probability of CR was significantly higher in the TAC group than in the CYC group ( p=0.018 , by log-rank test ) . CONCLUSION Earlier initiation of therapy with TAC or intravenous CYC ( combined steroid ) for 24 weeks was useful for Chinese adults with IMN in inducing remission of severe proteinuria , and quicker remission was seen in TAC therapy Background : Idiopathic membranous nephropathy ( IMN ) , a common cause of nephrotic syndrome in adults , is usually treated with corticosteroids in combination with cyclophosphamide or cyclosporine . A recent placebo-controlled study suggested that tacrolimus monotherapy was effective in IMN . However , the effectiveness of tacrolimus versus classic regimen and its potential nephrotoxicity remain inconclusive . This study evaluated the efficacy and safety of tacrolimus plus prednisone in patients with nephrotic IMN . Methods : Seventy-three patients with nephrotic IMN were recruited in this multicenter r and omized controlled trial , 39 receiving tacrolimus and prednisone , while 34 receiving cyclophosphamide and prednisone . Tacrolimus was given at 0.1 mg/kg/d initially and adjusted to a blood trough level at 5 to 10 ng/mL for 6 months and then reduced to 2 to 5 ng/mL in the subsequent 3 months . Results : Intention-to-treat analysis suggested that the remission rate at the end of the sixth month was significantly higher in tacrolimus group than that in cyclophosphamide group ( 85 % versus 65 % , P < 0.05 ) . The decrease of proteinuria was significantly greater in tacrolimus group . At the end of the 12th month , the remission rates were comparable between these 2 groups . Patients treated with tacrolimus were more likely to develop glucose intolerance ( or diabetes mellitus ) , infection , and hypertension . No obvious nephrotoxicity of calcineurin inhibitor was found in repeat renal biopsy . Conclusions : Tacrolimus plus corticosteroids is an alternative therapeutic regimen for nephrotic IMN . The short-term efficacy might be better than cyclophosphamide plus prednisone |
2,142 | 27,349,212 | Left ventricular ejection fraction ( LVEF ) was improved in the majority of trials after therapy .
Cell delivery combined with coronary artery bypass grafting was associated with the greatest improvement in LVEF .
Left ventricular end-systolic volume ( or diameter ) , New York Heart Association functional classification , quality of life , and exercise capacity were also improved in most studies after cell therapy .
Most ICM trials demonstrated a significant improvement in perfusion defects , infa rct size , and myocardial viability .
Stem cells are a promising therapeutic modality for patients with heart failure due to ICM or NICM . | The benefits of stem cell therapy for patients with chronic symptomatic systolic heart failure due to ischemic and nonischemic cardiomyopathy ( ICM and NICM , respectively ) are unclear .
We performed a systematic review of major published and ongoing trials of stem cell therapy for systolic heart failure and compared measured clinical outcomes for both types of cardiomyopathy . | Background —This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility . Methods and Results —Twenty-one patients were enrolled in this prospect i ve , nonr and omized , open-label study ( first 14 patients , treatment ; last 7 patients , control ) . Baseline evaluations included complete clinical and laboratory evaluations , exercise stress ( ramp treadmill ) , 2D Doppler echocardiogram , single-photon emission computed tomography perfusion scan , and 24-hour Holter monitoring . Bone marrow mononuclear cells were harvested , isolated , washed , and resuspended in saline for injection by NOGA catheter ( 15 injections of 0.2 cc ) . Electromechanical mapping was used to identify viable myocardium ( unipolar voltage ≥6.9 mV ) for treatment . Treated and control patients underwent 2-month noninvasive follow-up , and treated patients alone underwent a 4-month invasive follow-up according to st and ard protocol s and with the same procedures used as at baseline . Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups ; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up , being relatively higher in control patients . At 2 months , there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups ( P = 0.02 ) on quantitative single-photon emission computed tomography analysis . At 4 months , there was improvement in ejection fraction from a baseline of 20 % to 29 % ( P = 0.003 ) and a reduction in end-systolic volume ( P = 0.03 ) in the treated patients . Electromechanical mapping revealed significant mechanical improvement of the injected segments ( P < 0.0005 ) at 4 months after treatment . Conclusions —Thus , the present study demonstrates the relative safety of intramyocardial injections of bone marrow – derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function Rationale : Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration . Objective : To evaluate the safety and efficacy of ixmyelocel-T in 2 prospect i ve r and omized phase 2A Trials administered via minithoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy ( DCM ) stratified by ischemic or nonischemic status . Methods and Results : In IMPACT-DCM , patients were r and omized to either ixmyelocel-T or st and ard-of-care control in a 3:1 ratio ( n=39 ) ; ixmyelocel-T was administered intramyocardially via minithoracotomy . In Catheter-DCM , patients were r and omized to either ixmyelocel-T or st and ard of care control in a 2:1 ratio ( n=22 ) ; ixmyelocel-T was administered intramyocardially using the NOGA Myostar catheter . Only patients r and omized to ixmyelocel-T underwent bone marrow aspiration and injections . In the 2 studies , a total of 61 patients were r and omized , and 59 were treated or received st and ard of care . Fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up when compared with control patients . A similar benefit was not seen in the nonischemic patients . Heart failure exacerbation was the most common major adverse cardiovascular event . Ixmyelocel-T treatment was associated with improved New York Heart Association class , 6-minute walk distance , and Minnesota Living with Heart Failure Question naire scores in the ischemic population relative to control ; a similar trend was not observed in the nonischemic population . Conclusions : Intramyocardial injection with ixmyelocel-T reduces major adverse cardiovascular event and improves symptoms in patients with ischemic DCM but not in patients with nonischemic DCM AIMS Despite accumulated evidence that intracoronary bone marrow cell ( BMC ) therapy may be beneficial in acute myocardial infa rct ion , there are only limited data available on the effectiveness of BMC 's in chronic heart failure . The aim of this study was to quantitatively investigate ventricular haemodynamics , geometry , and contractility as well as the long-term clinical outcome of BMC treated patients with reduced left ventricular ejection fraction ( LVEF ) due to chronic ischaemic cardiomyopathy . METHODS AND RESULTS Patients with chronic heart failure ( n = 391 LVEF < or=35 % ) due to ischaemic cardiomyopathy were enrolled in the present study . Of these , 191 patients ( mean NYHA class 3.22 ) underwent intracoronary BMC therapy . The control group ( mean NYHA class 3.06 ) consisted of 200 patients with comparable LVEF . Assessment s of haemodynamics at rest and exercise , quantitative ventriculography , spiroergometry , 24 h Holter ECG , late potentials , and heart rate variability were analysed . Over 3 months to 5 years after intracoronary BMC therapy there was a significant improvement in haemodynamics ( e.g. LVEF , cardiac index ) , exercise capacity , oxygen uptake , and LV contractility . Importantly , there was a significant decrease in long-term mortality in the BMC treated patients compared with the control group . CONCLUSION Intracoronary BMC therapy improves ventricular performance , quality of life and survival in patients with heart failure . These effects were present when BMC were administered in addition to st and ard therapeutic regimes . No side effects were observed OBJECTIVES This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure . BACKGROUND In pre- clinical heart failure models , cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling . METHODS The C-CURE ( Cardiopoietic stem Cell therapy in heart failURE ) trial , a prospect i ve , multicenter , r and omized trial , was conducted in patients with heart failure of ischemic origin who received st and ard of care or st and ard of care plus lineage-specified stem cells . In the cell therapy arm , bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail . Derived cardiopoietic stem cells , meeting release criteria under Good Manufacturing Practice , were delivered by endomyocardial injections guided by left ventricular electromechanical mapping . Data acquisition and analysis were performed in blinded fashion . The primary endpoint was feasibility/safety at 2-year follow-up . Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy . RESULTS Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75 % and delivery without complications in 100 % of cases . There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy . Left ventricular ejection fraction was improved by cell therapy ( from 27.5 ± 1.0 % to 34.5 ± 1.1 % ) versus st and ard of care alone ( from 27.8 ± 2.0 % to 28.0 ± 1.8 % , p < 0.0001 ) and was associated with a reduction in left ventricular end-systolic volume ( -24.8 ± 3.0 ml vs. -8.8 ± 3.9 ml , p < 0.001 ) . Cell therapy also improved the 6-min walk distance ( + 62 ± 18 m vs. -15 ± 20 m , p < 0.01 ) and provided a superior composite clinical score encompassing cardiac parameters in t and em with New York Heart Association functional class , quality of life , physical performance , hospitalization , and event-free survival . CONCLUSIONS The C-CURE trial implements the paradigm of lineage guidance in cell therapy . Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure , meriting definitive clinical evaluation . ( C-Cure Clinical Trial ; NCT00810238 ) BACKGROUND Autologous adult stem cell transplantation has been touted as the latest tool in regenerative medical therapy . Its potential for use in cardiovascular disease has only recently been recognized . A r and omized study was conducted with a novel epicardial technique to deploy stem cells as an adjuvant to conventional revascularization therapy in patients with congestive heart failure . METHODS After institutional review board and government approval , adult autologous stem cell transplantation ( CD34 + ) was performed in patients with ischemic cardiomyopathy and an ejection fraction of less than 35 % who were scheduled for primary off-pump coronary artery bypass grafting . Preoperatively , the patients underwent echocardiography , stress thallium imaging single photon emission computed tomography , and cardiac catheterization to identify ischemic regions of the heart and to guide in the selection of stem cell injection sites . The patients were prospect ively r and omized before the operative therapy was performed . Patient follow-up was 1 , 3 , and 6 months with echocardiography , single photon emission computed tomography , and angiography . RESULTS There were 20 patients enrolled in the study . Ten patients had successful subepicardial transplantation of autologous stem cells into ischemic myocardium . The other 10 patients , the control group , only had off-pump coronary artery bypass grafting . There were 8 male and 2 female subjects in each group . The median number of grafts performed was 1 in both groups . On angiographic follow-up , all grafts were patent at 6 months . The ejection fractions of the off-pump coronary artery bypass grafting group versus the off-pump coronary artery bypass grafting plus stem cell transplantation group were as follows : preoperative , 30.7 % + /- 2.5 % versus 29.4 % + /- 3.6 % ; 1 month , 36.4 % + /- 2.6 % versus 42.1 % + /- 3.5 % ; 3 months , 36.5 % + /- 3.0 % versus 45.5 % + /- 2.2 % ; and 6 months , 37.2 % + /- 3.4 % versus 46.1 % + /- 1.9 % ( P < .001 ) . There were no perioperative arrhythmias or neurologic or ischemic myocardial events in either group . CONCLUSIONS Autologous stem cell transplantation led to significant improvement in cardiac function in patients undergoing off-pump coronary artery bypass grafting for ischemic cardiomyopathy . Further investigation is required to quantify the optimal timing and specific cellular effects of the therapy AIMS The SEISMIC study was an open-label , prospect i ve , r and omised study to assess the safety and feasibility of percutaneous myoblast implantation in heart failure patients with implanted cardioverter-defibrillators ( ICD ) . METHODS AND RESULTS Patients were r and omised 2:1 to autologous skeletal myoblast therapy vs. optimal medical treatment . The primary safety end-point was defined as the incidence of procedural and device related serious adverse events , whereas the efficacy endpoints were defined as the change in global LVEF by MUGA scan , change in NYHA classification of heart failure and in the distance achieved during a six-minute walk test ( 6MW ) at 6-month follow-up . Forty subjects were r and omised to the treatment arm ( n=26 ) , or to the control arm ( n=14 ) . There were 12 sustained arrhythmic events and one death after episodes of ventricular tachycardia ( VT ) in the treatment group and 14 events in the control group ( P = ns ) . At 6-month follow-up , 6MW distance improved by 60.3±54.1?meters in the treated group as compared to no improvement in the control group ( 0.4±185.7?meters ; P = ns ) . In the control group , 28.6 % experienced worsening of heart failure status ( 4/14 ) , while 14.3 % experienced an improvement in NYHA classification ( 2/14 ) . In the myoblast-treatment arm , one patient experienced a deterioration in NYHA classification ( 8.0 % ) , whereas five patients improved one or two classes ( 20.0 % ; P=0.06 ) . However , therapy did not improve global LVEF measured by MUGA at 6-month follow-up . CONCLUSIONS These data indicate that implantation of myoblasts in patients with HF is feasible , appears to be safe and may provide symptomatic relief , though no significant effect was detected on global LVEF Background — In an open-label blinded study , we compared intracoronary and transendocardial CD34 + cell transplantation in patients with nonischemic dilated cardiomyopathy . Methods and Results — Of the 40 patients with dilated cardiomyopathy , 20 were r and omized to receive intracoronary injection and 20 received transendocardial CD34 + cell delivery . In both groups , CD34 + cells were mobilized by filgrastim , collected via apheresis , and labeled with technetium-99 m radioisotope for single-photon emission computed tomographic imaging . In the intracoronary group , cells were injected intracoronarily in the artery supplying segments of greater perfusion defect on myocardial perfusion scintigraphy . In the transendocardial group , electroanatomic mapping was used to identify viable but dysfunctional myocardium , and transendocardial cell injections were performed . Nuclear single-photon emission computed tomographic imaging for quantification of myocardial retention was performed 18 hours thereafter . At baseline , groups did not differ in age , sex , left ventricular ejection fraction , or N-terminal pro-brain natriuretic peptide levels . The number of CD34 + cells was also comparable ( 105±31 × 106 in the transendocardial group versus 103±27 × 106 in the intracoronary group , P=0.62 ) . At 18 hours after procedure , myocardial retention was higher in the transendocardial group ( 19.2±4.8 % ) than in the intracoronary group ( 4.4±1.2 % , P<0.01 ) . At 6 months , left ventricular ejection fraction improved more in the transendocardial group ( + 8.1±4.3 % ) than in the intracoronary group ( + 4.2±2.3 % , P=0.03 ) . The same pattern was observed for the 6-minute walk test distance ( + 125±33 m in the transendocardial group versus + 86±13 m in the intracoronary group , P=0.03 ) and N-terminal pro-brain natriuretic peptide ( −628±211 versus −315±133 pg/mL , P=0.04 ) . Conclusions — In patients with dilated cardiomyopathy , transendocardial CD34 + cell transplantation is associated with higher myocardial retention rates and greater improvement in ventricular function , N-terminal pro-brain natriuretic peptide , and exercise capacity compared with intracoronary route . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01350310 Aims The REGENERATE-DCM trial is the first phase II r and omized , placebo-controlled trial aim ing to assess if granulocyte colony-stimulating factor ( G-CSF ) administration with or without adjunctive intracoronary ( IC ) delivery of autologous bone marrow-derived cells ( BMC s ) improves global left ventricular ( LV ) function in patients with dilated cardiomyopathy ( DCM ) and significant cardiac dysfunction . Methods and results Sixty patients with DCM and left ventricular ejection fraction ( LVEF ) at referral of ≤45 % , New York Heart Association ( NYHA ) classification ≥2 and no secondary cause for the cardiomyopathy were r and omized equally into four groups : peripheral placebo ( saline ) , peripheral G-CSF , peripheral G-CSF and IC serum , and peripheral G-CSF and IC BMC . All patients , except the peripheral placebo group , received 5 days of G-CSF . In the IC groups , this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6 . The primary endpoint was LVEF change from baseline to 3 months , determined by advanced cardiac imaging . At 3 months , peripheral G-CSF combined with IC BMC therapy was associated with a 5.37 % point increase in LVEF ( 38.30 % ± 12.97 from 32.93 % ± 16.46 P = 0.0138 ) , which was maintained to 1 year . This was associated with a decrease in NYHA classification , reduced NT-pro BNP , and improved exercise capacity and quality of life . No significant change in LVEF was seen in the remaining treatment groups . Conclusion This is the first r and omized , placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function , symptoms , and biochemical parameters in patients with DCM RATIONALE Allogeneic mesenchymal precursor cells ( MPCs ) have been effective in large animal models of ischemic and nonischemic heart failure ( HF ) . OBJECTIVE To evaluate the feasibility and safety of 3 doses ( 25 , 75 , or 150 million cells ) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial . METHODS AND RESULTS We sequentially allocated 60 patients to a dosing cohort ( 20 per dose group ) and r and omized them to transendocardial MPC injections ( n=15 ) or mock procedures ( n=5 ) . The primary objective was safety , including antibody testing . Secondary efficacy end points included major adverse cardiac events ( MACE ; cardiac death , myocardial infa rct ion , or revascularization ) , left ventricular imaging , and other clinical -event surrogates . Safety and MACE were evaluated for up to 3 years . MPC injections were feasible and safe . Adverse events were similar across groups . No clinical ly symptomatic immune responses were noted . MACE was seen in 15 patients : 10 of 45 ( 22 % ) MPC-treated and 5 of 15 ( 33 % ) control patients . We found no differences between MPC-treated and control patients in survival probability , MACE-free probability , and all-cause mortality . We conducted a post hoc analysis of HF-related MACE ( HF hospitalization , successfully resuscitated cardiac death , or cardiac death ) and events were significantly reduced in the 150 million MPC group ( 0/15 ) versus control ( 5/15 ; 33 % ) , 25 million MPC group ( 3/15 ; 20 % ) , and 75 million MPC group ( 6/15 ; 40 % ) ; the 150 million MPC group differed significantly from all groups according to Kaplan-Meier statistics > 3 years ( P=0.025 for 150 million MPC group versus control ) . CONCLUSIONS Transendocardial injections of allogeneic MPCs were feasible and safe in chronic HF patients . High-dose allogeneic MPCs may provide benefits in this population BACKGROUND Ixmyelocel-T is an exp and ed , multicellular therapy produced from a patient 's own bone marrow by selectively exp and ing two key types of bone marrow mononuclear cells : CD90 + mesenchymal stem cells and CD45 + CD14 + auto-fluorescent+ activated macrophages . Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical , functional , symptomatic , and quality -of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy . We aim ed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions . METHODS In this r and omised , double-blind , placebo-controlled phase 2B trial ( ixCELL-DCM ) , patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy , who had left ventricular ejection fraction 35 % or less , an automatic implantable cardioverter defibrillator , and who were ineligible for revascularisation procedures were r and omly assigned ( 1:1 ) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months . R and omisation was done through an interactive ( voice/web ) response system . The pharmacist , treating physician , and coordinator at each site were unblinded , but the the follow-up team was completely blinded . The primary endpoint was a composite of all-cause death , cardiovascular admission to hospital , and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee . Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT01670981 . FINDINGS Between April 2 , 2013 , and Jan 28 , 2015 , 126 participants were r and omly assigned to receive either ixmyelocel-T ( n=66 ) or placebo ( n=60 ) . 114 ( 90 % ) patients comprised the modified intention-to-treat population and 109 ( 87 % ) patients were included in the per- protocol primary efficacy analysis ( 58 in the ixmyelocel-T group and 51 in the placebo group ) . The primary efficacy endpoint was observed in 47 patients : 50 events in 25 ( 49 % ) of 51 patients in the placebo group and 38 events in 22 ( 38 % ) of 58 patients in the ixmyelocel-T group , which represents a 37 % reduction in cardiac events compared with placebo ( risk ratio 0·63 [ 95 % CI 0·42 - 0·97 ] ; p=0·0344 ) . 41 ( 75 % ) of 51 participants in the placebo group had serious adverse events versus 31 ( 53 % ) of 58 in the ixmyelocel-T group ( p=0·0197 ) . INTERPRETATION To the best of our knowledge , ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far . The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy result ed in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes . FUNDING Vericel Corporation BACKGROUND Autologous bone marrow mononuclear cell ( ABMMNC ) therapy has shown promise in patients with heart failure ( HF ) . Cell function analysis may be important in interpreting trial results . METHODS In this prospect i ve study , we evaluated the safety and efficacy of the transendocardial delivery of ABMMNCs in no-option patients with chronic HF . Efficacy was assessed by maximal myocardial oxygen consumption , single photon emission computed tomography , 2-dimensional echocardiography , and quality -of-life assessment ( Minnesota Living with Heart Failure and Short Form 36 ) . We also characterized patients ' bone marrow cells by flow cytometry , colony-forming unit , and proliferative assays . RESULTS Cell-treated ( n = 20 ) and control patients ( n = 10 ) were similar at baseline . The procedure was safe ; adverse events were similar in both groups . Canadian Cardiovascular Society angina score improved significantly ( P = .001 ) in cell-treated patients , but function was not affected . Quality -of-life scores improved significantly at 6 months ( P = .009 Minnesota Living with Heart Failure and P = .002 physical component of Short Form 36 ) over baseline in cell-treated but not control patients . Single photon emission computed tomography data suggested a trend toward improved perfusion in cell-treated patients . The proportion of fixed defects significantly increased in control ( P = .02 ) but not in treated patients ( P = .16 ) . Function of patients ' bone marrow mononuclear cells was severely impaired . Stratifying cell results by age showed that younger patients ( ≤60 years ) had significantly more mesenchymal progenitor cells ( colony-forming unit fibroblasts ) than patients > 60 years ( 20.16 ± 14.6 vs 10.92 ± 7.8 , P = .04 ) . Furthermore , cell-treated younger patients had significantly improved maximal myocardial oxygen consumption ( 15 ± 5.8 , 18.6 ± 2.7 , and 17 ± 3.7 mL/kg per minute at baseline , 3 months , and 6 months , respectively ) compared with similarly aged control patients ( 14.3 ± 2.5 , 13.7 ± 3.7 , and 14.6 ± 4.7 mL/kg per minute , P = .04 ) . CONCLUSIONS ABMMNC therapy is safe and improves symptoms , quality of life , and possibly perfusion in patients with chronic HF BACKGROUND Our preliminary study suggested that patients with chronic myocardial infa rct ion ( MI ) and heart failure could potentially benefit from CABG combined with aBM-MNC by improving global left ventricular ( LV ) function . The purpose of this sub- study was to quantitatively evaluate the effectiveness of aBM-MNC transplantation during CABG in patients with chronic MI by intensively analyzing the global and segmental LV function , the scar , and the relationships between the function recovery and the scar transmural extent . METHODS A r and omized , double-blinded , placebo-controlled study was performed in 50 patients with chronic MI . The patients were r and omly allocated into CABG with stem cell transplantation ( group A ) and CABG only ( group B ) groups . CMR assessment s of global and segmental left ventricular function and scar tissue were performed before surgery and repeated at 12 months after CABG and aBM-MNC transplantation . RESULTS The left ventricular ejection fraction ( LVEF ) improved by 13.5 % and 8.0 % in group A and B respectively ( P=0.04 ) . Segmental analysis of regional LV function recovery indicated that more improvement in contractility was found in group A within the same degree of the infa rct transmurality ( P=0.017 ) and showed a predominant interaction in the most severely affected segments ( 76 - 100 % , P=0.016 ) . Decrease in infa rct size between the two groups did not reach statistical difference ( 9.4 % vs. 6.0 % , P=0.100 ) . CONCLUSIONS CMR assessment s revealed reversed ventricular remodeling and improved systolic function and scar reduction in patients who underwent aBM-MNC transplantation during CABG . And the conjunctional use of CABG and stem cell therapy could improve the left ventricular function in patients with chronic MI AIMS Pre- clinical and few clinical studies suggest that transplantation of autologous bone marrow mononuclear cells ( BMNC ) improves heart function in dilated cardiomyopathies . Our objective was to determine if intracoronary injection of autologous BMNC improves the left ventricular ejection fraction ( LVEF ) of patients with non-ischaemic dilated cardiomyopathy ( NIDCM ) . METHODS AND RESULTS This study was a multicentre , r and omized , double-blind , placebo controlled trial with a follow-up of 12 months . Patients with NIDCM and LVEF < 35 % were recruited at heart failure ambulatories in specialized hospitals around Brazil . One hundred and sixty subjects were r and omized to intracoronary injection of BMNC or placebo ( 1:1 ) . The primary endpoint was the difference in change of LVEF between BMNC and placebo groups as determined by echocardiography . One hundred and fifteen patients completed the study . Left ventricular ejection fraction decreased from 24.0 % ( 21.6 - 26.3 ) to 19.9 % ( 15.4 - 24.4 ) in the BMNC group and from 24.3 % ( 22.1 - 26.5 ) to 22.1 % ( 17.4 - 26.8 ) in the placebo group . There were no significant differences in changes between cell and placebo groups for left ventricular systolic and diastolic volumes and ejection fraction . Mortality rate was 20.37 % in placebo and 21.31 % in BMNC . CONCLUSION Intracoronary injection of autologous BMNC does not improve left ventricular function in patients with NIDCM . CLINICAL TRIAL REGISTRATION URL : http://www . clinical trials.gov . Unique identifier : NCT00333827 OBJECTIVES Cell therapy may offer novel therapeutic options for chronic ischemic heart disease . In a clinical trial , we first assessed the feasibility and safety of intramyocardial CD133 + bone marrow cell injection together with coronary artery bypass grafting ( CABG ) . We then tested the hypothesis that CABG plus CD133 + cell injection would result in better contractile function than CABG alone . METHODS Fifteen patients took part in the safety study , followed by 40 patients who underwent either CABG with cell therapy or CABG alone . Bone marrow was harvested from the iliac crest one day before surgery , and purified CD133 + progenitor cells were injected in the infa rct border zone during the CABG operation . LV function was measured by echocardiography and myocardial perfusion by SPECT . RESULTS In the safety study , no procedure-related complications were observed for up to 3 years . LV injection fraction ( LVEF ) increased from 39.0 % + /- 8.7 % preoperatively to 50.2 % + /- 8.5 % at 6 months and 47.9 % + /- 6.0 % at 18 months ( F = 6.03 , P = .012 ) . In the efficacy study , LCEF rose form 37.4 % + /- 8.4 % to 47.1 % + /- 8.3 % at 6 months in the group with CABG and cell therapy ( F = 24.16 , P < .0001 ) but only from 37.9 % + /- 10.3 % to 41.3 % + /- 9.1 % in the CABG-only group ( F = 7.72 , P = .012 ) . LVEF was significantly higher at 6 months in the group with CABG and cell therapy than in the CABG-only group ( P = .03 ) . Similarly , perfusion of the infa rct ed myocardium improved more in patients treated with CABG and cell therapy than in those treated with CABG alone . CONCLUSION Intramyocardial delivery of purified bone marrow stem cells together with CABG surgery is safe and provides beneficial effects , though it remains to be seen whether thewe effects produce a lasting clinical advantage BACKGROUND Mononuclear bone marrow cell ( MN- BMC ) transplantation has great clinical potential to promote myocardiogenesis and angiogenesis . This r and omized study was design ed to assess the feasibility and safety of MN- BMC transplantation during coronary artery bypass grafting ( CABG ) in patients with ischemic heart failure . METHODS Thirty-six patients were prospect ively enrolled and r and omized to a MN- BMC group ( n = 18 ) and a control group ( n = 18 ) . A mean number of 6.59 x 10(8 ) + /- 5.12 x 10(8 ) MN- BMC were injected into the infa rct ed and marginal areas during CABG in the MN- BMC group . The patients in the control group underwent CABG alone . All patients were followed up to 6 months . RESULTS There was one death in the MN- BMC group and no death in the control group . Two patients developed ventricular arrhythmia in the MN- BMC group . Compared with baseline and the control group , therapeutic effects of MN- BMC transplantation were observed over time . Heart function ( New York Heart Association ) was significantly improved and angina pectoris was alleviated in the MN- BMC group . Left ventricular ejection fraction in the MN- BMC group was greater than the control group . The thickness and motion velocity of the infa rct ed wall were significantly increased in the MN- BMC group . More pronounced perfusion improvements of ischemic regions and LV were observed in the MN- BMC group . There was one late death in the MN- BMC group . No procedure-related complications occurred . CONCLUSIONS MN- BMC transplantation improves cardiac function and regional perfusion in ischemic heart failure patients during CABG . A large cohort with long-term follow-up is needed to further evaluate the safety of MN- BMC transplantation AIMS Intra-myocardial transplantation of CD133(+ ) bone marrow stem cells ( BMC ) yielded promising results in clinical pilot trials . We now performed the double-blinded , r and omized , placebo-controlled CARDIO133 trial to determine its impact on left ventricular ( LV ) function and clinical symptoms . METHODS AND RESULTS Sixty patients with chronic ischaemic heart disease and impaired LV function ( left ventricular ejection fraction , LVEF < 35 % ) were r and omized to undergo either coronary artery bypass grafting ( CABG ) and injection of CD133(+ ) BMC in the non-transmural , hypokinetic infa rct border zone ( CD133 ) , or CABG and placebo injection ( placebo ) . Pre-operative LVEF was 27 ± 6 % in CD133 patients and 26 ± 6 % in placebo patients . Outcome was assessed after 6 months , and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging ( MRI ) at rest . The incidence of adverse events was similar in both groups . There was no difference in 6-min walking distance , Minnesota Living with Heart Failure score , or Canadian Cardiovascular Society ( CCS ) class between groups at follow-up , and New York Heart Association class improved more in the placebo group ( P = 0.004 ) . By cardiac MRI , LVEF at 6 months was 33 ± 8 % in the placebo group and 31 ± 7 % in verum patients ( P = 0.3 ) , with an average inter-group difference of -2.1 % ( 95 % CI -6.3 to 2.1 ) . Systolic or diastolic LV dimensions at 6 months were not different , either . In the CD133 group , myocardial perfusion at rest recovered in more LV segments than in the placebo group ( 9 vs. 2 % , P < 0.001 ) . Scar mass decreased by 2.2 ± 5 g in CD133(+ ) patients ( P = 0.05 ) , but was unchanged in the placebo group ( 0.3 ± 4 g , P = 0.7 ; inter-group difference in change = 2 g ( 95 % CI -1.1 to 5 ) ) . By speckle-tracking echocardiography , cell-treated patients showed a better recovery of regional wall motion when the target area was posterior . CONCLUSION Although there may be some improvements in scar size and regional perfusion , intra-myocardial injection of CD133(+ ) BMC has no effect on global LV function and clinical symptoms . Improvements in regional myocardial function are only detectable in patients with posterior infa rct ion , probably because the interventricular septum after anterior infa rct ion is not accessible by trans-epicardial injection . CLINICAL TRIAL REGISTRATION This trial was registered at http://www . clinical trials.gov under NCT00462774 BACKGROUND Bone marrow mononuclear cell ( BMMC ) transplantation for heart failure has shown inconsistent therapeutic efficacy . METHODS We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery ( CABG ) . After 4- to 12-week pharmacotherapy optimization , 39 patients with left ventricular ejection fraction ( LVEF ) of ≤45 % received injections of BMMC or vehicle intra-operatively into the myocardial infa rct ion border area in a r and omized , double-blind manner . RESULTS The median number of cells injected was 8.4 × 10(8 ) ( interquartile range [ IQR ] : 5.2 × 10(8 ) to 13.5 × 10(8 ) ) . We measured LV function and myocardial scar size by magnetic resonance imaging ( MRI ) , and viability by positron emission tomography ( PET ) and single-photon emission computed tomography ( SPECT ) , pre-operatively and after 1-year follow-up . LVEF , the pre-defined primary end-point measure , improved by a median of 5.6 % in the control group ( IQR 0.2 to 10.1 ) and by 4.8 % in the BMMC group ( IQR -0.5 to 8.2 ) ( p = 0.59 ) . Wall thickening in injected segments rose by a median of 4.5 % among controls ( IQR -18.1 to 23.9 ) and by 5.5 % in the BMMC group ( IQR -6.6 to 26.5 ) ( p = 0.68 ) . Changes in viability by PET and SPECT did not differ between groups . Myocardial scar size by MRI in injected segments rose by a median of 5.1 % among controls ( IQR -3.3 to 10.8 ) , but fell by 13.1 % in the BMMC group ( IQR -21.4 to -6.5 ) ( p = 0.0002 ) . CONCLUSIONS BMMC therapy combined with CABG failed to improve LV systolic function , or viability , despite reducing myocardial scar size AIMS Regenerative treatment with mesenchymal stromal cells ( MSCs ) has been promising in patients with ischaemic heart failure but needs confirmation in larger r and omized trials . We aim ed to study effects of intra-myocardial autologous bone marrow-derived MSC treatment in patients with severe ischaemic heart failure . METHODS AND RESULTS The MSC-HF trial is a r and omized , double-blind , placebo-controlled trial . Patients were r and omized 2 : 1 to intra-myocardial injections of MSC or placebo , respectively . The primary endpoint was change in left ventricular end-systolic volume ( LVESV ) , measured by magnetic resonance imaging or computed tomography at 6 months follow-up . Sixty patients aged 30 - 80 years with severe ischaemic heart failure , New York Heart Association ( NYHA ) classes II-III , left ventricular ejection fraction ( LVEF ) < 45 % and no further treatment options were r and omized . Fifty-five patients completed the 6-month follow-up ( 37 MSCs vs. 18 placebo ) . At 6 months , LVESV was reduced in the MSC group : -7.6 ( 95 % CI -11.8 to -3.4 ) mL ( P = 0.001 ) , and increased in the placebo group : 5.4 ( 95 % CI -0.4 to 11.2 ) mL ( P = 0.07 ) . The difference between groups was 13.0 ( 95 % CI 5.9 - 20.1 ) mL ( P = 0.001 ) . Compared with placebo , there were also significant improvements in LVEF of 6.2 % ( P<0.0001 ) , stroke volume of 18.4 mL ( P < 0.0001 ) , and myocardial mass of 5.7 g ( P = 0.001 ) . No differences were found in NYHA class , 6-min walking test and Kansas City cardiomyopathy question naire . No side effects were identified . CONCLUSION Intra-myocardial injections of autologous culture exp and ed MSCs were safe and improved myocardial function in patients with severe ischaemic heart failure . STUDY REGISTRATION NUMBER NCT00644410 ( Clinical Trials.gov ) CONTEXT Previous studies using autologous bone marrow mononuclear cells ( BMC s ) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy . OBJECTIVE To determine if administration of BMC s through transendocardial injections improves myocardial perfusion , reduces left ventricular end-systolic volume ( LVESV ) , or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction , and limiting heart failure or angina . DESIGN , SETTING , AND PATIENTS A phase 2 r and omized double-blind , placebo-controlled trial of symptomatic patients ( New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV ) with a left ventricular ejection fraction of 45 % or less , a perfusion defect by single-photon emission tomography ( SPECT ) , and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart , Lung , and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network ( CCTRN ) sites between April 29 , 2009 , and April 18 , 2011 . INTERVENTION Bone marrow aspiration ( isolation of BMC s using a st and ardized automated system performed locally ) and transendocardial injection of 100 million BMC s or placebo ( ratio of 2 for BMC group to 1 for placebo group ) . MAIN OUTCOME MEASURES Co- primary end points assessed at 6 months : changes in LVESV assessed by echocardiography , maximal oxygen consumption , and reversibility on SPECT . Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory . RESULTS Of 153 patients who provided consent , a total of 92 ( 82 men ; average age : 63 years ) were r and omized ( n = 61 in BMC group and n = 31 in placebo group ) . Changes in LVESV index ( -0.9 mL/m(2 ) [ 95 % CI , -6.1 to 4.3 ] ; P = .73 ) , maximal oxygen consumption ( 1.0 [ 95 % CI , -0.42 to 2.34 ] ; P = .17 ) , and reversible defect ( -1.2 [ 95 % CI , -12.50 to 10.12 ] ; P = .84 ) were not statistically significant . There were no differences found in any of the secondary outcomes , including percent myocardial defect , total defect size , fixed defect size , regional wall motion , and clinical improvement . CONCLUSION Among patients with chronic ischemic heart failure , transendocardial injection of autologous BMC s compared with placebo did not improve LVESV , maximal oxygen consumption , or reversibility on SPECT . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00824005 OBJECTIVES The aim of this study was to test safety and feasibility of myoblast transplantation with the Biosense-NOGA ( Diamond Bar , California ) 3-dimensional-guided endomyocardial delivery system . BACKGROUND Previous Phase-1 trials showed feasibility of epicardial injection of myoblasts . However , catheter-based delivery has several advantages : it can be applied on high-risk patients , the procedure can be repeated , and it is associated with less morbidity and mortality . METHODS Twenty-three subjects , with previous myocardial infa rct ion and heart failure , New York Heart Association ( NYHA ) functional class II to IV , were enrolled , 11 control and 12 treatment subjects . To assess safety , physical exam , electrocardiogram , continuous rhythm monitoring , quality of life assessment s , and heart function were evaluated at baseline and follow-up until 1 year . RESULTS There was favorable safety : no difference between groups in arrhythmias , and no deaths . Treated subjects showed sustained improvements in NYHA and Minnesota Living with Heart Failure Question naire ( MLHFQ ) compared with control subjects ( NYHA , -1.0 point in treatment vs. + 0.3 point in control group , p < 0.0004 ; MLHFQ , -14 point in treatment vs. + 1 point in the control group , p = 0.004 ) . Blinded core laboratory echocardiography evaluations showed sustained reductions in the treatment versus control in end diastolic diameter ( -0.03 cm vs. + 0.05 cm , p = 0.07 ) and end systolic diameter ( -0.05 cm vs. + 0.1 cm , p = 0.07 ) . Finally , NOGA voltage mapping demonstrated improved voltage measurements ( + 1.0 mV , p = 0.008 ) . CONCLUSIONS This trial of myoblast transplantation via catheter into heart failure patients demonstrated safety and feasibility . Treated patients showed improvement in NYHA , MLHFQ , ventricular viability , and evidence of reverse ventricular remodeling . These data demonstrate positive safety outcomes and warrant initiation of larger phase 2 , double-blind , placebo-controlled clinical trials |
2,143 | 24,418,303 | LA and aCL were significantly associated with an increased risk of thrombosis , especially arterial , in patients without SLE . | AIM To evaluate the magnitude of venous and arterial thrombosis risk associated with antiphospholipid antibodies ( APLs ) in adults without systemic lupus erythematosus ( SLE ) . | Summary . Anticardiolipin antibodies , one of the family of ‘ antiphospholipid ’ antibodies , increase the risk of venous thromboembolism in the presence of autoimmune disease . Our objective was to determine prospect ively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults . We conducted a nested case – control study ( n = 317 patients and n = 655 control subjects ) in a longitudinal study of over 20 000 participants . Baseline ( prediagnosis ) anticardiolipin IgG and IgM antibodies were assessed by enzyme‐linked immunoassays . Venous thromboembolism was vali date d using st and ardized criteria for venous thrombosis and pulmonary embolism . There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence , overall or in any subgroup . For example , the multivariate‐adjusted relative risk was 0·88 ( 95 % confidence interval , 0·43 , 1·78 ) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion , in this general population sample , an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism Introduction – We have undertaken a prospect i ve study to measure anticardiolipin antibodies of IgG isotype within the first few hours of an acute non‐hemorrhagic stroke . Material and methods – We have collected blood sample s at entry from one hundred patients ( 53 men and 47 women ) , mean age 67.4 years , referred within 6 h of a first‐ever non‐hemorrhagic stroke , and from an equal number of age‐ and gender‐matched control patients . Results – IgG anticardiolipin antibodies were 10 GPL in 26 patients and in 5 controls ( p < 0.0001 , X2 test ) . After logistic regression analysis , increase of IgG anticardiolipin antibodies remained independently associated with stroke ( p = 0.0034 ) , together with hypertension ( p = 0.0009 ) and atrial fibrillation ( p = 0.0238 ) . Conclusion – Our data suggest that the occurrence of elevation of IgG anticardiolipin antibodies in stroke patients should ante date stroke onset and might be a risk factor per se OBJECTIVE To determine whether the presence of anticardiolipin antibodies is a risk factor for ischemic stroke and venous thrombosis in healthy adult men . DESIGN A nested , case-control study in a prospect i ve cohort . SETTING A nationwide study of physicians . PARTICIPANTS The study sample was drawn from the Physicians ' Health Study , a r and omized , double-blind , placebo-controlled trial of aspirin and beta-carotene in 22,071 male physicians . At entry , 68 % of the participants su bmi tted plasma sample s that were subsequently frozen at -80 degrees C. During 60.2 months of follow-up , follow-up for nonfatal outcomes was 99.7 % complete and ascertainment of fatal outcomes was 100 % complete . We identified men with documented ischemic stroke , deep venous thrombosis of the leg , or pulmonary embolus and for whom a plasma sample was available . A control was matched by age , smoking history , and length of follow-up to each of the 100 patients with ischemic stroke and the 90 patients with deep venous thrombosis or pulmonary embolus . MEASUREMENTS Plasma sample s were assessed for IgG anticardiolipin antibodies by enzyme-linked immunosorbent assay . The mean anticardiolipin antibody titers of the case patients in the two diagnostic groups ( ischemic stroke ; venous thrombosis or pulmonary embolus ) were compared with those of the control groups , and relative risks were calculated for patients in increasing percentile categories of anticardiolipin antibodies by conditional logistic regression . RESULTS The anticardiolipin antibody titers were higher in case patients with deep venous thrombosis and pulmonary embolus than in their matched controls ( P = 0.01 ) . Persons with anticardiolipin antibody titers above the 95th percentile had a relative risk for developing deep venous thrombosis or pulmonary embolus of 5.3 ( 95 % CI , 1.55 to 18.3 ; P = 0.01 ) . The anticardiolipin antibody titers in case patients with ischemic stroke and controls were not significantly different ( P > 0.2 ) , and no clear trend of higher risks among those with elevated levels of anticardiolipin antibodies was observed . CONCLUSION An anticardiolipin antibody level above the 95th percentile is an important risk factor for deep venous thrombosis or pulmonary embolus but not for ischemic stroke in healthy adult men CONTEXT The presence of antiphospholipid antibodies ( aPL ) has been associated with vascular occlusive events . However , the role of aPL in predicting ischemic events , particularly recurrent ischemic stroke , is controversial . OBJECTIVE To evaluate the effect of baseline aPL positivity ( ie , positivity for anticardiolipin antibodies [ aCL ] , lupus anticoagulant antibodies [ LA ] , or both ) on subsequent thrombo-occlusive events , including recurrent stroke . DESIGN , SETTING , AND PARTICIPANTS The Antiphospholipid Antibodies and Stroke Study ( APASS ) , a prospect i ve cohort study within the Warfarin vs Aspirin Recurrent Stroke Study ( WARSS ) , a r and omized double-blind trial ( N = 2206 ) conducted at multiple US clinical sites from June 1993 through June 2000 and comparing adjusted-dose warfarin ( target international normalized ratio , 1.4 - 2.8 ) and aspirin ( 325 mg/d ) for prevention of recurrent stroke or death . APASS participants were 1770 ( 80 % ) WARSS participants who consented to enroll in the APASS , with usable baseline blood sample s drawn prior to r and omization to the WARSS and analyzed for aPL status within 90 days of index stroke by a central independent laboratory . Quality assurance was performed on approximately 10 % of sample s by a second independent laboratory . MAIN OUTCOME MEASURE Two-year rate of the composite end point of death from any cause , ischemic stroke , transient ischemic attack , myocardial infa rct ion , deep vein thrombosis , pulmonary embolism , and other systemic thrombo-occlusive events . The primary analysis assessed the outcome associated with aPL positivity within each WARSS treatment group separately , after risk-factor adjustment ( since these aPL-positive vs aPL-negative comparisons were not r and omized ) . RESULTS Of the 1770 APASS patients , 720 ( 41 % ) were classified as aPL-positive and 1050 ( 59 % ) as aPL-negative . There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.75 - 1.31 ; P = .94 ) , or aspirin ( RR , 0.94 ; 95 % CI , 0.70 - 1.28 ; P = .71 ) . The overall event rate was 22.2 % among aPL-positive and 21.8 % among aPL-negative patients . There was no treatment x aPL interaction ( P = .91 ) . Patients with baseline positivity for both LA and aCL antibodies tended to have a higher event rate ( 31.7 % ) than did patients who tested negative for both antibodies ( 24.0 % ) ( unadjusted RR , 1.36 ; 95 % CI , 0.97 - 1.92 ; P = .07 ) . Classification and regression tree analyses did not identify a specific LA test or aCL isotype or titer that was associated with increased risk of thrombo-occlusive event . CONCLUSIONS The presence of aPL ( either LA or aCL ) among patients with ischemic stroke does not predict either increased risk for subsequent vascular occlusive events over 2 years or a differential response to aspirin or warfarin therapy . Routine screening for aPL in patients with ischemic stroke does not appear warranted OBJECTIVE We carried out a prospect i ve analysis of clinical and analytical findings in individuals with antiphospholipid antibodies ( aPL ) . METHODS We prospect ively studied 404 individuals , classified in 2 groups : ( 1 ) patients with primary or secondary antiphospholipid syndrome ( APS , n = 226 ) ; and ( 2 ) asymptomatic carriers of aPL ( n = 178 ) . Patients with APS and thrombosis were treated with dicumarin , and an international normalized ratio around 3.0 ( range 2.5 - 3.5 ) was targeted . Asymptomatic carriers were not treated , but specific prophylaxis with low molecular weight heparin or aspirin was prescribed for the periods when individuals were at increased risk of thrombosis . Both groups of individuals were followed up at semester intervals for 36 months . RESULTS Patients with APS presented with venous ( n = 106 , 46.9 % ) and /or arterial ( n = 70 . 31 % ) thrombosis or fetal loss ( n = 58 out of 112 women of fertility age , 51.8 % ) . At the time of the first thrombotic event , 50.0 % of patients with APS had coincident risk factors for thrombosis ( previous surgery and prolonged immobilization were significantly associated with venous thrombosis , and hypercholesterolemia and arterial hypertension with arterial thrombosis ) . Eighteen patients with APS died during the study period . Recurrence of thrombosis in patients with APS was linked to insufficient anticoagulation . During the followup , no episode of thrombosis was detected in any asymptomatic carrier . The proportion of subjects with aPL was similar in patients and in asymptomatic carriers . The proportion of subjects with aPL decreased during the followup , in both patients and carriers . CONCLUSION Differences between patients and asymptomatic carriers with aPL are at least partially dependent on the proportion of coincident vascular risk factors . The decline in aPL during the followup defines a subgroup in which an anticoagulation suppression assay could be tried Our aim was to determine if anticardiolipin antibodies are an independent risk factor for ischemic stroke and to determine their influence on stroke type and clinical outcome . We prospect ively studied 194 consecutive patients with ischemic stroke admitted within 48 h of stroke . A control group consisted of 100 , age and sex matched , healthy individuals . Neurological and functional status was assessed on admission , at 30 days , and at 1 year . IgG anticardiolipin antibodies were significantly more frequent in stroke patients ( 25.3 % ) than controls ( 6 % , p < 0.05 ) . A multivariate analysis suggested that anticardiolipin antibodies are an independent risk factor for ischemic stroke in addition to hypertension and atrial fibrillation ( RR = 2.94 , p < 0.05 ) . Elevated IgG anticardiolipin antibodies were associated with cognitive impairment as measured by the Mini Mental State Examination at 30 days and at 1 year . IgG anticardiolipin antibodies did not correlate with stroke recurrence , or mortality at 30 days or 1 year To date very few studies that analyze the prevalence of anticardiolipin antibodies ( ACA ) in healthy subjects have been reported . No data based on a systematic analysis of normal subjects with positive ACA is available . The aim of the present study was to evaluate the prevalence of ACA ; its clinical significance and relationship to the lupus anticoagulant ( LA ) and other autoimmune parameters in an apparently healthy population . 552 normal blood donors from a blood bank were r and omly selected . ACA positive donors who consented were monitored over a period of twelve months and tested every three months . ACA ( IgG and IgM isotypes ) were quantitated by enzyme linked immunoassay ( ELISA ) . The prevalence for IgG ACA in our donor population was estimated to be 6.5 % , and 9.4 % for IgM ACA , which is similar to the one previously reported for IgG and slightly higher for IgM. It is worth noting that in our study ACA positive donors exhibited a progressive negativization . Eight donors with IgG ACA and seven with IgM ACA remained positive for nine months . Five donors with IgG ACA and four with IgM ACA had family history of thromboembolic disease . One donor with IgG ACA and two with IgM ACA had had unexplained miscarriages in the past . We did not find any relationship between ACA and LA , nor between ACA positivity and the clinical and laboratory data studied . Pseudopositivity for lues was not found . No thrombotic event occurred in donors that were positive for ACA during the 12-month follow-up PURPOSE To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies . PATIENTS AND METHODS Three hundred sixty consecutive patients ( 118 males , 242 females , median age 39 years [ range 2 to 78 ] ) fulfilling the currently accepted criteria for diagnosis of lupus anticoagulant ( LAC ) ( n = 326 ) and /or raised immunoglobulin G anticardiolipin antibodies ( IgG ACA ) ( n = 185 ) were collected from 16 Italian institutions and prospect ively observed for a median of 3.9 years ( range 0.5 to 5 ) . Main endpoints were the occurrence of arterial or venous thrombosis , the outcome of pregnancies , and any severe complications leading to hospitalization or death . RESULTS Thirty-four patients developed a thrombotic complication , with a total incidence of 2.5 % patient-years . Multivariate logistic regression analysis identified two independent risk factors for thrombotic events : a previous thrombosis ( RR 4.9 ; 95 % CI , 1.76 to 13.7 ; P < 0.005 ) and IgG ACA titer above 40 units ( RR 3.66 ; 95 % CI , 1.24 to 10.8 ; P < 0.01 ) . A total of 28 pregnancies were observed in 25 women and 11 ( 39 % ) were abortive . Adverse pregnancy outcomes were significantly more frequent in women with a history of miscarriage or vascular occlusion ( 9/16 , 56 % ) than in asymptomatic women ( 2/12 , 17 % ) ( P = 0.035 ) . Four patients developed non-Hodgkin 's lymphoma during the follow-up . Eighteen patients died . Vascular events and hematological malignancies represented the most frequent causes of death ( n = 5 for each ) . CONCLUSIONS The present study shows that : ( a ) previous thrombosis and ACA titer > 40 U are independent predictors of thrombosis ; ( b ) history of miscarriage or vascular disease is significantly associated with adverse pregnancy outcome ; ( c ) hematological malignancies can develop during follow-up in patients with antiphospholipid antibodies Antibodies against phospholipid-binding plasma proteins , such as beta2-glycoprotein I ( beta2-GPI ) and prothrombin , are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases . We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids ( cardiolipin ) , to phospholipid-binding plasma proteins beta2-GPI and prothrombin and to oxidised low-density lipoprotein ( LDL ) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis . The antibodies were measured in stored serum sample s from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls . The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register . The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies . As adjusted for body mass index , number of daily cigarettes and history of chronic bronchitis , myocardial infa rct ion and heart failure at baseline , the odds ratio per one unit of antibody was 6.56 ( 95 % confidence interval 1.73 - 25.0 ) . The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes . In conclusion , the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes We prospect ively examined whether there is an association between elevated anticardiolipin antibody levels and the risk for a future first venous thrombosis ( VT ) in a general population . We studied this in a large population -based nested case-cohort study of 508 VT cases and 1464 matched control subjects from a cohort of 66,140 participants in the Health Study of Nord-Trøndelag in Norway . Venous thrombosis was vali date d using st and ardized criteria for venous thrombosis and pulmonary embolism . Prethrombotic serum anticardiolipin antibodies were measured by an enzyme-linked immunoassay . There was no association between elevated anticardiolipin antibody levels and subsequent venous thrombosis , overall or after stratification by sex , different age groups or idiopathic vs. secondary thrombosis . The overall odds ratio was 1.11 ( 95 % CI : 0.71 - 1.74 ) for greater than vs. less than the 95th percentile of anticardiolipin antibody levels . In conclusion , in this general population sample elevated anticardiolipin antibody levels was not a risk factor for subsequent venous thrombosis We undertook a prospect i ve study of consecutive patients to determine the frequency of elevated IgG and IgM anticardiolipin antibodies in transient ischemie attack and ischemie stroke and found elevated IgG antibodies in 8.2 % ( 9 of 110 ) and IgM in 9.1 % ( 10 of 110 ) , only the former being significantly greater than in a healthy control population . We suggest that anticardiolipin screening be concentrated on the young Primary antithrombotic prevention with aspirin is not indicated in asymptomatic patients with confirmed antiphospholipid ( aPL ) positivity without systemic autoimmune disorders because : a ) the estimated prevalence of thrombosis in unselected cases is about 1 % patient-years ( range 0–2.8 ) ; b ) this level of thrombotic risk is equivalent to that of major bleeding associated with the use of aspirin and therefore the expected benefit does not outweigh the risk ; c ) these expectations have been confirmed by at least one r and omized clinical trial , although with method ological limits . The management of modifiable thrombotic risk factors can be an alternative and safer strategy , considering that many vascular events occur in the presence of concomitant non-aPL triggering conditions . Whether primary prophylaxis with aspirin may be useful for some subsets of aPL patients at particularly high thrombotic risk , such as those with overt systemic autoimmune disorders or with special patterns of antibodies ( ‘ triple positivity ’ ) , remains to be established A pathogenetic role in thrombotic disease , particularly in young people , has been postulated for anticardiolipin antibody ( ACA ) . We have carried out a prospect i ve controlled study of 262 unselected patients with acute stroke and 226 controls to assess the prevalence and relation to age and vascular risk factors of ACA . Titres of IgG , IgA , or IgM ACA were above the upper normal limit in 38 % of patients . The proportions of patients and controls with raised titres did not differ significantly ( 13 vs 8 % IgG , 22 vs 29 % IgA , 11 vs 7 % IgM ) . IgG titres were higher among patients than among controls ( mean 3.88 vs 2.86 u/mL [ 95 % CI for difference 0.62 - 0.87 ] , p = 0.0004 ) , whereas IgA and IgM titres were lower in patients than in controls ( IgA 4.82 vs 5.98 u/mL [ 1.12 - 1.60 ] , p = 0.01 ; IgM 3.00 vs 3.64 u/mL [ 1.01 - 1.45 ] , p = 0.04 ) . However , within age tertiles the only significant difference between patients and controls for IgG ACA was in the oldest tertile . Analysis by number of risk factors for stroke showed a significant difference between the groups only for subjects with one risk factor . IgA and IgM ACA titres were higher among controls only in those with no vascular risk factors . We found no evidence to support the hypothesis that ACA is an independent risk factor for stroke in young people . The increase in IgG titre with age and number of vascular risk factors in stroke patients suggests that ACA may be a non-specific accompaniment of vascular disease . Routine testing for ACA in stroke patients is not justified OBJECTIVE To determine the efficacy of a daily dose of 81 mg aspirin in primary thrombosis prevention in asymptomatic , persistently antiphospholipid antibody (aPL)-positive individuals ( those with positive aPL but no vascular and /or pregnancy events ) . METHODS The Antiphospholipid Antibody Acetylsalicylic Acid ( APLASA ) study was a multicenter , r and omized , double-blind , placebo-controlled clinical trial in which asymptomatic , persistently aPL-positive individuals were r and omized to receive a daily dose of 81 mg of aspirin or placebo . In a separate observational and parallel study , asymptomatic , persistently aPL-positive individuals who were taking aspirin or declined r and omization were followed up prospect ively . RESULTS In the APLASA study , 98 individuals were r and omized to receive aspirin or placebo ( mean + /- SD followup period 2.30 + /- 0.95 years ) , of whom 48 received aspirin and 50 received placebo . In the observational study , 74 nonr and omized individuals were followed up prospect ively ( mean + /- SD followup period 2.46 + /- 0.76 years ) ; 61 received aspirin and 13 did not . In the APLASA study , the acute thrombosis incidence rates were 2.75 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for the placebo-treated subjects ( hazard ratio 1.04 , 95 % confidence interval 0.69 - 1.56 ) ( P = 0.83 ) . Similarly , in the observational study , the acute thrombosis incidence rates were 2.70 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for those not treated with aspirin . All but 1 patient with thrombosis in either study had concomitant thrombosis risk factors and /or systemic autoimmune disease at the time of thrombosis . CONCLUSION Our results suggest that asymptomatic , persistently aPL-positive individuals do not benefit from low-dose aspirin for primary thrombosis prophylaxis , have a low overall annual incidence rate of acute thrombosis , and develop vascular events when additional thrombosis risk factors are present |
2,144 | 27,055,877 | The little available evidence suggested increased levels of dementia being associated with reduced tolerability .
CONCLUSIONS ABPM is well tolerated in people with mild-moderate dementia and provides some additional information over and above office BP alone .
However , few studies have addressed ABPM in people with more severe dementia | BACKGROUND ambulatory blood pressure monitoring ( ABPM ) may be helpful for the management of hypertension , but little is known about its tolerability in people with dementia .
OBJECTIVE to review the published evidence to determine the tolerability of ABPM in people with dementia . | OBJECTIVES To determine the prognostic role of orthostatic hypotension for cardiovascular disease ( CVD ) and all-cause mortality in elderly people . DESIGN Prospect i ve study . SETTING Community based . PARTICIPANTS Five thous and sixty-four subjects from the Rotterdam study aged 55 and older . MEASUREMENTS Orthostatic hypotension was measured using a Dinamap automatic blood pressure recorder . Orthostatic hypotension is defined as a decline in systolic blood pressure of 20 mmHg or more or a decline in diastolic blood pressure of 10 mmHg or more from supine to st and ing position at any of three measurements taken 1 , 2 , and 3 minutes after st and ing . RESULTS At baseline , 901 subjects had orthostatic hypotension . During follow-up , 668 subjects had coronary heart disease ( CHD ) ( mean follow-up 6.0 + /- 3.5 years ) , and 1,835 subjects died ( mean follow-up period 7.8 + /- 3.8 years ) . Orthostatic hypotension increased the risk of CHD ( hazard ratio (HR)=1.31 , 95 % confidence interval (CI)=1.08 - 1.57 ) and all-cause mortality ( HR=1.22 , 95 % CI=1.09 - 1.36 ) , in models adjusted for age and sex . The risk was slightly lower after additional adjustment for cardiovascular risk factors . In analyses stratified for age , the HRs for all-cause mortality were 1.80 ( 95 % CI 1.25 - 2.60 ) , 1.13 ( 0.89 - 1.42 ) , and 1.27 ( 95 % CI=1.11 - 1.44 ) , in the first , second , and third tertile of age , respectively . CONCLUSION Orthostatic hypotension increases the risk of CHD and all-cause mortality in elderly people . The risk of CVD and mortality is strongest in younger and very old subjects Background Falls are a major cause of morbidity and mortality in dementia , but there have been no prospect i ve studies of risk factors for falling specific to this patient population , and no successful falls intervention/prevention trials . This prospect i ve study aim ed to identify modifiable risk factors for falling in older people with mild to moderate dementia . Methods and Findings 179 participants aged over 65 years were recruited from outpatient clinics in the UK ( 38 Alzheimer 's disease ( AD ) , 32 Vascular dementia ( VAD ) , 30 Dementia with Lewy bodies ( DLB ) , 40 Parkinson 's disease with dementia ( PDD ) , 39 healthy controls ) . A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospect ively for 12 months . Dementia participants experienced nearly 8 times more incident falls ( 9118/1000 person-years ) than controls ( 1023/1000 person-years ; incidence density ratio : 7.58 , 3.11–18.5 ) . In dementia , significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder ( proportional hazard ratio ( HR ) adjusted for age and sex : 3.33 , 2.11–5.26 ) , and history of falls in the preceding 12 months ( HR : 2.52 , 1.52–4.17 ) . In multivariate analyses , significant potentially modifiable predictors were symptomatic orthostatic hypotension ( HR : 2.13 , 1.19–3.80 ) , autonomic symptom score ( HR per point 0–36 : 1.055 , 1.012–1.099 ) , and Cornell depression score ( HR per point 0–40 : 1.053 , 1.01–1.099 ) . Higher levels of physical activity were protective ( HR per point 0–9 : 0.827 , 0.716–0.956 ) . Conclusions The management of symptomatic orthostatic hypotension , autonomic symptoms and depression , and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia . R and omised controlled trials to assess such a strategy are a priority BACKGROUND Previous studies have reported a higher prevalence of dementia in persons with low blood pressure . OBJECTIVE To examine whether low blood pressure is prospect ively associated with the occurrence of Alzheimer disease and dementia in elderly people . SUBJECTS AND METHODS A community-based , dementia-free cohort ( n = 1270 ) aged 75 to 101 years was longitudinally examined twice within 6 years to detect incident dementia using the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition criteria . Cox proportional hazards models were used to analyze blood pressure in association with dementia after adjustment for several potential confounders . RESULTS During the 6-year period , 339 subjects were diagnosed with dementia , including 256 persons with Alzheimer disease . Subjects with very high systolic pressure ( > 180 vs 141 - 180 mm Hg ) had an adjusted relative risk of 1.5 ( 95 % confidence interval [ CI ] , 1.0 - 2.3 ; P = .07 ) for Alzheimer disease , and 1.6 ( 95 % CI , 1.1 - 2.2 ) for dementia . Low systolic pressure ( < /=140 mm Hg ) was not related to incident dementia . In contrast , high diastolic pressure ( > 90 mm Hg ) was not associated with dementia incidence , whereas extremely low diastolic pressure ( < /=65 vs 66 - 90 mm Hg ) produced an adjusted relative risk of 1.7 ( 95 % CI , 1.1 - 2.4 ) for Alzheimer disease and 1.5 ( 95 % CI , 1.0 - 2.1 ; P = .03 ) for dementia . The latter association was pronounced particularly in persons who used antihypertensive drugs . CONCLUSIONS Both low diastolic and high systolic pressure are associated with an increased risk of Alzheimer disease and dementia in this elderly population . The atherosclerotic process may explain the observed associations . In addition , low diastolic pressure may increase dementia risk by affecting cerebral perfusion Background and Purpose — A long-term follow-up study was conducted in patients with lacunar infa rct to assess how 24-hour blood pressure monitoring values and MRI findings , in particular lacunar infa rcts and diffuse white matter lesions , can predict subsequent development of dementia and vascular events , which include cerebrovascular and cardiovascular events . Methods — One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up . Documented events comprise the development of dementia and the occurrence of vascular events . The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis . Results — Twenty-six patients developed dementia ( 0.17/100 patient-years ) . Male sex ( relative risk [ RR ] , 4.2 ; 95 % CI , 1.2 to 14.7 ) , cognitive impairment ( RR , 3.0 ; 95 % CI , 1.0 to 8.5 ) , confluent DWML ( moderate : RR , 7.1 ; 95 % CI , 1.6 to 31.5 ; severe : RR , 35.8 ; 95 % CI , 7.2 to 177.3 ) , and nondipping status ( RR , 7.1 ; 95 % CI , 2.2 to 22.0 ) were independent predictors for dementia . Forty-six patients suffered from vascular events ( 3.11/100 patient-years ) . Diabetes mellitus ( RR , 5.7 ; 95 % CI , 2.7 to 11.9 ) , multiple lacunae ( moderate : RR , 6.4 ; 95 % CI , 2.5 to 15.8 ; severe : RR , 8.5 ; 95 % CI , 3.1 to 23.3 ) , and high 24-hour systolic blood pressure ( > 145 mm Hg versus < 130 mm Hg ) ( RR , 10.3 ; 95 % CI , 1.3 to 81.3 ) were independent predictors for vascular events . Conclusions — Predictors for developing dementia and vascular events appear to differ . Male sex , confluent diffuse white matter lesions , and nondipping status were independent predictors for subsequent development of dementia , while diabetes mellitus , multiple lacunae , and high 24-hour systolic blood pressure were independent predictors for vascular events Objectives Home blood pressure measurement ( HBPM ) is recommended by guidelines for hypertension management . However , this method might be difficult to use in elderly individuals with cognitive disorders . Our aim was to assess the agreement and the feasibility of HBPM by a relative as compared with 24-h ambulatory blood pressure monitoring ( ABPM ) in elderly patients with dementia . Methods Sixty out patients with dementia aged 75 years and older with office hypertension ( ≥140/90 mmHg ) were subjected successively to HBPM by a trained relative and 24-h ABPM . The order of the two methods was r and omized . Current guidelines ’ thresholds for the diagnosis of hypertension were used . Results The mean ( SD ) age of the patients was 80.8 ( 6.1 ) years ( 55 % women ) and the mean ( SD ) mini-mental state examination score was 20.1 ( 6.9 ) . The feasibility of relative-HBPM was very high , with a 97 % success rate ( defined by ≥12/18 measurements reported ) . The blood pressure measurements were highly correlated between the two methods ( r=0.75 and 0.64 for systolic blood pressure and diastolic blood pressure , respectively ; P<0.001 for both ) . The agreement between the methods for the diagnosis of sustained hypertension and white-coat hypertension was excellent ( overall agreement , 92 % ; & kgr ; coefficient , 0.81 ; 95 % CI , 0.61–0.93 ) . Similar results were found for daytime-ABPM . Conclusion In cognitively impaired elderly patients , HBPM by a relative using an automated device was a good alternative to 24-h ABPM Background : The role of blood pressure ( BP ) as a risk factor for dementia is complex and may be age dependent . In very old individuals , low BP might increase risk for dementia , perhaps by reducing cerebral perfusion pressure . Methods : The association between BP and dementia was examined in the Bronx Aging Study , a prospect i ve study of 488 community-dwelling elderly individuals over age 75 , dementia-free at baseline ( 1980 to 1983 ) and followed at 12- to 18-month intervals . Subjects with baseline BP and with at least one follow-up visit were included ( n = 406 ) . Incident dementia was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders ( 3rd rev . ed . ) . Results : Over 21 years ( median 6.7 years ) , 122 subjects developed dementia ( 65 Alzheimer ’s disease [ AD ] , 28 vascular dementia , 29 other dementias ) . Relative risk of dementia increased for each 10-mm Hg decrement in diastolic ( hazard ratio [ HR ] 1.20 , 95 % CI 1.03 to 1.40 ) and mean arterial ( HR 1.16 , 95 % CI 1.02 to 1.32 ) pressure , adjusted for age , sex , and education . Low diastolic BP significantly influenced risk of developing AD but not vascular dementia . Upon examination of groups defined by BP , mildly to moderately raised systolic BP ( 140 to 179 mm Hg ) was associated with reduced risk for AD ( HR vs normal systolic BP group 0.55 , 95 % CI 0.32 to 0.96 ) , whereas low diastolic BP ( ≤70 mm Hg ) was associated with increased risk of AD ( HR vs normal diastolic BP group 1.91 , 95 % CI 1.05 to 3.48 ) . Subjects with persistent low BP over 2 years had higher risk of developing dementia ( HR 2.19 , 95 % CI 1.27 to 3.77 ) . Conclusions : Low diastolic pressure is associated with higher risk of dementia in elderly individuals over age 75 . Dementia risk was higher in subjects with persistently low BP Antihypertensive therapy based on the angiotensin-converting enzyme ( ACE ) inhibitor perindopril reduced the incidence of recurrent stroke in the Perindopril Protection against Recurrent Stroke Study ( PROGRESS ) . The present study assessed the effect of perindopril on the 24-h blood pressure ( BP ) in hypertensive patients with lacunar infa rct ion using ambulatory BP monitoring ( ABPM ) . There was a 4-week observation period , a 4-week treatment period 1 ( perindopril at 2 mg/day ) , and a 4-week treatment period 2 ( perindopril at 4 mg/day ) . Twenty-seven hypertensive patients with lacunar infa rct ion ( 10 dippers and 17 non-dippers ) were enrolled . The average 24-h BP values were significantly decreased after both treatment periods . When the patients were divided into dippers and non-dippers , perindopril exhibited a different BP-lowering effect in the groups with these two circadian BP patterns . In dippers , daytime BP was significantly decreased , whereas nighttime BP was not , so an excessive fall of nighttime BP was not observed . In non-dippers , both daytime and nighttime BP were decreased , with a stronger BP-lowering effect at night . There was a significant inverse correlation between the magnitude of the change in nighttime BP and the night/day ratio . These results suggested that perindopril could induce a sustained decrease of the 24-h BP in patients with lacunar infa rct ion . In particular , a more pronounced nighttime BP-lowering effect was observed in non-dippers . As the incidence of non-dippers is reported to be high among patients with cerebrovascular disease , better nighttime BP control by perindopril might have helped to improve the outcome of such patients in PROGRESS Our objective was to compare three different methods of blood pressure measurement through the results of a controlled study aim ed at comparing the antihypertensive effects of tr and olapril and losartan . Two hundred and twenty-nine hypertensive patients were r and omized in a double-blind parallel group study . After a 3-week placebo period , they received either 2 mg tr and olapril or 50 mg losartan once daily for 6 weeks . At the end of both placebo and active treatment periods , three methods of blood pressure measurement were used : a ) office blood pressure ( three consecutive measurements ) ; b ) home self blood pressure measurements ( SBPM ) , consisting of three consecutive measurements performed at home in the morning and in the evening for 7 consecutive days ; and c ) ambulatory blood pressure measurements ( ABPM ) , 24-h BP recordings with three measurements per hour . Of the 229 patients , 199 ( 87 % ) performed at least 12 valid SBPM measurements during both placebo and treatment periods , whereas only 160 ( 70 % ) performed good quality 24-h ABPM recordings during both periods ( P < .0001 ) . One hundred-forty patients performed the three methods of measurement well . At baseline and with treatment , agreement between office measurements and ABPM or SBPM was weak . Conversely , there was a good agreement between ABPM and SBPM . The mean difference ( SBP/DBP ) between ABPM and SBPM was 4.6 + /- 10.4/3.5 + /- 7.1 at baseline and 3.5 + /- 10.0/4.0 + /- 7.0 at the end of the treatment period . The correlation between SBPM and ABPM expressed by the r coefficient and the P values were the following : at baseline 0.79/0.70 ( < 0.001/ < .0001 ) , with active treatment 0.74/0.69 ( 0.0001/.0001 ) . Hourly and 24-h reproducibility of blood pressure response was quantified by the st and ard deviation of BP response . Compared with office blood pressure , both global and hourly SBPM responses exhibited a lower st and ard deviation . Hourly reproducibility of SBPM response ( 10.8 mm Hg/6.9 mm Hg ) was lower than hourly reproducibility of ABPM response ( 15.6 mm Hg/11.9 mm Hg ) . In conclusion , SBPM was easier to perform than ABPM . There was a good agreement between these two methods whereas concordance between SBPM or ABPM and office measurements was weak . As hourly reproducibility of SBPM response is better than reproducibility of both hourly ABPM and office BP response , SBPM seems to be the most appropriate method for evaluating residual antihypertensive effect BACKGROUND Nilvadipine may lower rates of conversion from mild-cognitive impairment to Alzheimer 's disease ( AD ) , in hypertensive patients . However , it remains to be determined whether treatment with nilvadipine is safe in AD patients , given the higher incidence of orthostatic hypotension ( OH ) in this population , who may be more likely to suffer from symptoms associated with the further exaggeration of a drop in BP . OBJECTIVE The aim of this study was to investigate the safety and tolerability of nilvadipine in AD patients . METHODS AD patients in the intervention group ( n = 56 ) received nilvadipine 8 mg daily over 6-weeks , compared to the control group ( n = 30 ) who received no intervention . Differences in systolic ( SBP ) and diastolic ( DBP ) blood pressure , before and after intervention , was assessed using automated sphygmomanometer readings and ambulatory BP monitors ( ABP ) , and change in OH using a finometer . Reporting of adverse events was monitored throughout the study . RESULTS There was a significant reduction in the SBP of treated patients compared to non-treated patients but no significant change in DBP . Individuals with higher initial blood pressure ( BP ) had greater reduction in BP but individuals with normal BP did not experience much change in their BP . While OH was present in 84 % of the patients , there was no further drop in BP recorded on active st and studies . There were no significant differences in adverse event reporting between groups . CONCLUSION Nilvadipine was well tolerated by patients with AD . This study supports further investigation of its efficacy as a potential treatment for AD ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology This cross-sectional analysis of a population -based cohort investigates the postural changes in blood pressure ( BP ) and heart rate and assesses the prevalence of orthostatic hypotension ( OH ) and its associations with the medicines used by an elderly population . The study population ( n=1000 ) was a r and om sample of persons aged 75 years or older in the City of Kuopio , Finl and . In 2004 , altogether , 781 persons participated in the study . After the exclusion of persons living in institutional care ( n=82 ) and those without orthostatic test ( n=46 ) , the final study population comprised 653 home-dwelling elderly persons . OH was defined as a ⩾20 mm Hg drop of systolic BP or a ⩾10 mm Hg drop of diastolic BP or both 1 or 3 min after st and ing up from supine position . Systolic BP dropped for more than half of the home-dwelling elderly when they stood up from a supine to a st and ing position . The total prevalence of OH was 34 % ( n=220 ) . No significant gender or age differences were seen . The prevalence of OH was related to the total number of medicines in regular use ( P<0.05 ) . OH and postural changes in BP are more common among the home-dwelling elderly than reported in previous studies . The prevalence of OH is related to the number of medicines in regular use . There is an obvious need to measure orthostatic BP of elderly persons , as low BP and OH are important risk factors especially among the frail elderly persons |
2,145 | 28,508,107 | Conclusions Memantine add-on treatment may be beneficial for treating psychopathological symptoms ( especially negative symptoms ) in schizophrenia patients .
The negative-symptom effect size may be associated with younger adult schizophrenia patients | Rationale We examined whether memantine add-on to antipsychotic treatment is beneficial in schizophrenia treatment .
Objective This systematic review and meta- analysis aim ed to achieve stronger evidence on the efficacy and safety of memantine add-on for treating schizophrenia . | Background : Schizophrenia has been associated with disturbances of thalamic functioning . In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia , we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-d-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity . Methods : Based on the ketamine model of psychosis , we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan . Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind , r and omized , placebo-controlled , crossover design . Results : Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network , more precisely , an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex . Conclusions : Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage . This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists Background Dysfunction of neuroplasticity due to N-methyl-d-aspartate ( NMDA ) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia . Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms . Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study . We evaluate effects of memantine add-on treatment to clozapine for memory and executive function , and negative and positive symptoms in schizophrenia . Method Clozapine-treated patients with refractory schizophrenia were r and omly assigned to 12 weeks of double-blind adjunctive treatment with memantine ( n = 26 ) or placebo ( n = 26 ) . Crossover occurred after a 2-week placebo wash-out period . Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) , Positive and Negative Syndrome Scale ( PANSS ) , and Clinical Global Impression Severity Scale ( CGI-S ) . Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale . Results When compared with placebo , memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB ( effect size = 0.30 ) and PANSS negative subscale score ( effect size = 0.29 ) . Side effects were mild and transient . Conclusions In patients with clozapine-treated refractory schizophrenia , memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects . These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia The " glutamate hypothesis of schizophrenia " has changed attitudes in the development of new medications . This study aim ed to evaluate the effects of 20 mg of memantine per day ( as a NMDA receptor antagonist ) added to risperidone among male patients with schizophrenia . In a r and omized placebo-controlled , double-blind clinical trial , 46 adult male patients with schizophrenia were evaluated in both intervention and control groups at weeks 0 , 6 and 12 . The positive and negative symptoms scale and the mini mental status examination were used to assess positive , negative and cognitive symptoms and general psychopathology . The mean age of the patients was 44.8 for the intervention group and 45.3 for the control group , and the mean times since diagnosis were 23.5 and 25.7 years in the intervention and the control group , respectively . Positive and general psychopathologic symptoms showed no significant differences between the two groups at baseline or after treatment ; while negative symptoms improved significantly in the intervention group at week 12 . Cognitive function was also significantly improved in the intervention group at weeks 6 and 12 . Memantine is supported as an effective adjunct treatment to improve negative and cognitive symptoms in patients with schizophrenia Rationale Pro-cognitive agents for chronic psychotic disorders ( CPDs ) might be detected via experimental medicine models , in which neural targets engaged by the drug predict sensitivity to the drug ’s pro-cognitive effects . Objective This study aims to use an experimental medicine model to test the hypothesis that “ target engagement ” predicts pro-cognitive effects of the NMDA antagonist , memantine ( MEM ) , in CPDs . Methods MATRICS Consensus Cognitive Battery ( MCCB ) performance was assessed in CPD ( n = 41 ) and healthy subjects ( HS ; n = 41 ) in a double-blind , r and omized cross-over design of acute ( single dose ) MEM ( placebo vs. 10 or 20 mg p.o . ) . Measures of prepulse inhibition ( PPI ) and mismatch negativity previously reported from this cohort substantiated target engagement . Biomarkers predicting MEM neurocognitive sensitivity were assessed . Results Testing confirmed MCCB deficits associated with CPD diagnosis , age , and anticholinergic exposure . MEM ( 20 mg p.o . ) reduced MCCB performance in HS . To control for significant test order effects , an “ order-corrected MEM effect ” ( OCME ) was calculated . In CPD subjects , greater age , positive MEM effects on PPI , and SNP rs1337697 ( within the ionotropic NMDA receptor gene , GRIN3A ) predicted greater positive OCME with 20 mg MEM . Conclusions An experimental medicine model to assess acute pro-cognitive drug effects in CPD subjects is feasible but not without challenges . A single MEM 20 mg dose had a negative impact on neurocognition among HS . In CPD patients , age , MEM effects on PPI , and rs1337697 predicted sensitivity to the neurocognitive effects of MEM . Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients can not be inferred without a validating clinical trial BACKGROUND Glutamate deregulation may be involved in the neuropathology of schizophrenia , mainly through N-methyl-d-aspartate ( NMDA ) receptor dysfunction . Memantine , a drug approved by the FDA for the treatment of moderate to severe Alzheimer 's disease , acts as a weak nonselective NMDA receptor antagonist . The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia . METHOD In this double-blind , placebo-controlled study , out patients with refractory schizophrenia according to DSM-IV clinical criteria were r and omly assigned , from March 2005 to February 2008 , to receive either 20 mg/d memantine ( n = 10 ) or placebo ( n = 11 ) , in addition to clozapine , for 12 weeks . The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale ( BPRS ) and BPRS subscales of positive and negative symptoms . Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale ( CGI ) , cognition as assessed by the Mini-Mental State Examination ( MMSE ) , and extrapyramidal symptoms as assessed by the Simpson-Angus Scale ( SAS ) . RESULTS Twenty-one participants completed the study and were used in the analysis . Significant improvement ( P < .01 ) on the total BPRS score , its subscales of positive ( effect size [ ES ] = -1.38 ) and negative ( ES = -3.33 ) symptoms , the CGI score ( ES = 1.56 ) , and the MMSE score was observed with memantine as compared with placebo . No significant changes in extrapyramidal symptoms were observed . CONCLUSIONS Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00757978 Glutamate dysregulation may be involved in the neuropathology of schizophrenia . Memantine , a drug approved by the FDA for the treatment of moderate to severe Alzheimer 's disease , acts as a partial uncompetitive NMDA receptor antagonist . The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to olanzapine in patients with schizophrenia . In this double-blind , placebo-controlled studies , patients with schizophrenia according to DSM-IV clinical criteria were selected . Patients were r and omly assigned to receive either memantine ( week 1:10 mg/day ; weeks 2 - 6:20 mg/day ) plus olanzapine ( 15 - 20 mg/day ) or olanzapine plus placebo . At baseline , no statistically significant difference regarding the mean total PANSS scores between treatment groups was found . Results showed that memantine significantly improved the positive and negative PANSS score in patients maintained on olanzapine after six weeks compared to olanzapine alone ( P<0.001 ) . Furthermore , female patients showed significantly better response than males , especially in positive PANSS score . No significant changes in extrapyramidal symptoms were observed . These findings indicate that olanzapine efficacy might be augmented with memantine . Furthermore , this effect is more remarkable in female patients with schizophrenia Background : Schizophrenia severely influences function and quality of life . The benefit of newer antipsychotics in improving the quality of life in schizophrenia still remains controversial . The aim of the present study is to evaluate the effect of memantine on global function and quality of life in patients with schizophrenia . Material s and Methods : This was a r and omized controlled trial on inpatient cases of schizophrenia in Noor University Hospital , Isfahan , Iran . A number of 64 patients were selected through sequential sampling ; patients were r and omly allocated in intervention and placebo groups . The intervention group was treated with memantine plus previously administered , stabled-dose , atypical antipsychotic , while the control group received placebo plus previously administered , stabled-dose , atypical antipsychotic . Memantine administration was initiated at 5 mg daily ; the dosage was increased at weekly intervals by 5 mg and finally up-titrated to 20 mg daily within 4 weeks . All patients were assessed by means of Global Assessment of Functioning ( GAF ) and quality of life scale ( QLS ) initially and every four weeks to the end of the 12th week . Results : Analysis of baseline GAF and QLS scores showed no significant differences between the two groups ( P = 0.081 and P = 0.225 , respectively ) . GAF and QLS scores increased in both groups ; but it was higher in the intervention group . The difference between the two groups was statistically significant . ( P < 0.001 and P < 0.001 , respectively ) memantine was well tolerated , with no significant side effects . Conclusion : Add-on memantine was significantly effective in improving the global function of patients as well as their quality of life Abstract We aim ed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia . In a double-blind placebo-controlled clinical trial , 40 patients with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ) who were stabilized on risperidone for a minimum of 8 weeks were r and omized to either memantine ( 20 mg ) or placebo in addition to risperidone , 6 mg/d , for eight weeks . Assessment was done using the Positive and Negative Syndrome Scale at baseline , week 4 , and week 8 . The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms , respectively . All 40 patients had at least one postbaseline measurement , and 38 patients completed the trial . Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point ( P < 0.001 ) . The same effect was observed for the total score ( P < 0.001 ) and the general psychopathology subscale score ( P = 0.002 ) . There was no significant difference in reduction of positive symptoms score between the 2 groups ( P = 0.757 ) . Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups . Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia |
2,146 | 20,024,751 | We discerned congruence between the prominence of substance abuse as a factor identified in the descriptive studies as a barrier to adherence and its prominence as the problem most addressed in those reports of intervention studies that specified the problems targeted for intervention .
We also discerned congruence between the prominence of family and provider support as factors identified in the descriptive studies as facilitators of adherence and the presence of social support as an intervention component and outcome variable .
Less discernible in the reports of intervention studies was specific attention to other factors prominent in the descriptive studies , which may be due to the complex nature of the problem , individualistic and rationalist slant of interventions , or simply the ways interventions were presented . | Abstract We examined the extent to which studies aim ed at testing interventions to improve antiretroviral adherence have targeted the facilitators of and barriers known to affect adherence . | Optimists ( people who have positive expectations about the future ) have been shown to perform more health-promoting behaviors than pessimists . This study attempts to alter individuals ’ levels of optimism , and thereby their health behaviors , by having them write about a positive future . HIV-infected women ( N = 40 ) on combination therapies were r and omly assigned to write about a positive future or assigned to a no-writing control group . Among participants who were low in optimism , the writing intervention led to increased optimism , a trend toward increased self-reported adherence to medications , and decreased distress from medication side effects , compared to controls who did not write . Participants who were high in optimism showed the opposite effects after writing about the future . Results suggest that a future-oriented writing intervention may be a promising technique to increase medication adherence and decrease symptom , distress in pessimistic individuals Background : We prospect ively studied the impact of an adherence counselor on the outcome of patients failing antiretroviral therapy because of nonadherence . Methods : Forty-six patients , identified as chronically nonadherent were enrolled . Individual attention was provided using the information , motivation and behavioral methodology . HIV RNA ( viral load , in copies/mL ) , CD4 count ( in cells/mm 3 ) , and body weight before and after the adherence counselor were measured . Qualitative outcome and patient satisfaction were assessed by deidentified third-party interviews . Results : Over half completed at least 1 year ; only 8 patients were lost to follow-up . Mean CD4 counts increased significantly ( P < .05 ) for completers at 6 and 12 months . Viral loads decreased between baseline and 6 months . Most clients reported subjective benefit from working with the adherence counselor . Conclusion : Although few clients showed complete virologic suppression , the value of an adherence counselor was vali date d. Longer term adherence programs should be evaluated A r and omized 2-group medication adherence intervention is evaluated with HIV-infected adults ( N = 141 ) assessed at baseline , 3- , and 9-month follow-ups . Cognitive ( self-efficacy , behavioral intent ) , mental health ( depression , well-being ) , and substance use indicators were the outcome measures . In addition , a posttest-only analysis from 3 to 9 months evaluates intervention impact on antiretroviral adherence , measured through Medication Event Monitoring System and pill counts . Compared to the st and ard care group , the intervention group showed significant increases in adherence self-efficacy and behavioral intent at 3 and 9 months and marginal improvements in mental health . Although the st and ard care group had higher adherence at 3 months ( no baseline data were available prior to intervention ) , intervention group patients showed significant increases in adherence from 3 to 9 months . Although adherence levels achieved by intervention patients may not be sufficient for virological control , this is one of the first studies to provide promising results of longer term effectiveness of a behavioral adherence intervention The impact of an adherence enhancement program for low income HIV-infected Spanish-speaking Latinos on health literacy , patient-provider relationships , and adherence to HAART was examined . Evaluations were conducted at baseline , 6 weeks , and 6 months for participants ( n = 85 ) r and omly assigned to either the intervention group or a comparison group ; 69 ( 81 % ) remained in the study for the entire 6-month duration . The intervention group scored significantly better than the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on 2 of 5 measures , at 6 months . While there was a weak trend for the intervention group to report an increase in self-efficacy of medication adherence management , baseline to 6 weeks , no other changes were significant . Perceptions of the quality of relationship and communications with their HIV-treating physicians improved both at 6 weeks ( p = 0.04 ) and at 6 months ( p < 0.001 ) . The comparison group showed little change baseline to 6 weeks and baseline to 6 months . While there was a trend for the pilot group to report better medication adherence , these differences were not statistically significant . Further evaluation of the impact of this adherence enhancement program is needed Child sexual abuse ( CSA ) is associated with HIV risk behaviors [ Bensley , L. , Van Eenwyk , J. , and Simmons , K. W. , 2003 . ] and more prevalent among women living with HIV than in the general population [ Koenig , L. J. , and Clark , H. , 2004 ] . This r and omized Phase ~ I clinical trial tested the impact of a culturally congruent psychoeducational intervention design ed to reduce sexual risks and increase HIV medication adherence for HIV-positive women with CSA histories . An ethnically diverse sample of 147 women were r and omized to two conditions : an 11-session Enhanced Sexual Health Intervention ( ESHI ) or an attention control . Results based on “ intent to treat ’ ’ analysesof pre – post changes are reported here . Additional analyses explored whether theobserved effects might depend on “ intervention dose , ’ ’ i.e. , number of sessions attended . Women in the ESHI condition reported greater sexual risk reduction than women in the control condition . Although there were no differences between women in the ESHI and control groups on medication adherence , women in the ESHI condition who attended 8 or more sessions reported greater medication adherence at posttest than control women . The findings provide initial support for this culturally and gender-congruent psychoeducational intervention for HIV-positive women with CSA , and highlight the importance of addressing the effects of CSA on sexual risk reduction and medicationadherence in preventive interventions for women This study r and omized 90 HIV-seropositive , methadone-maintained injection drug users ( IDUs ) to an HIV Harm Reduction Program ( HHRP+ ) or to an active control that included harm reduction components recommended by the National AIDS Demonstration Research Project . The treatment phase lasted 6 months , with follow-ups at 6 and 9 months after treatment entry . Patients in both treatments showed reductions in risk behaviors . However , patients assigned to HHRP+ were less likely to use illicit opiates and were more likely to adhere to antiretroviral medications during treatment ; at follow-up , they had lower addiction severity scores and were less likely to have engaged in high risk behavior . Findings suggest that enhancing methadone maintenance with an intervention targeting HIV-seropositive IDUs increases both harm reduction and health promotion behaviors This study examined whether a self-management intervention based on feedback of adherence performance and principles of social cognitive theory improves adherence to antiretroviral dosing schedules . Forty-three individuals with HIV/AIDS who were starting or switching to a new protease inhibitor regimen were r and omly assigned to be in a medication self-management program or usual care control group . The self-management program included skills development exercises , three monthly visits for medication consultations , and monthly feedback of adherence performance using electronic monitors on medication bottles . Participants also completed a 40-item question naire that measured self-efficacy to take medications , on schedule , in a variety of situations . Logistic regression analysis indicated that individuals in the self-management group were significantly more likely to take 80 % or more of their doses each week than individuals in the control group ( n=29 , OR=7.8 , 95 % CI=2.2 - 28.1 ) . Self-management training with feedback of adherence performance is a potentially useful model for improving adherence to complex regimens in HIV/AIDS care Background . Patients cite " forgetting " as a reason for nonadherence to highly active antiretroviral therapy ( HAART ) . We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects . Methods . The study was a prospect i ve , r and omized , controlled trial involving 64 HIV-infected adults . The intervention was the Disease Management Assistance System ( DMAS ) device , combined with monthly adherence counseling . Control subjects received only adherence counseling . The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times . Adherence was measured for 24 weeks using electronic drug exposure monitor ( eDEM ) caps . Results . A total of 58 subjects completed the 24-week study period ; 28 were HAART naive ( 12 DMAS users and 16 control subjects ) . Mean adherence scores did not differ significantly between DMAS users ( 80 % ) and control subjects ( 65 % ) . Post hoc analysis of 31 memory-impaired subjects ( 14 DMAS users and 17 control subjects ) revealed significantly higher adherence rates among DMAS users ( 77 % ) , compared with control subjects ( 57 % ) ( P=.001 ) . However , analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users ( 83 % ) , compared with control subjects ( 77 % ) ( P=.25 ) . At week twelve , 38 % of the DMAS users and 14 % of the control subjects had an undetectable plasma HIV RNA load ( P=.014 ) , and at week 24 , the plasma HIV RNA load was undetectable for 34 % of the DMAS users and 38 % of the control subjects ( P=.49 ) . CD4(+ ) cell counts did not differ between the study arms . Virological and immunological responses were not related to DMAS use in memory-impaired subjects . Conclusion . The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects BACKGROUND Directly administered antiretroviral therapy ( DAART ) in methadone clinics has the potential to improve treatment outcomes for human immunodeficiency virus (HIV)-infected injection drug users ( IDUs ) . METHODS DAART was provided at 3 urban methadone clinics . Eighty-two participants who were initiating or reinitiating highly active antiretroviral therapy ( HAART ) received supervised doses of therapy at the clinic on the mornings on which they received methadone . Treatment outcomes in the DAART group were compared with outcomes in 3 groups of concurrent comparison patients , who were drawn from the Johns Hopkins HIV Cohort . The concurrent comparison patients were taking HAART on a self-administered basis . The 3 groups of concurrent comparison patients were as follows : patients with a history of IDU who were receiving methadone at the time HAART was used ( the IDU-methadone group ; 75 patients ) , patients with a history of IDU who were not receiving methadone at the time that HAART was used ( the IDU-nonmethadone group ; 244 patients ) , and patients with no history of IDU ( the non-IDU group ; 490 patients ) . RESULTS At 12 months , 56 % of DAART participants achieved an HIV type 1 RNA level < 400 copies/mL , compared with 32 % of participants in the IDU-methadone group ( P=.009 ) , 33 % of those in the IDU-nonmethadone group ( P=.001 ) , and 44 % of those in the non-IDU group ( P=.077 ) . The DAART group experienced a median increase in the CD4 cell count of 74 cells/mm3 , compared with 21 cells/mm3 in the IDU-methadone group ( P=.04 ) , 33 cells/mm3 in the IDU-nonmethadone group ( P=.09 ) , and 84 cells/mm3 in the non-IDU group ( P=.98 ) . After adjustment for other covariates in a logistic regression model , DAART participants were significantly more likely to achieve viral suppression than were patients in each of the 3 comparison groups . CONCLUSIONS These results suggest that methadone clinic-based DAART has the potential to provide substantial clinical benefit for HIV-infected IDUs A 24-week open-label clinical trial was conducted in 195 HIV-infected adults commonly underrepresented in research ( 35 % female , 71 % African American , 21 % Hispanic , and 20 % injection drug users [ IDUs ] ) to evaluate the effect of an HIV educational program on efficacy and adherence with a simple , compact , twice-daily triple nucleoside regimen containing a lamivudine ( 150 mg)/zidovudine ( 300 mg ) combination ( COM ) tablet plus abacavir ( ABC ) , 300 mg . At baseline , the patients ' median plasma HIV-1 RNA level was 4.18 log10 copies/mL and the median CD4 + cell count was 379 cells/mm3 . Patients were r and omized 1:1 to 4 modules of the Tools for Health and Empowerment HIV education intervention plus routine counseling ( EI + RC ; n = 96 ) or to routine counseling alone ( RC ; n = 99 ) . No differences between the EI + RC and RC treatment arms were observed with respect to the proportion of patients achieving plasma HIV-1 RNA levels < 40 copies/mL ( 60 % [ 33/55 ] vs. 55 % [ 38/69 ] ; P = 0.529 ) or < 400 copies/mL ( 80 % [ 44/55 ] vs. 80 % [ 55/69 ] ; P = 0.689 ) at week 24 ( intent-to-treat observed analysis ) , increase in median CD4 cell count above baseline at week 24 ( 78.3 vs. 104.8 cells/mm3 ; P = 0.498 ) , or mean overall adherence rates as measured by the Medication Event Monitoring System ( MEMS ) ( 70 % vs. 74 % ) . COM + ABC was generally well tolerated , and no association was observed between interruptions in treatment and the development of ABC hypersensitivity ( 5 suspected cases ) . In conclusion , in underrepresented patients , the EI used in this study did not affect the efficacy and adherence results with ABC + COM to any greater degree than did RC Antiretroviral therapy ( ART ) is effective in controlling viral load in many people infected with HIV , but high levels of adherence to ART are needed for prolonged viral suppression . This study evaluated a brief adherence intervention delivered to HIV-positive patients by primary care providers during routine medical examinations . Six clinics were r and omly allocated to deliver an intervention focusing on ART adherence ( 2 clinics ) or safer sex ( 4 clinics ) . Interventions included written information ( posters , brochures , and flyers ) and brief counseling from providers and were evaluated with cohorts of r and omly selected patients ( n = 437 ) measured before and after a 10-month intervention . Among those 95 % or greater adherent at baseline , 91 % of patients who received the adherence intervention remained 95 % or greater adherent at follow-up compared with 75 % of the patients who received the safer sex intervention ( χ2 = 12.59 , P < 0.01 ) . This difference was significant in a logistic regression analysis ( odds ratio = 2.26 ; 95 % confidence interval = 1.27 - 4.04 ) , adjusting for baseline adherence , demographics , and HIV medical status . The adherence intervention did not significantly increase the prevalence of 95 % or greater adherence among patients less than 95 % adherent at baseline . Similar but nonsignificant results were observed for viral load . A brief intervention delivered to HIV patients by their primary providers helped to maintain adequate adherence to ART regimens . More intensive intervention is needed to improve adherence among patients who are initially less than 95 % adherent This report describes a pilot study of a nursing intervention to increase adherence to combination therapy . The intervention was based on motivational interviewing ( MI ) . Participants completed a baseline assessment using the computer-administered self-interview with audio ( ACASI ) data collection method and then were r and omly assigned to the MI intervention or control condition . Nurse counselors met with participants in the MI intervention group for three adherence sessions . Two months following baseline , participants completed a follow-up assessment . Mean scores on ratings of missed medications were lower for participants in the intervention group than those in the control group . Although there were no significant differences in the number of medications missed during the past 4 days , participants in the MI group reported being more likely to follow the medication regimen as prescribed by their health care provider . The pilot study provided useful information about the acceptability of ACASI and the adequacy of intervention procedures . The results of this pilot study show promise for the use of MI as an intervention to promote adherence to antiretroviral medications Objective : To evaluate the efficacy of a program design ed to improve adherence to antiretroviral therapy among patients with poor adherence . Methods : A r and omized intervention trial was conducted among 90 HIV-positive patients experiencing treatment failure as a result of noncompliance with their medication regimen . Eligible participants were r and omly assigned to an adherence case management intervention with monetary reinforcement ( CM ) or to a st and ard of care group ( SC ) . The CM participants met regularly with a treatment advocate for individualized adherence support . Efficacy was measured in terms of reductions in viral load and improvements in immune function at weeks 12 , 24 , and 48 . Results : After 48 weeks , 55 % ( n = 26 ) of those in the CM achieved at least a 1-log10 drop in viral load as compared to 28 % ( n = 12 ) in the SC group ( P = .0089 ) . Furthermore , the mean CD4 count was 209 cells/mm3 for the CM group as compared to 150 cells/mm3 in the SC group ( P = .0333 ) . Based on logistic regression analysis , being in the CM was an independent predictor of reduction in viral load ( odds ratio = 2.49 ; P = .0514 ) . Conclusion : The individualized adherence intervention is feasible and effective in reducing viral load and improving immune function Abstract Directly administered antiretroviral therapy ( DAART ) is an intensive adherence support strategy for highly active antiretroviral therapy ( HAART ) that requires patient acceptance to be effective . In one arm of a r and omized adherence study , community workers ( CW ) delivered and observed ingestion of one HAART dose to participants five days a week for six months . We evaluated acceptability by study participation , retention , attendance and a satisfaction survey . Chi-square and nonparametric tests were used to examine differences between participants who did and did not complete DAART . Between November 2001 and March 2004 , 416 eligible participants were identified ; 250 were enrolled and 166 refused to participate ( 22 of these ( 13 % ) because of DAART specifically ) . Of the 82 r and omized to DAART ( 70 % Latino , 20 % African American , 27 % female and 69 % foreign-born ) , 65 ( 79 % ) completed six months of DAART . Participants attended 6,953/7,390 ( 94 % ) appointments . Latinos were more likely to complete DAART compared to African Americans ( OR=4.76 , 95%CI=1.38 , 16.44 , p=0.01 ) . In addition , foreign-born participants were more likely to complete DAART than US-born participants ( OR=3.38 , 95%CI=1.11–10.22 , p=0.03 ) . Participants completing DAART reported high rates of satisfaction . Retention , attendance and participant satisfaction suggest that DAART is an acceptable adherence support strategy in this public clinic population , particularly among Latino and foreign-born participants OBJECTIVE To assess the feasibility and efficacy of two interventions for improving adherence to antiretroviral therapy regimens in HIV-infected subjects compared with a control intervention . DESIGN R and omized , controlled , pilot study . SETTING Department of Veterans Affairs HIV clinic and community-based HIV clinical trials site . PARTICIPANTS Fifty-five HIV-infected subjects on stable antiretroviral therapy regimens . Subjects were predominantly male ( 89 % ) and African American ( 69 % ) , and had histories of heroin or cocaine use ( 80 % ) . INTERVENTIONS Four weekly sessions of either nondirective inquiries about adherence ( control group , C ) , cue-dose training , which consisted of the use of personalized cues for remembering particular dose times , and feedback about medication taking using Medication Event Monitoring System ( MEMS ) pill bottle caps , which record time of bottle opening ( CD group ) , or cue-dose training combined with cash reinforcement for correctly timed bottle opening ( CD+CR ) . MEASUREMENTS Opening of the pill bottle within 2 hours before or after a predetermined time was measured by MEMS . RESULTS Adherence to the medication as documented by MEMS was significantly enhanced during the 4-week training period in the CD+CR group , but not in the CD group , compared with the control group . Improvement was also seen in adherence to antiretroviral drugs that were not the object of training and reinforcement . Eight weeks after training and reinforcement were discontinued , adherence in the cash-reinforced group returned to near-baseline levels . CONCLUSIONS Cue-dose training with cash reinforcement led to transient improvement in adherence to antiretroviral therapy in a population including mostly African Americans and subjects with histories of drug abuse . However , we were not able to detect any sustained improvement beyond the active training period , and questions concerning the timing and duration of such an intervention require further study . R and omized , controlled clinical studies with objective measures of adherence can be conducted in HIV-infected subjects and should be employed for further evaluation of this and other adherence interventions Contingency management ( CM ) based interventions that reinforce adherence to prescribed medications have shown promise in a variety of disadvantaged population s. Fifty-six participants with histories of illicit substance use who were prescribed antiretroviral medication but evidence d suboptimal adherence during a baseline assessment were r and omly assigned to 16 weeks of weekly CM-based counseling or supportive counseling , followed by 16 additional weeks of data collection and adherence feedback to providers . The CM intervention involved review of data generated by electronic pill-bottle caps that record bottle opening ( MEMS ) and brief substance abuse counseling . CM participants were reinforced for MEMS-measured adherence with drawings from a bowl for prizes and bonus drawings for consecutive weeks of perfect adherence . Potential total earnings averaged $ 800 . Mean MEMS-measured adherence to the reinforced medication increased from 61 % at baseline to 76 % during the 16-week treatment phase and was significantly increased relative to the supportive counseling group ( p = 0.01 ) . Furthermore , mean log-transformed viral load was significantly lower in the CM group . However , by the end of the 16-week follow-up phase , differences between groups in adherence and viral load were no longer significantly different . Proportions of positive urine toxicology tests did not differ significantly between the two groups at any phase . A brief CM-based intervention was associated with significantly higher adherence and lower viral loads . Future studies should evaluate methods to extend effects for longer term benefits Objective : To assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems . Design : A r and omized controlled trial ( SMART Couples Study ) conducted between August 2000 and January 2004 . Setting : Two HIV/AIDS outpatient clinics in New York City . Participants : Heterosexual and homosexual HIV-serodiscordant couples ( n = 215 ) in which the HIV-seropositive partner had < 80 % adherence at baseline . The sample was predominantly lower-income racial/ethnic minorities . Intervention : Participants were r and omly assigned to a four-session couple-focused adherence intervention or usual care . The intervention consisted of education about treatment and adherence , identifying adherence barriers , developing communication and problem-solving strategies , optimizing partner support , and building confidence for optimal adherence . Outcome measures : Medication adherence at week 8 ( 2 weeks after the intervention ) compared with baseline , assessed with a Medication Event Monitoring System cap . Results : Intervention participants showed higher mean medication adherence at post-intervention when compared with controls whether adherence was defined as proportion of prescribed doses taken ( 76 % versus 60 % ) or doses taken within specified time parameters ( 58 % versus 35 % ) . Also , participants in the intervention arm were significantly more likely to achieve high levels of adherence ( > 80 % , > 90 % , or > 95 % ) when compared with controls . However , in most cases , effects diminished with time , as seen at follow-up at 3 and 6 months . Conclusion : The SMART Couples program significantly improved medication adherence over usual care , although the level of improved adherence , for many participants , was still suboptimal and the effect was attenuated over time BACKGROUND A r and omized , controlled trial was conducted to evaluate the impact of a directly administered antiretroviral therapy program ( DAART ) and intensive adherence case management ( IACM ) intervention on virologic and immunologic response to highly active antiretroviral therapy ( HAART ) among patients at 3 public human immunodeficiency virus clinics in Los Angeles County , California . METHODS Participants included 250 treatment-naive and treatment-experienced persons for whom no more than 1 prior HAART regimen had failed . Five days per week for 6 months , a community worker delivered 1 HAART dose to DAART participants and observed the participant take it . IACM participants met weekly with a case manager to overcome barriers to HAART adherence . A control group ( the st and ard of care [ SOC ] group ) received the usual care . RESULTS The majority of patients were Latino ( 64 % ) or African American ( 24 % ) ; 57 % were monolingual Spanish speakers . Seventy-five percent of the patients were male , and 64 % reported an annual income of < 10,000 dollars . In an intent-to-treat analysis , no statistical differences were observed in the percentage of patients with an undetectable viral load ( i.e. , < 400 copies/mL ) at 6 months between the DAART group ( 54 % ) , IACM group ( 60 % ) , and SOC group ( 54 % ; P>.05 ) . An on-treatment analysis determined that there were no statistical differences in the percentage of patients with an undetectable viral load at 6 months between the DAART group ( 71 % ) , IACM group ( 80 % ) , and SOC group ( 74 % ; P>.05 ) . Additionally , there were no statistical differences in 6-month changes in the CD4 + cell count or in self-reported adherence to therapy . CONCLUSIONS Among patients with limited prior HAART experience and adherence barriers that had not been assessed before r and omization , no differences were found in virologic or immunologic response for DAART or IACM , compared with SOC , at 6 months . DAART and IACM did not improve short-term outcomes when SOC included other means of adherence support that were not controlled for by the study design OBJECTIVE To assess the effectiveness of an individualized multicomponent intervention to promote adherence to antiretroviral therapy ( ART ) in a cohort of HIV-infected individuals with a history of alcohol problems . DESIGN We conducted a r and omized controlled trial to compare the usual medical follow-up with an adherence intervention . SETTING The principal enrolment site was Boston Medical Center , a private , not-for-profit , academic medical institution . SUBJECTS HIV-infected patients with a history of alcohol problems on ART . A total of 151 were enrolled and 141 ( 93 % ) were assessed at follow-up . INTERVENTION A nurse , trained in motivational interviewing , completed the following over 3 months in four encounters : addressed alcohol problems ; provided a watch with a programmable timer to facilitate pill taking ; enhanced perception of treatment efficacy ; and delivered individually tailored assistance to facilitate medication use . MAIN OUTCOME MEASURES Prior 30-day adherence > or = 95 % , prior 3-day adherence of 100 % , CD4 cell count , HIV RNA and alcohol consumption , each at both short- and long-term follow-up . RESULTS At follow-up , no significant differences in medication adherence , CD4 cell count , HIV RNA or alcohol consumption were found ( all P values > 0.25 ) . CONCLUSIONS A multicomponent intervention to enhance adherence among HIV-infected individuals with a history of alcohol problems was not associated with changes in medication adherence , alcohol consumption or markers of HIV disease progression . The failure to change adherence in a group at high risk for poor adherence , despite utilizing an intensive individual-focused patient intervention , supports the idea of addressing medication adherence with supervised medication delivery or markedly simplified dosing regimens Injection drug use is an important factor in the spread of HIV infection , and strategies to enhance adherence to HIV therapeutics are critically important to controlling viral transmission and improving clinical outcomes . To this end , the authors sought ( 1 ) to enhance adherence to highly active antiretroviral therapy ( HAART ) among methadone-maintained injection drug users ( IDUs ) using modified directly observed therapy ( MDOT ) , and ( 2 ) to define interactions between methadone and HAART and the potential contribution of drug interactions to adherence and HIV outcomes in this population . Adherence was explored here through a pilot , unblinded , 24-week study in a methadone maintenance program in which simplified HAART ( efavirenz and didanosine [ one daily ] and a second nucleoside [ twice daily ] ) was administered 6 days/week by clinic staff to HIV-infected IDUs ( n = 5 ) with their methadone . Evening doses of riboflavin-tagged nucleoside and one full day of medication weekly were given as take home doses . As a result of HAART administration , four of five participants with mean viral load at baseline of 10(5 ) copies/ml had undetectable viral load by 8 weeks of treatment ( p = .043 ) . Methadone area under the curve ( AUC ) decreased by 55 % ( p = .007 ) within 2 weeks of initiating this HAART regimen , and a mean methadone dose increase of 52 % was required . The authors conclude that MDOT is a promising intervention for the treatment of IDUs with HIV disease , though significant drug interactions must be monitored for carefully and rapidly addressed The purpose of the present study was to determine whether changes in self-efficacy over time would be related to changes in disease progression markers ( CD4 , viral load ) in a sample of women with AIDS . A self-efficacy measure was developed and two sub-scales emerged via factor analysis of 391 HIV-positive women : AIDS Self-efficacy and Cognitive Behavioral Skills Self-efficacy . Subsequently , the sub-scales and an additional adherence self-efficacy item were given to 56 HIV-positive women who were measured at two time points three months apart . Half of these women were r and omly assigned to a CB intervention and half to a low intensity comparison condition . Increases in AIDS Self-efficacy over the three-month period were significantly related to increases in CD4 and decreases in viral load . Similarly , increases in Cognitive Behavioral Skills Self-efficacy were significantly related to decreases in distress over time . Findings were maintained within the intervention group alone . Interestingly , increases in cognitive behavioral skills self-efficacy and increases in the self-efficacy adherence item were also significantly related to decreases in viral load . Implication s of the findings and suggestions for future research are discussed This clinical trial evaluated a contingency management intervention design ed to improve medication adherence among HIV-positive methadone maintenance patients . After a 4-week baseline observation phase , eligible participants ( N=66 ) were r and omly assigned to : ( a ) medication coaching sessions every other week to assist with adherence strategies ( comparison group ) or ( b ) medication coaching plus voucher reinforcement for opening electronic medication caps on time ( voucher group ) . Baseline adherence ( percent doses taken/percent total possible doses ) was 51 % using electronic measurement , 75 % using self-report and 75 % using pill count . The intervention was provided for 12 weeks , with a 4-week follow-up . The primary outcome results of the clinical trial indicated effectiveness during the intervention , with significant mean adherence differences between voucher and comparison groups using electronic measurement ( 78 % versus 56 % ) , pill count ( 86 % versus 75 % ) , and self-report ( 87 % versus 69 % ) . Differences between groups faded after vouchers were discontinued . Contingency management shows promise as a strategy to promote antiretroviral medication adherence in this population Background : Adherence interventions for HAART can impact challenging population s , such as active substance users . Community-based modified directly observed therapy ( MDOT ) is a promising approach that needs to be critically evaluated . Methods : This study was a r and omized clinical trial . HIV seropositive substance users were r and omized to either st and ard of care ( SOC ) or MDOT , stratified by HAART experience . All participants were placed on a once-daily regimen and were met by an outreach worker for all 7 days during the first 3 months . We used an intent-to-treat analysis to evaluate differences in viral load suppression [ > 2 log drop in plasma viral load ( PVL ) or PVL < 50 ] and changes in PVL and CD4 cell count from baseline to 3 months . Results : A total of 87 participants were enrolled ( 43 in SOC , 44 in MDOT ) , Using repeated measures logistic regression , MDOT participants were more likely to achieve PVL suppression ( odds ratio , 2.16 ; 95 % confidence interval , 1.0–4.7 ) , driven primarily by those HAART experienced ( odds ratio , 2.88 ; 95 % confidence interval , 1.2–7.0 ) . A significant treatment effect was also found in CD4 cell count change ( P < 0.05 ) . No differences were found by arm in undetectable PVL . Conclusion : This study provides evidence that MDOT is an effective strategy to reduce viral load and increase CD4 cell counts in HAART experienced substance users . MDOT should be included in the spectrum of options to enhance adherence in this population Adherence to antiretroviral therapy is critical for treatment success . Antiretroviral therapy typically requires multiple pills at multiple dosing times . To address this , we tested the feasibility , utility , and efficacy of a customizable reminder system using pagers , which were programmed using web-based technology , to increase and maintain proper adherence in patients with pre-existing adherence problems . After a two-week monitoring period with an electronic pill-cap , participants with less than 90 % adherence were r and omized to continue monitoring or to receive a pager . The group who received the pagers had greater improvements in adherence from baseline to Week 2 and Week 12 than those who monitored their medications only . However , adherence in both groups at the outcome assessment s points was still poor . While the provision of a reminder system helped improve adherence , it is likely that more intensive interventions are required for patients with pre-existing problems OBJECTIVE : To identify gender differences in social and behavioral factors associated with antiretroviral adherence . DESIGN : Prospect i ve cohort study . SETTING : Methadone maintenance program . PARTICIPANTS : One hundred thirteen HIV-seropositive current or former opioid users . MEASUREMENTS AND MAIN RESULTS : Participants were surveyed at baseline about social and behavioral characteristics and at monthly research visits about drug and alcohol use and medication side effects . Electronic monitors ( MEMS ) were used to measure antiretroviral adherence . Median adherence among women was 27 % lower than among men ( 46 % vs. 73 % ; P<.05 ) . In gender-stratified multivariate models , factors associated with worse adherence in men included not belonging to an HIV support group ( P<.0001 ) , crack/cocaine use ( P<.005 ) , and medication side effects ( P=.01 ) . Among women , alcohol use ( P=.005 ) , heroin use ( P<.05 ) , and significant medication side effects ( P<.005 ) were independently associated with worse adherence . In a model including both men and women , worse adherence was associated with lack of long-term housing ( P<.005 ) , not belonging to any HIV support groups ( P<.0005 ) , crack or cocaine use ( P<.01 ) , and medication side effects ( P<.0005 ) . In addition , worse adherence was associated with the interaction between female gender and alcohol use ( P ≤ .05 ) . CONCLUSIONS : In this cohort of current and former opioid users , gender-stratified analysis demonstrated that different social and behavioral factors are associated with adherence in men and women . Among both men and women , worse adherence was associated with lack of long-term housing , not belonging to an HIV support group , crack/cocaine use , and medication side effects . Among women only , alcohol use was associated with worse adherence Objectives : To examine the relationship between antiretroviral adherence and viral load , and to determine the predictors of adherence over time in HIV-infected women . Design : Prospect i ve observational study . Methods : One-hundred sixty-one HIV-infected women who were taking antiretroviral therapy for a median of 3.0 years were recruited from the HIV Epidemiology Research Study , a multicenter cohort study of HIV infection in women . Antiretroviral adherence ( percent of doses taken as prescribed ) was measured over a 6-month period using MEMS caps . At baseline and follow-up , CD4 lymphocyte count and viral load were measured , and a st and ardized interview was administered to elicit medication history and drug use behaviors . To examine changes in adherence over time , the mean adherence to all antiretroviral agents was calculated for each monitored month . Results : Adherence varied significantly over time ( P < 0.001 ) , ranging from a mean of 64 % in month 1 to 45 % in month 6 . Nearly one-fourth of the participants had a 10 % or greater decrease in adherence between consecutive months . Virologic failure occurred in 17 % of women with adherence of ⩾ 88 % , 28 % of those with 45–87 % adherence , 43 % of those with 13–44 % adherence , and 71 % of those with ⩽ 12 % adherence . In multivariate analysis , factors predicting lower adherence included active drug use , alcohol use , more frequent antiretroviral dosing , shorter duration of antiretroviral use , younger age , and lower initial CD4 lymphocyte count . Conclusions : Antiretroviral adherence is not stable over time . Interventions aim ed at monitoring and improving long-term adherence in women are urgently needed Long-term medication regimen adherence is challenging in all population s , but in the HIV-infected adolescent population the frequency of poverty , homelessness , substance abuse , and mental illness make highly active antiretroviral therapy ( HAART ) adherence even more challenging . In 2003 , we developed a pilot program for HIV-infected adolescents and young adults between the ages of 16 and 24 who were either going to begin a HAART regimen for the first time or begin a new HAART regimen . Participants received a free cell phone with a local service plan for approximately 6 months . Participants received phone call reminders for 12 weeks . Call frequency was tapered at 4-week intervals . Patients were assessed at 4-week intervals to determine the perceived intrusiveness or helpfulness of receiving calls , and missed medication doses . Eight consecutive patients were recruited for the study , and five were able to complete it through the 24 weeks . Most participants found the calls to be helpful and the level of intrusion into their daily lives acceptable . Using cell phone reminders to assist patients does not require an extensive amount of daily staff time . Tapering calls rapidly over 3 months , followed by discontinuation of calls provided inadequate support for subjects , especially those with significant psychosocial issues such as substance abuse . Use of cell phone reminders to assist adolescents adhere with HIV medications was practical and acceptable to pilot study participants . Viral suppression waned for all but two patients after termination of cell phone reminders and suggests that a 12-week intervention was not adequate for most subjects . Larger prospect i ve studies of cell phone observation of therapy will be needed to determine if this intervention can improve long-term adherence and health outcomes OBJECTIVE The aim of this r and omized , controlled pilot study was to examine the impact of a pharmacist operated adherence clinic on adherence to highly active antiretroviral therapy ( HAART ) and viral suppression in patients with HIV over 28 weeks . METHODS Consecutive eligible patients initiating HAART at an indigent-care clinic were r and omized to an adherence clinic or to st and ard care ( information provided by physician or nurse practitioner ) for education and monitoring . Group assignment was stratified before r and omization according to regimen complexity and potential tolerability . Adherence ( electronic monitoring and patient self-report ) and viral load ( reverse-transcription polymerase chain reaction ) were assessed at weeks 4 , 16 , and 28 . RESULTS Thirty-three r and omized patients ( adherence clinic , n = 16 ; st and ard care , n = 17 ) comprised the intent-to-treat population . The groups were well-matched for demographics and antiretroviral regimen . The median age was 38.0 years in both groups . Most patients were male ( 85 % ) , had previously used HAART ( 78 % ) , and had an AIDS diagnosis ( 79 % ) . Mean ( SD ) adherence at weeks 4 , 16 , and 28 was 86 % ( 27 % ) , 77 % ( 28 % ) , and 74 % ( 31 % ) in the adherence clinic group versus 73 % ( 32 % ) , 56 % ( 39 % ) , and 51 % ( 41 % ) in the st and ard care group ( week-16 difference , 21 % [ 90 % CI , 1%-42 % ] ; week-28 difference , 23 % [ 90 % CI , 1%-44 % ] ) . Sixty-nine percent of patients in the adherence clinic group took their medication on schedule versus 42 % in the st and ard care group ( P = 0.025 ) ; mean decline in adherence from weeks 4 to 28 was 12 % in the adherence clinic group ( P = 0.15 ) versus 22 % in the st and ard care group ( P = 0.002 ) . HIV-1 RNA levels were < 400 copies/mL at weeks 4 , 16 , and 28 in 63 % , 100 % , and 94 % of the adherence clinic group and 29 % ( P = NS ) , 71 % ( P = 0.04 ) , and 65 % ( P = NS ) of the st and ard care group . CONCLUSIONS In this preliminary trial , an adherence clinic model improved adherence to HAART and virologic response over 28 weeks in the patients studied This intervention sought to improve overall quality of life and health behavior in women living with human immunodeficiency virus ( HIV ) . We contrasted the effect of a group cognitive behavioral stress management expressive supportive therapy ( CBSM+ ) intervention plus a healthier lifestyles ( HL ) component with an individual educational/informational format plus HL on HIV-medication adherence . Women , n = 237 , predominantly African-American and Latina , living with HIV were recruited from Miami , New York and New Jersey and r and omized to group or individual conditions ( ten weekly sessions ) plus group or individual HL , i.e. , four conditions . Women reported relatively high levels of adherence at baseline . Participants in any of the group conditions increased self-reported adherence and emotion-focused coping skills in comparison with individual participation . This study suggests that group interventions may be an important adjunct in increasing medication adherence for HIV positive women OBJECTIVE To determine the efficacy of a peer-led social support intervention involving support groups and telephone contacts compared with st and ard clinical care to enhance antiretroviral medication adherence . DESIGN R and omized controlled trial with follow-up . Participants were 136 HIV-positive indigent mainly African American and Puerto Rican men and women recruited from an outpatient clinic in the Bronx , New York . The 3-month intervention was delivered by other HIV-positive clinic patients trained in addressing barriers to adherence and sensitively providing appraisal , spiritual , emotional , and informational adherence-related social support . MAIN OUTCOME MEASURES Medical chart- abstract ed HIV-1 RNA viral load , antiretroviral adherence according to electronic drug monitoring and participant self-report , and social support and depressive symptomatology . All assessment s conducted at baseline , 3 months , and 6 months . RESULTS Intent-to-treat and as-treated analyses indicated no between-conditions intervention effects on the primary outcome of HIV-1 RNA viral load or any of the secondary outcomes at immediate postintervention or follow-up . Post hoc analyses within the intervention condition indicated greater intervention exposure was associated with higher self-reported adherence , higher social support , and lower depressive symptomatology at follow-up , even after controlling for baseline adherence . CONCLUSION Null findings , consistent with the limited literature on efficacious highly active antiretroviral therapy ( HAART ) adherence interventions , may be due to insufficient exposure to the intervention , its low intensity , or the nature of the sample -a heterogeneous HAART-experienced group of patients with high levels of substance use and multiple other competing stressors . Overall , findings highlight the need for more comprehensive and intensive efforts to battle nonadherence Supervised dosing is a cornerstone of tuberculosis treatment . HIV treatment strategies that use directly administered antiretroviral therapy ( DAART ) are increasingly being assessed . In a prospect i ve single-arm clinical trial , we enrolled methadone-maintained , HIV-infected participants to receive supervised doses of antiretroviral therapy ( ART ) on days when they received methadone . Other ART doses were self-administered . In this analysis we examined factors associated with retention to DAART , adherence to supervised doses , and virologic failure . Factors associated with retention to DAART were assessed with the Kaplan-Meier method and Cox proportional hazards models . Factors associated with nonadherence with supervised dosing and with virologic failure were assessed by logistic regression and techniques for longitudinal data analysis . A total of 16,453 supervised doses were administered to 88 participants over a median follow-up of 9.4 months . The median participant adherence with supervised dosing was 83 % . Active drug use , determined by urine drug screens , was associated twofold increased risks of both intervention dropout and nonadherence with supervised doses . Adherence with supervised doses was strongly associated with virologic failure . Because DAART was administered only on methadone dosing days , fewer than half of the total ART doses were scheduled to be supervised in most participants . The percent of doses that was scheduled to be supervised was not associated with either adherence or with virologic failure . Given that a relatively small proportion of the total ART doses were supervised in many patients , future studies should assess how DAART affects adherence with nonsupervised doses and retention to ART ABSTRACT Adherence to zidovudine ( ZDV ) prophylaxis among 78 pregnant HIV-infected women was measured with 2 physiologic markers . Long-term adherence was measured with blood assays for macrocytosis , a clinical indicator of ZDV use ; 53 women ( 67.9 % ) were adherent . Short-term adherence was measured with urine assays for ZDV ; 48 women ( 61.5 % ) were adherent . Comparison of urine assay and interview data indicated that 29 % had not taken the last dose that they reported . Participation in HIV support groups and disclosure to the participant 's mother were associated with better adherence . These social network factors may enable HIV-infected pregnant women to cope more effectively with the multiple stressors they face and facilitate prenatal care This study describes the effects of a structured , educational/motivational antiretroviral adherence program on virologic and immunologic parameters in HIV-infected patients . Patients were referred because of either self- or provider-identified barriers to adherence . All patients completed 6 to 8 weekly sessions with a nurse or adherence counselor , followed by four quarterly sessions . Sessions included an adherence assessment , individualized patient education , review of adherence strategies , motivational messages , anticipatory planning , and adherence tools . The 58 patients had a mean enrollment CD4 ( + ) count of 223 cells/mm ( 3 ) and mean viral load of 196,454 copies/ml . At the last follow-up , the mean CD4 ( + ) count increased to 308 cells/mm ( 3 ) ( p < .001 ) , and mean viral load decreased to 43,309 ( p < .001 ) . Thirty ( 51.7 % ) patients achieved a viral load < 50 copies/ml at any point during follow-up . Factors associated with final viral load < 50 copies/ml included not being a cigarette smoker , receiving lamivudine in one 's final regimen , and having an HIV risk behavior other than male-male sex Objective : We conducted a r and omized , multi-site , controlled trial of a cognitive-behavioral adherence intervention for patients initiating or changing an antiretroviral ( ART ) regimen . Design : A 3 × 2 factorial design was used with the primary r and omization assigning patients ( 1 : 1 : 1 ) to one of two adherence interventions or usual care . Methods : The five-session adherence interventions consisted of cognitive – behavioral and motivational components , with or without a 2-week pre-treatment placebo practice trial . Intent-to-treat analysis used probability weights and regression tree analysis to account for missing data . Results : A total of 230 patients were r and omized ; 199 started ART , of whom 74 % completed the 48-week study . Electronic monitored adherence outcomes between the two intervention groups did not differ significantly and were thus pooled in analyses . At week 4 , 82 % of intervention patients had taken at least 90 % of their prescribed ART doses , compared with 65 % of controls ( P < 0.01 ) ; this group difference dropped to 12 % at week 12 ( 72 versus 60 % ; P = 0.15 ) and 11 % at week 24 ( 66 versus 55 % ; P = 0.28 ) . Mean adherence in the intervention group was significantly higher than the control group at week 24 ( 89 versus 81 % ; P < 0.05 ) only . There were no group differences with respect to HIV-1 RNA throughout the study . Conclusions : The effects of the cognitive – behavioral intervention on adherence were modest and transient , and no effects were observed on viral load or CD4 cell count . More robust effects may require a more intense intervention that combines ongoing adherence monitoring and individualized intervention ‘ dosage ’ that matches the need and performance of each patient A small pilot trial of a multicomponent ( behavioral strategies , simplified patient information , and social support ) and multidisciplinary ( cognitive-behavioral therapy and nursing ) medication adherence intervention was conducted for HIV-infected adults prescribed antiretrovirals . Patients ( N = 33 ) were r and omly assigned to the intervention condition or st and ard care . Compared to the control group , patients in the intervention condition had significantly higher self-efficacy to communicate with clinic staff ( p = .04 ) and to continue treatment ( p = .04 ) , were significantly more likely to be using behavioral and cognitive strategies ( p = .01 and p = .04 ) , reported significantly higher life satisfaction ( p = .03 ) , reported significantly increased feelings of social support ( p = .04 ) , and showed a trend toward an increase in taking their medications on schedule ( p = .06 ) . The intervention , however , did not appear to affect health-related anxiety or to significantly improve adherence to dose . Implication s for future intervention planning are discussed Background : The relationship between patient adherence and treatment outcomes has been documented across chronic health conditions , but the evidence base for effective adherence interventions in human immunodeficiency virus ( HIV ) and acquired immune deficiency syndrome ( AIDS ) requires more rigorous research and reporting . Objectives : The aims of this study were to determine whether a tailored , nurse-delivered adherence intervention program-Client Adherence Profiling and Intervention Tailoring (CAP-IT)-improved adherence to HIV medications , compared with st and ard care , and to identify the relationship among adherence measures . Methods : A r and omized controlled trial ( RCT ) with repeated measures was used to test the efficacy of CAP-IT over a 6-month period . A convenience sample of 240 participants was recruited from a freest and ing public HIV/AIDS clinic in Houston , TX , that provides medical , psychological , and pharmaceutical services for over 5,000 clients . Study instruments and measures included demographics ; chart audit to capture CD4 count , viral load , and prescribed medications ; health literacy ; and five measures of adherence ( AIDS Clinical Trial Group-Revised Reasons for Missing Medications , Morisky Self-Report of Medication Non-Adherence , Pill Count , Medication Event Monitoring System [ MEMS ] caps , and Pharmacy Refill ) . Results : A logistic regression using generalized estimating equations method showed no significant differences over time on the five medication-adherence measures between the experimental and control groups . Little correlation was documented among the five different adherence measures , and there was minimal correlation with clinical markers . Discussion : It is unclear why the tailored adherence intervention was not efficacious in improving medication adherence . The findings suggest that these measures of medication adherence did not perform as expected and that , perhaps , they are not adequate measures of adherence . Effective and efficient adherence interventions are needed to address the barriers to medication adherence in HIV/AIDS Background : Few rigorously design ed studies have documented the efficacy of interventions to improve medication adherence among patients prescribed highly active antiretroviral . Data are needed to justify the use of limited re sources for these programs . Methods : A 2-arm , r and omized , controlled trial evaluated the efficacy of a community-based , home-visit intervention to improve medication adherence . Participants were 171 HIV-infected adults prescribed a minimum of 3 antiretroviral agents . The majority had a past or current history of substance abuse . Subjects were r and omly assigned to receive home visits for 1 year or usual care . Medication adherence was assessed with Medication Event Monitoring stem caps at 3-month intervals from r and omization through 3 months after the conclusion of the intervention . Results : A larger proportion of subjects in the intervention group demonstrated adherence greater than 90 % compared with the control group at each time point after baseline . The difference over time was statistically significant ( Extended Mantel-Haenszel test : 5.80 , P = 0.02 ) . A statistically significant intervention effect on HIV-RNA level or CD4 cell count was not seen , but there was a statistically significant association between greater than 90 % adherence and an undetectable HIV-RNA over time ( P < 0.03 ) . Conclusion : Home visits from a nurse and a community worker were associated with medication adherence greater than 90 % among a cohort of socially vulnerable people living with HIV/AIDS in northeastern United States Rationale and Purpose : Motivational interviewing ( MI ) is a counseling technique that has been used effectively to change a number of health-related behaviors . We sought to assess the impact on patients ' antiretroviral therapy ( ART ) adherence of a multicomponent , MI-based ART adherence intervention compared with that of an HIV informational control program . Study Design : Two-arm , r and omized , controlled trial . Sample : One hundred forty adult HIV-infected patients attending a large , academic center infectious diseases clinic who were either failing or newly initiating an ART regimen . Study Endpoints : ( 1 ) Mean adherence level ( % of prescribed doses take in the prior month ) at the week 12 visit , ( 2 ) change in mean adherence , ( 3 ) percentage of patients achieving > 95 % adherence in the third 4-week block , and ( 4 ) change in viral load . Main Findings : The MI group 's mean adherence improved by 4.5 % compared with a decrease in the control group 's adherence by 3.83 % ( P = 0.10 ) . In the treatment group , 29 % achieved > 95 % adherence compared with only 17 % in the control group ( P = 0.13 ) . When we controlled for ethnicity , the intervention group had 2.75 times higher odds of achieving more than 95 % adherence than did the controls ( P = 0.045 ; 95 % confidence interval : 1.023 , 7.398 ) . Although a number of mediating variables ( beliefs about ART , coping style , social support , and goals set ) had statistically significant changes in the expected direction in the MI group compared with controls , in the intent-to-treat analysis , the mean adherence at study exit for the intervention group was 76 % ( SD = 27 % ) and 71 % ( SD = 27 % ) for the control group ( P = 0.62 ) . Conclusion : Although not definitive , this study provides some evidence that MI offers an effective approach to improving adherence . Future studies able to build MI into the intervention for longer than 3 months may have a greater impact Several strategies have been introduced to manage nonadherence to highly active antiretroviral therapy ( HAART ) . Treatment with antidepressants may improve self-reported adherence . In this brief report , a small sample of HIV-depressed patients ( n = 9 ) were treated for a 6-month period with antidepressants improving self-reported adherence based on the HAART scale ( poor , good , satisfactory , and optimal ) . Before the antidepressant treatment , adherence was reported as " good " by 3 patients and " satisfactory " by 6 patients . After antidepressant therapy , adherence to antiretroviral regimes was statistically higher in HIV-depressed on treatment than in HIV-depressed patients not treated with antidepressants ( P < 0.0001 ) . We used χ2 test with a significance level at P < 0.05 . Treating depression in HIV-infected patients may serve to improve adherence to HAART R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community Objective : To assess the efficacy of 2 adherence interventions , medication managers ( MM ) and medication alarms ( ALR ) , among antiretroviral (ARV)-naive persons with HIV initiating ARV therapy . Methods : A multicenter , r and omized , adherence intervention clinical trial was conducted among participants coenrolled in an HIV ARV strategy study for ARV-naive individuals . Sites were assigned by cluster r and omization using a 2 × 2 factorial design to administer MM , ALR , MM + ALR , or neither ( control ) . MM participants received individualized , structured , long-term adherence support from trained MMs . ALR participants received individually programmed ALR alarms for use throughout the study . Results : The 928 participants , followed a median of 30 months , included 22 % women and 75 % nonwhites ; the median baseline CD4 count was 155 cells/mm3 . First virologic failure was 13 % lower in all MM versus no-MM groups ( P = 0.13 ) and 28 % lower in MM versus no-MM subgroups r and omized to 2-class ARV arms in the parent ARV study ( P = 0.01 ) . MM ( vs. no-MM ) participants had significantly better CD4 cells count ( P = 0.01 ) and adherence ( P < 0.001 ) outcomes . ALR ( vs. no-ALR ) participants had worse virologic outcomes . Conclusion : This large r and omized clinical trial demonstrated that interpersonal structured adherence support was associated with improved long-term medication adherence and virologic and immunologic HIV outcomes Complex interventions are more than the sum of their parts , and interventions need to be better theorised to reflect this Many people think that st and ardisation and r and omised controlled trials go h and in h and . Having an intervention look the same as possible in different places is thought to be paramount . But this may be why some community interventions have had weak effects . We propose a radical departure from the way large scale interventions are typically conceptualised . This could liberate interventions to be responsive to local context and potentially more effective while still allowing meaningful evaluation in controlled design s. The key lies in looking past the simple elements of a system to embrace complex system functions and processes . The suitability of cluster r and omised trials for evaluating interventions directed at whole communities or organisations remains vexed.1 It need not be.2 Some health promotion advocates ( including the WHO European working group on health promotion evaluation ) believe r and omised controlled trials are inappropriate because of the perceived requirement for interventions in different sites to be st and ardised or look the same.1 3 4 They have ab and oned r and omised trials because they think context level adaptation , which is essential for interventions to work , is precluded by trial design s. An example of context level adaptation might be adjusting educational material s to suit various local learning styles and literacy levels . Lead thinkers in complex interventions , such as the UK 's Medical Research Council , also think that trials of complex interventions must “ consistently provide as close to the same intervention as possible ” by “ st and ardising the content and delivery of the intervention.”5 By contrast , however , they do not see this as a reason to reject r and omised controlled trials . These divergent views have led to problems on two fronts . Firstly , the field of health promotion is being turned away from r and omised Objective : To determine whether proactive telephone support improves adherence to antiretroviral therapy ( ART ) and clinical outcomes when compared to st and ard care . Methods : A multisite , r and omized controlled trial ( RCT ) was conducted with 109 ART-naive subjects coenrolled in AIDS Clinical Trials Group ( ACTG ) 384 . Subjects received st and ard clinic-based patient education ( SC ) or SC plus structured proactive telephone calls . The customized calls were conducted from a central site over 16 weeks by trained registered nurses . Outcome measures ( collected over 64 weeks ) included an ACTG adherence question naire and 384 study endpoints . Results : For the primary endpoint , self-reported adherence , a significantly better overall treatment effect was observed in the telephone group ( P = 0.023 ) . In a post hoc analysis , composite adherence scores , taken as the first 2 factor scores from a principal components analysis , also found significant intervention benefit ( P = 0.023 and 0.019 respectively ) . For the 384 primary study endpoint , time to regimen failure , the Kaplan-Meier survival curve for the telephone group remained above the SC group at weeks 20 to 64 ; a Cox proportional hazard model that controlled for baseline RNA stratification , CD4 , gender , age , race/ethnicity , and r and omized ART treatment arm suggested the telephone group tended to have a lower risk for failure ( hazard ratio = 0.68 ; 95 % confidence interval : 0.38 to 1.23 ) . Conclusions : Findings indicate that customized , proactive telephone calls have good potential to improve long-term adherence behavior and clinical outcomes Abstract A r and omised trial compared two instruments for assessing self-reported adherence to antiretroviral medications : ( 1 ) a day-by-day recall instrument that elicited the number of missed doses in each of the prior three days ( 3-day instrument ; n=64 ) and ( 2 ) a general recall instrument that elicited an estimate of proportion of pills taken during the prior seven days ( 7-day instrument ; n=70 ) . Adherence was measured at study visits over 12 months among participants in a clinical trial assessing treatment strategies for individuals with virologic failure and multidrug-resistant HIV . Participants had a median ( interquartile range ) of 133 ( 41–264 ) CD4 cells/ml3 and a median of 10 major HIV resistance mutations at baseline . Mean adherence levels were 90–98 % throughout the study . There was a greater trend in the likelihood of 100 % adherence when measured by the 3-day versus the 7-day instrument ( odds ratio (OR)=1.45 ; p=0.06 ) . The likelihood of consistent 100 % adherence measured by either instrument decreased over time ( p<0.001 ) . Participants reporting 100 % adherence at more than half of study visits had better virologic and immunologic outcomes at month-12 compared to those reporting 100 % adherence at half or fewer visits ( HIV RNA decline of 0.96 versus 0.51 log , respectively , p=0.02 ; and CD4 cell increase of 51.0 versus 17.8 cells , p=0.04 ) . This study demonstrated the utility of the general 7-day recall adherence self-report instrument as well as the 3-day day-by-day recall adherence self-report instrument for measuring antiretroviral adherence . Self-reported adherence was significantly associated with virologic and immunologic outcomes in this population with advanced drug-resistant HIV disease |
2,147 | 27,562,037 | We discuss implication s that the identification of these practice elements found in the early childhood literature has for efforts to implement models and practice | Educators are increasingly being encouraged to implement evidence -based interventions and practice s to address the social , emotional , and behavioral needs of young children who exhibit problem behavior in early childhood setting s. Given the nature of social-emotional learning during the early childhood years and the lack of a common set of core evidence -based practice s within the early childhood literature , selection of instructional practice s that foster positive social , emotional , and behavioral outcomes for children in early childhood setting s can be difficult .
The purpose of this paper is to report findings from a study design ed to identify common practice elements found in comprehensive intervention models ( i.e. , manualized interventions that include a number of components ) or discrete practice s ( i.e. , a specific behavior or action ) design ed to target social , emotional , and behavioral learning of young children who exhibit problem behavior . | This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Research Findings : This study examined processes of change associated with the positive preschool and kindergarten outcomes of children who received the Head Start REDI ( REsearch -based , Developmentally Informed ) intervention compared to usual practice Head Start . Using data from a large-scale r and omized controlled trial ( N = 356 children , 42 % African American or Latino , all from low-income families ) , this study tests the logic model that improving preschool social-emotional skills ( e.g. , emotion underst and ing , social problem solving , and positive social behavior ) as well as language /emergent literacy skills will promote cross-domain academic and behavioral adjustment after children transition into kindergarten . Validating this logic model , the present study finds that intervention effects on 3 important kindergarten outcomes ( e.g. , reading achievement , learning engagement , and positive social behavior ) were mediated by preschool gains in the proximal social-emotional and language /emergent literacy skills targeted by the REDI intervention . It is important to note that preschool gains in social-emotional skills made unique contributions to kindergarten outcomes in reading achievement and learning engagement , even after we accounted for concurrent preschool gains in vocabulary and emergent literacy skills . Practice or Policy : These findings highlight the importance of fostering at-risk children 's social-emotional skills during preschool as a means of promoting school readiness The Incredible Years ( IY ) Series includes separate group interventions to improve parenting interactions , teacher classroom management , and child social-emotional regulation . Although originally developed to treat early onset conduct problems , IY targets many of the proposed mechanisms and risk factors for internalizing distress in early childhood . Prior studies have demonstrated the effects of the IY parent intervention on co-occurring depressive symptoms . We attempted to extend these findings by examining the unique and combined effects of IY interventions on children 's co-occurring internalizing symptoms . One-hundred and fifty-nine families with children ages 4- to 8-years-old were r and omly assigned to parent training ( PT ) ; parent plus teacher training ( PT + TT ) ; child training ( CT ) ; child plus teacher training ( CT + TT ) ; parent , child , plus teacher training ( PT + CT + TT ) ; or a waiting list control group . Children who received any of the intervention components were more likely to have lower mother-rated internalizing symptoms at posttreatment compared to children in a wait-list control group . Implication s for future research and for design ing interventions and prevention strategies for children with internalizing symptoms are discussed . ( PsycINFO Data base This study evaluated the post-treatment outcome effects of a classroom-based social skills program for pre-kindergarten children , using a teacher-consultation model . The pre-K RECAP ( Reaching Educators , Children , and Parents ) program is a semi-structured , cognitive-behavioral skills training program that provides teachers with in-classroom consultation on program implementation and classroom-wide behavior management . Data on children 's social skills and behavior problems were collected from parents and teachers at pre- and post-treatment , for 149 children aged 4–5 years ( of whom 56 % were girls ) . Significant treatment effects were found for teacher but not parent reports , with treatment group children improving significantly more than comparison group children in their teacher-rated social skills and internalizing and externalizing problems . These results provide some preliminary support for the efficacy of the program on children 's social skills and behavior problems , and for a teacher-consultation model for training teachers to implement school-based mental health programs Background There is an urgent need for effective , affordable interventions to prevent child mental health problems in low- and middle-income countries . Aims To determine the effects of a universal pre-school-based intervention on child conduct problems and social skills at school and at home . Method In a cluster r and omised design , 24 community pre-schools in inner-city areas of Kingston , Jamaica , were r and omly assigned to receive the Incredible Years Teacher Training intervention ( n = 12 ) or to a control group ( n = 12 ) . Three children from each class with the highest levels of teacher-reported conduct problems were selected for evaluation , giving 225 children aged 3–6 years . The primary outcome was observed child behaviour at school . Secondary outcomes were child behaviour by parent and teacher report , child attendance and parents ’ attitude to school . The study is registered as IS RCT N35476268 . Results Children in intervention schools showed significantly reduced conduct problems ( effect size ( ES ) = 0.42 ) and increased friendship skills ( ES = 0.74 ) through observation , significant reductions to teacher-reported ( ES = 0.47 ) and parent-reported ( ES = 0.22 ) behaviour difficulties and increases in teacher-reported social skills ( ES = 0.59 ) and child attendance ( ES = 0.30 ) . Benefits to parents ’ attitude to school were not significant . Conclusions A low-cost , school-based intervention in a middle-income country substantially reduces child conduct problems and increases child social skills at home and at school This study applied the distillation and matching model to 322 r and omized clinical trials for child mental health treatments . The model involved initial data reduction of 615 treatment protocol descriptions by means of a set of codes describing discrete clinical strategies , referred to as practice elements . Practice elements were then summarized in profiles , which were empirically matched to client factors ( i.e. , observed problem , age , gender , and ethnicity ) . Results of a profile similarity analysis demonstrated a branching of the literature into multiple problem areas , within which some age and ethnicity special cases emerged as higher order splits . This is the 1st study to aggregate evidence -based treatment protocol s empirically according to their constituent treatment procedures , and the results point both to the overall organization of therapy procedures according to matching factors and to gaps in the current child and adolescent treatment literature Separate studies of rural and urban Head Start systems tested the hypothesis that an emotion-based prevention program ( EBP ) would accelerate the development of emotion and social competence and decrease agonistic behavior and potential precursors of psychopathology . In both studies , Head Start centers were r and omly assigned to treatment and control/comparison group conditions . In Study 1 ( rural community ) , results of hierarchical linear modeling analyses showed that compared to the control condition ( Head Start as usual ) , EBP produced greater increases in emotion knowledge and emotion regulation and greater decreases in children 's negative emotion expressions , aggression , anxious/depressed behavior , and negative peer and adult interactions . In Study 2 ( inner city ) , compared to the established prevention program I Can Problem Solve , EBP led to greater increases in emotion knowledge , emotion regulation , positive emotion expression , and social competence . In Study 2 , emotion knowledge mediated the effects of EBP on emotion regulation , and emotion competence ( an aggregate of emotion knowledge and emotion regulation ) mediated the effects of EBP on social competence This r and omized controlled trial ( RCT ) evaluated the efficacy of the Incredible Years ( IY ) Teacher Classroom Management ( TCM ; Webster-Stratton & Reid , 2002 ) program to assess whether training teachers in IY-TCM principles improve teacher behavior , whether any observed improvements impact pupil behavior classroom-wide , and whether these effects can be demonstrated with children at risk of developing conduct problems . Six intervention and six control classrooms comprising 12 teachers and 107 children ( aged 3 to 7years ) were recruited . Children were screened for high or low behavior problems using the cut-off points of the teacher-rated Strengths and Difficulties Question naire ( Goodman , 1997 ) . The primary outcome measure was independent classroom observations using the Teacher-Pupil Observation Tool ( Martin et al. , 2010 ) . Multilevel modeling analyses were conducted to examine the effect of the intervention on teacher , classroom , and child behavior . Results showed a significant reduction in classroom off-task behavior ( d=0.53 ) , teacher negatives to target children ( d=0.36 ) , target child negatives towards the teacher ( d=0.42 ) , and target child off-task behavior ( d=0.48 ) . These preliminary results demonstrate the potential impact of IY-TCM on both teacher and child behavior This paper reports the results from a r and omized clinical trial evaluating an adaptation of the Promoting Alternative Thinking Strategies curriculum ( PATHS ) for preschool-age children in Head Start . PATHS is a universal , teacher-taught social-emotional curriculum that is design ed to improve children ’s social competence and reduce problem behavior . Twenty classrooms in two Pennsylvania communities participated in the study . Teachers in the 10 intervention classrooms implemented weekly lessons and extension activities across a 9-month period . Child assessment s and teacher and parent reports of child behavior assessment s were collected at the beginning and end of the school year . Analysis of covariance was used to control for baseline differences between the groups and pretest scores on each of the outcome measures . The results suggest that after exposure to PATHS , intervention children had higher emotion knowledge skills and were rated by parents and teachers as more socially competent compared to peers . Further , teachers rated intervention children as less socially withdrawn at the end of the school year compared to controls . Editors ’ Strategic Implication s : n Findings from this and other r and omized clinical trials confirm that the Preschool PATHS program is clearly a promising practice for improving children ’s social and emotional competence . Head Start and school programs will find these multi-informant data to be of interest as they consider a curriculum to help prepare children for school entry Behavior problems among preschool children are common . They are important targets for intervention because early externalizing problems and self-regulation issues tend to persist without appropriate attention , and can affect later mental health and school achievement outcomes . However , few preschool curricula addressing social and emotional development exist , and evidence for effects are mixed . In this study , the Second Step Pre/Kindergarten Social and Emotional Learning curriculum was adapted and tested in a small cluster r and omized pilot study of community preschool classrooms to determine if it could improve outcomes in : ( 1 ) individual children ’s teacher-rated behavior problems and prosocial skills ; ( 2 ) classroom climate ( classroom interactions and two measures of disruptive behavior ) ; and ( 3 ) teacher interaction skills . Year 1 outcomes were modest and were accounted for by baseline differences . In Year 2 , classroom climate , measured by independent observers , differed significantly in intervention classrooms , largely because of declines in control classrooms , and there was some evidence for better teacher interaction skills in intervention classrooms . The pattern of effects suggests important impacts on classroom quality worth investigating in a larger study . Both fidelity and implementation rates , as well as positive teacher responses to the curriculum , indicate potential for widespread adoption The present study evaluated the efficacy of a multicomponent , classroom-based intervention in reducing preschoolers ' behavior problems . The Chicago School Readiness Project model was implemented in 35 Head Start classrooms using a clustered-r and omized controlled trial design . Results indicate significant treatment effects ( ds = 0.53 - 0.89 ) for teacher-reported and independent observations of children 's internalizing and externalizing behavior problems . Moreover , there was some evidence for the moderating role of child gender , race/ethnic group membership , and exposure to poverty-related risk , with stronger effects of intervention for some groups of children than for others . Findings contribute to a growing area of research on poverty and preventive intervention in early childhood Children with behavioral , emotional or language problems struggle to do well at school often with limited success . ABLE ( Attention , Behavior , Language , and Emotions ) , a new screening tool , was used to estimate the prevalence and the severity of concerns parents and teachers have about children 's school adjustment and evaluate their need for services . Data obtained from the parents and teachers of children r and omly selected from public Pre-K classrooms in 6 states ( N = 415 ) and from a mental health screening of rural and urban children ( N = 5,577 ) support the validity and reliability of ABLE . Parents identified severe problems in 18.4 % of children and Pre-K teachers identified 10.5 % . By kindergarten , the proportion of children identified by their teachers with serious problems more than doubled to 23 % . Inattention/overactivity and behavior problems were identified most often . These children were 3.4 times more likely to be certified later for special education services by kindergarten than children not identified with problems by ABLE . However , fewer than 14 % of children in public Pre-K identified with serious problems in Pre-K had received mental health services by the end of Kindergarten Families of 159 , 4- to 8-year-old children with oppositional defiant disorder ( ODD ) were r and omly assigned to parent training ( PT ) ; parent plus teacher training ( PT + TT ) ; child training ( CT ) ; child plus teacher training ( CT + TT ) ; parent , child , plus teacher training ( PT + CT + TT ) ; or a waiting list control . Reports and independent observations were collected at home and school . Following the 6-month intervention , all treatments result ed in significantly fewer conduct problems with mothers , teachers , and peers compared to controls . Children 's negative behavior with fathers was lower in the 3 PT conditions than in control . Children showed more prosocial skills with peers in the CT conditions than in control . All PT conditions result ed in less negative and more positive parenting for mothers and less negative parenting for fathers than in control . Mothers and teachers were also less negative than controls when children received CT . Adding TT to PT or CT improved treatment outcome in terms of teacher behavior management in the classroom and in reports of behavior problems BACKGROUND School readiness , conceptualized as three components including emotional self-regulation , social competence , and family/school involvement , as well as absence of conduct problems play a key role in young children 's future interpersonal adjustment and academic success . Unfortunately , exposure to multiple poverty-related risks increases the odds that children will demonstrate increased emotional dysregulation , fewer social skills , less teacher/parent involvement and more conduct problems . Consequently intervention offered to socio-economically disadvantaged population s that includes a social and emotional school curriculum and trains teachers in effective classroom management skills and in promotion of parent-school involvement would seem to be a strategic strategy for improving young children 's school readiness , leading to later academic success and prevention of the development of conduct disorders . METHODS This r and omized trial evaluated the Incredible Years ( IY ) Teacher Classroom Management and Child Social and Emotion curriculum ( Dinosaur School ) as a universal prevention program for children enrolled in Head Start , kindergarten , or first grade classrooms in schools selected because of high rates of poverty . Trained teachers offered the Dinosaur School curriculum to all their students in bi-weekly lessons throughout the year . They sent home weekly dinosaur homework to encourage parents ' involvement . Part of the curriculum involved promotion of lesson objectives through the teachers ' continual use of positive classroom management skills focused on building social competence and emotional self-regulation skills as well as decreasing conduct problems . Matched pairs of schools were r and omly assigned to intervention or control conditions . RESULTS Results from multi-level models on a total of 153 teachers and 1,768 students are presented . Children and teachers were observed in the classrooms by blinded observers at the beginning and the end of the school year . Results indicated that intervention teachers used more positive classroom management strategies and their students showed more social competence and emotional self-regulation and fewer conduct problems than control teachers and students . Intervention teachers reported more involvement with parents than control teachers . Satisfaction with the program was very high regardless of grade levels . CONCLUSIONS These findings provide support for the efficacy of this universal preventive curriculum for enhancing school protective factors and reducing child and classroom risk factors faced by socio-economically disadvantaged children Forty-four Head Start classrooms were r and omly assigned to enriched intervention ( Head Start REDI- Research -based , Developmentally Informed ) or " usual practice " conditions . The intervention involved brief lessons , " h and s-on " extension activities , and specific teaching strategies linked empirically with the promotion of : ( a ) social-emotional competencies and ( b ) language development and emergent literacy skills . Take-home material s were provided to parents to enhance skill development at home . Multi method assessment s of three hundred and fifty-six 4-year-old children tracked their progress over the course of the 1-year program . Results revealed significant differences favoring children in the enriched intervention classrooms on measures of vocabulary , emergent literacy , emotional underst and ing , social problem solving , social behavior , and learning engagement . Implication s are discussed for developmental models of school readiness and for early educational programs and policies This article tests the hypothesis that children 's learning environment will improve through a social and emotional learning ( SEL ) intervention that provides preschool teachers with new skills to manage children 's disruptive behavior by reporting results from the Foundations of Learning ( FOL ) Demonstration , a place-r and omized , experimental evaluation conducted by MDRC . Research Findings : Findings demonstrate that the FOL intervention improved teachers ' ability to address children 's behavior problems and to provide a positive emotional climate in their classrooms . Importantly , the FOL intervention also improved the number of minutes of instructional time , although the quality of teachers ' instruction was not improved . Finally , FOL benefited children 's observed behavior in classrooms , with lower levels of conflictual interactions and , at the trend level , higher levels of engagement in classrooms activities , relative to similar students r and omly assigned to control classrooms . Practice or Policy : This study is one of an emerging body of research on the efficacy of SEL programs for preschool children living in poverty . Underst and ing the value-added of these programs ( e.g. , in increased instructional time and increased classroom engagement ) as well as their limitations ( e.g. , in teachers ' instructional quality and children 's academic skills ) will help us design the next set of more effective interventions for low-income children We evaluated the effects of the preschool life skills program ( PLS ; Hanley , Heal , Tiger , & Ingvarsson , 2007 ) on the acquisition and maintenance of functional communication and self-control skills , as well as its effect on problem behavior , of small groups of preschoolers at risk for school failure . Six children were taught to request teacher attention , teacher assistance , and preferred material s , and to tolerate delays to and denial of those events during child-led , small-group activities . Teaching strategies included instruction , modeling , role play , and differential reinforcement . Six additional children r and omly assigned to similarly sized control groups participated in small-group activities but did not experience the PLS program . Within-subject and between-groups design s showed that the PLS teaching procedures were functionally related to the improvements and maintenance of the skills and prevention of problem behavior . Stakeholder responses on a social acceptability question naire indicated that they were satisfied with the form of the targeted social skills , the improvements in the children 's performance , and the teaching strategies |
2,148 | 27,848,150 | Additionally , studies in Asian subjects , studies in Japanese subjects , and studies conducted in Japan showed relations when three classifications regarding ethnicity and study regions were applied . | Background and objectiveS everal systematic review s and meta-analyses have been conducted including an analysis to investigate the difference between ethnic groups in the glucose-lowering efficacy of dipeptidyl peptidase-4 ( DPP-4 ) inhibitors .
This study assessed the factors related to the glucose-lowering efficacy and explored potential differences among ethnicities ; in particular , Japanese subjects were dealt separately from other Asian subjects . | Aims : Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy . Methods and patients : A total of 768 patients ( 18–77 years ; HbA1c screening ≥ 7.5 to ≤ 10.0 % ) were r and omised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks . Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg . Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology . Results : At week 24 , 92 % of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day . Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide , respectively , in HbA1c ( −0.54 % , −0.64 % vs. + 0.08 % ; both p < 0.0001 ) and fasting plasma glucose ( −7 , −10 vs. + 1 mg/dl ; p = 0.0218 and p = 0.002 ) . The proportion of patients achieving an HbA1c < 7 % was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( 22.4 % and 22.8 % vs. 9.1 % ; both p < 0.0001 ) . Postpr and ial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( −4296 and −5000 vs. + 1196 mg·min/dl ; both p < 0.0001 ) . Adverse event occurrence was similar across all groups . Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 ( 13.3 % ) and 5 mg ( 14.6 % ) vs. uptitrated glyburide ( 10.1 % ) . Conclusion : Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated AIMS To investigate the efficacy and safety of linagliptin , a dipeptidyl peptidase-4 inhibitor , in type 2 diabetes mellitus ( T2DM ) patients for whom metformin was inappropriate . METHODS This 1-year double-blind study ( Clinical Trials.gov , NCT00740051 ) enrolled T2DM patients with inadequate glycaemic control , treatment-naïve [ glycated haemoglobin ( HbA1c ) 7.0 - 10.0 % ] or previously treated with one oral antidiabetes drug ( HbA1c 6.5 - 9.0 % before washout ) , ineligible for metformin because of contraindications ( e.g. renal impairment ) or previous intolerable side effects . Patients were r and omized to monotherapy with linagliptin 5 mg once daily ( n = 151 ) or placebo ( n = 76 ) for 18 weeks , after which placebo patients switched to glimepiride 1 - 4 mg once daily and treatments continued for another 34 weeks . The primary endpoint was change from baseline in HbA1c after 18 weeks ( full- analysis set , last observation carried forward ) . RESULTS At week 18 , adjusted mean difference in change from baseline HbA1c ( 8.1 % ) was -0.60 % ( 95 % confidence interval -0.88 , -0.32 ; p < 0.0001 ) ( -0.39 % with linagliptin , + 0.21 % with placebo ) . At week 52 , mean HbA1c was decreased from baseline in both groups [ linagliptin : -0.44 % ; placebo/glimepiride : -0.72 % ( observed cases ) ] . Adverse events occurred in 40.4 and 48.7 % of linagliptin and placebo patients , respectively , during the initial 18 weeks . During the 34-week extension , patients receiving linagliptin experienced less hypoglycaemia ( 2.2 % vs. 7.8 % ) and no weight gain ( mean change from baseline of -0.2 and + 1.3 kg , respectively ) compared with glimepiride patients . CONCLUSIONS In T2DM patients for whom metformin was inappropriate , linagliptin improved glycaemic control and was well tolerated , with less hypoglycaemia and relative weight loss compared with glimepiride Aims To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type 2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone . Methods This was a multi-centre , phase 3 , r and omized , double-blind , placebo-controlled study comparing linagliptin 5 mg once daily ( n = 183 ) and placebo ( n = 89 ) as add-on to metformin and pioglitazone . The primary endpoint was the change from baseline in glycated haemoglobin ( HbA1c ) after 24 weeks . Results The placebo-corrected adjusted mean ( se ) change in HbA1c from baseline to 24 weeks was –6 ( 1 ) mmol/mol [ –0.57 (0.13)% ] ( P < 0.0001 ) . In patients with baseline HbA1c ≥ 53 mmol/mol ( 7.0 % ) , 32.4 % of patients in the linagliptin group and 13.8 % in the placebo group achieved HbA1c < 53 mmol/mol ( 7.0 % ) ( odds ratio 2.94 ; P = 0.0033 ) . The placebo-corrected adjusted mean ( se ) change from baseline in fasting plasma glucose at week 24 was –0.57 ( 0.26 ) mmol/l [ –10.4 ( 4.7 ) mg/dl ] ( P = 0.0280 ) . The incidence of serious adverse events was 2.2 % with linagliptin and 3.4 % with placebo . Investigator-defined hypoglycaemia occurred in 5.5 % of the linagliptin group and 5.6 % of the placebo group . No meaningful changes in mean body weight were noted for either group . Conclusions Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinical ly meaningful improvements in glycaemic control , without an additional risk of hypoglycaemia or weight gain ( Clinical Trials Registry No : NCT 00996658 ) AIM To assess the safety and efficacy of the potent and selective dipeptidyl peptidase-4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment-naive or who had received one oral antidiabetes drug ( OAD ) . METHODS This multicentre , r and omized , parallel group , phase III study compared linagliptin treatment ( 5 mg once daily , n = 336 ) with placebo ( n = 167 ) for 24 weeks in type 2 diabetes patients . Before r and omization , patients pretreated with one OAD underwent a washout period of 6 weeks , which included a placebo run-in period during the last 2 weeks . Patients previously untreated with an OAD underwent a 2-week placebo run-in period . The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment . RESULTS Linagliptin treatment result ed in a placebo-corrected change in HbA1c from baseline of -0.69 % ( p < 0.0001 ) at 24 weeks . In patients with baseline HbA1c ≥ 9.0 % , the adjusted reduction in HbA1c was 1.01 % ( p < 0.0001 ) . Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5 % at 24 weeks than those in the placebo arm ( 47.1 and 19.0 % , respectively ; odds ratio , OR = 4.2 , p < 0.0001 ) . Fasting plasma glucose improved by -1.3 mmol/l ( p < 0.0001 ) with linagliptin vs. placebo , and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postpr and ial glucose of -3.2 mmol/l ( p < 0.0001 ) . Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025 ) , Homeostasis Model Assessment -%B ( p = 0.049 ) and disposition index ( p = 0.0005 ) . There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention . Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin . CONCLUSIONS Monotherapy with linagliptin produced a significant , clinical ly meaningful and sustained improvement in glycaemic control , accompanied by enhanced parameters of β-cell function . The safety profile of linagliptin was comparable with that of placebo Abstract Aims / Introduction The efficacy and safety of sitagliptin , a highly selective dipeptidyl peptidase‐4 inhibitor , when added to metformin monotherapy was examined in Japanese patients with type 2 diabetes . Material s and Methods In this 52‐week , add‐on to metformin study , 149 patients were r and omly assigned to receive sitagliptin 50 mg or placebo once daily in a double‐blind fashion for 12 weeks . Thereafter , all patients who completed the double‐blind period of the study received open‐label sitagliptin 50 mg once daily for 40 weeks , with the investigator option of increasing sitagliptin to 100 mg once daily for patients who met predefined glycemic thresholds . Results After 12 weeks of treatment , the mean change from baseline in glycated hemoglobin ( HbA1c ) significantly decreased with sitagliptin relative to placebo ( between‐group difference [ 95 % confidence interval ] = −0.7 % [ −0.9 to −0.5 ] P < 0.001 ) . At week 12 , the mean changes in 2‐h post‐meal glucose ( −2.6 mmol/L [ −3.5 to −1.7 ] ) and fasting plasma glucose ( −1.0 mmol/L [ −1.3 to −0.6 ] ) also decreased significantly with sitagliptin relative to placebo ( P < 0.001 for both ) . Significant improvements from baseline in glycemic control were also observed in the open‐label period through to week 52 . There were no differences between treatment groups in the incidence of adverse events ( AEs ) , including hypoglycemia and predefined gastrointestinal AEs ( nausea , vomiting and diarrhea ) during the double‐blind period , with similar findings in the open‐label period . Conclusions Over a period of 52 weeks , the addition of sitagliptin once‐daily to ongoing metformin therapy was efficacious and generally well tolerated in Japanese patients with type 2 diabetes . This trial was registered with Clinical Trials.gov ( no. NCT00363948 ) Background To compare the safety and efficacy of saxagliptin 2.5 mg twice daily ( BID ) versus placebo add-on therapy to metformin immediate release ( IR ) in patients with type 2 diabetes and inadequate glycemic control with metformin alone . Methods This multicenter , 12-week , double-blind , parallel-group trial enrolled adult out patients with type 2 diabetes ( glycated hemoglobin [ HbA1c ] 7.0%–10.0 % ) on stable metformin IR monotherapy ( ≥1500 mg , BID for ≥8 weeks ) . Patients were r and omized to double-blind saxagliptin 2.5 mg BID or placebo added on to metformin IR following a 2-week , single-blind , placebo add-on therapy lead-in period . The primary end point was the change from baseline to week 12 in HbA1c . Key secondary end points included change from baseline to week 12 in fasting plasma glucose ( FPG ) and the proportion of patients achieving HbA1c < 7.0 % or HbA1c ≤ 6.5 % at week 12 . Efficacy was analyzed in all patients who received r and omized study drug with ≥1 postbaseline assessment . Safety was assessed in all treated patients . Results In total , 74 patients were r and omized to double-blind saxagliptin add-on therapy and 86 to placebo add-on therapy . At week 12 , least-squares mean changes ( 95 % CI ) from baseline HbA1c ( adjusted for baseline HbA1c ) were significantly greater ( P = 0.006 ) in the saxagliptin + metformin group -0.56 % ( -0.74 % to -0.38 % ) versus the placebo + metformin group -0.22 % ( -0.39 % to -0.06 % ) . Adjusted mean changes from baseline in FPG were numerically greater with saxagliptin versus placebo ; the difference ( 95 % CI ) -9.5 mg/dL ( -21.7 to 2.7 ) was not statistically significant ( P = 0.12 ) . A numerically greater proportion of patients in the saxagliptin group than the placebo group achieved HbA1c < 7.0 % ( 37.5 % vs 24.2 % ) or HbA1c ≤6.5 % ( 24.6 % vs 10.7 % ) . There were no unexpected safety findings . Hypoglycemia occurred in 4 patients ( 5.4 % ) in the saxagliptin group and 1 patient ( 1.2 % ) in the placebo group ; confirmed hypoglycemia ( symptoms plus fingerstick glucose ≤50 mg/dL ) occurred in 1 patient in the placebo group . Conclusions Addition of saxagliptin 2.5 mg BID to metformin therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy reduced HbA1c compared with placebo added to metformin , with an adverse events profile similar to placebo and no unexpected safety findings .Trial registration Clinical Trials.gov OBJECTIVE —To evaluate the dipeptidyl peptidase-4 ( DPP-4 ) inhibitor alogliptin in drug-naïve patients with inadequately controlled type 2 diabetes . RESEARCH DESIGN AND METHODS —This double-blind , placebo-controlled , multicenter study included 329 patients with poorly controlled diabetes r and omized to once-daily treatment with 12.5 mg alogliptin ( n = 133 ) , 25 mg alogliptin ( n = 131 ) , or placebo ( n = 65 ) for 26 weeks . Primary efficacy end point was mean change from baseline in A1C at the final visit . RESULTS —At week 26 , mean change in A1C was significantly greater ( P < 0.001 ) for 12.5 mg ( −0.56 % ) and 25 mg ( −0.59 % ) alogliptin than placebo ( −0.02 % ) . Reductions in fasting plasma glucose were also greater ( P < 0.001 ) in alogliptin-treated patients than in those receiving placebo . Overall , incidences of adverse events ( 67.4–70.3 % ) and hypoglycemia ( 1.5–3.0 % ) were similar across treatment groups . CONCLUSIONS —Alogliptin monotherapy was well tolerated and significantly improved glycemic control in patients with type 2 diabetes , without raising the incidence of hypoglycemia Abstract Aims / Introduction Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control . The present multicenter , r and omized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy ( 0.2–0.3 mg three times daily ) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control ( glycated hemoglobin ≥6.9 % and < 10.5 % ) . Material s and Methods The present study had an initial 12‐week , double‐blind treatment period in which patients were r and omized ( 1:1 ) to sitagliptin 50 mg/day ( n = 70 ) or placebo ( n = 63 ) , followed by a 40‐week , open‐label treatment period during which all patients received sitagliptin 50 mg/day , that could have been increased to 100 mg/day for patients meeting predefined glycemic criteria . Results After 12 weeks , treatment with sitagliptin result ed in placebo‐subtracted mean changes from baseline in glycated hemoglobin ( the primary end‐point ) , fasting plasma glucose and 2‐h postmeal glucose of –0.9 % , –22.5 mg/dL and –51.3 mg/dL , respectively ( all , P < 0.001 ) . During the double‐blind period , adverse experiences were reported with similar frequency in both treatment groups , and the occurrences of hypoglycemia and gastrointestinal adverse experiences were low . In the open‐label period , sustained improvements in glycemic parameters were observed with sitagliptin treatment , and sitagliptin was generally well tolerated . Conclusions Sitagliptin added on to ongoing voglibose monotherapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control . This trial was registered with Clinical Trails.gov ( no. NCT00837577 ) AIMS The efficacy and safety of the dipeptidyl peptidase-4 inhibitor , linagliptin , added to ongoing metformin therapy , were assessed in patients with Type 2 diabetes who had inadequate glycaemic control ( HbA(1c ) ≥ 7.5 to ≤ 10 % ; ≥ 58.5 to ≤ 85.8 mmol/mol ) with metformin alone . METHODS Patients ( n=333 ) were r and omized to receive double-blind linagliptin ( 1 , 5 or 10 mg once daily ) or placebo or open-label glimepiride ( 1 - 3 mg once daily ) . The primary outcome measure was the change from baseline in HbA(1c ) at week 12 in patients receiving combination therapy compared with metformin alone . RESULTS Twelve weeks of treatment result ed in a mean ( sem ) placebo-corrected lowering in HbA(1c ) levels of 0.40 % ( ± 0.14 ) ; 4.4 mmol/mol ( ± 1.5 ) for 1 mg linagliptin , 0.73 % ( ± 0.14 ) ; 8.0 mmol/mol ( ± 1.5 ) for 5 mg , and 0.67 % ( ± 0.14 ) ; 7.3 mmol/mol ( ± 1.5 ) for 10 mg . Differences between linagliptin and placebo were statistically significant for all doses ( 1 mg , P = 0.01 ; 5 mg and 10 mg , P < 0.0001 ) . The change in mean ( sem ) placebo-corrected HbA(1c ) from baseline was -0.90 % ( ± 0.13 ) ; -9.8 mmol/mol ( ± 1.4 ) for glimepiride . Adjusted and placebo-corrected mean changes in fasting plasma glucose were -1.1 mmol/l for linagliptin 1 mg ( P = 0.002 ) , -1.9 mmol/l for 5 mg and -1.6 mmol/l for 10 mg ( both P < 0.0001 ) . One hundred and six ( 43.1 % ) patients reported adverse events ; the incidence was similar across all five groups . There were no hypoglycaemic events for linagliptin or placebo , whereas three patients ( 5 % ) receiving glimepiride experienced hypoglycaemia . CONCLUSIONS The addition of linagliptin to ongoing metformin treatment in patients with Type 2 diabetes was well tolerated and result ed in significant and clinical ly relevant improvements in glycaemic control , with 5 mg linagliptin being the most effective dose OBJECTIVE To assess the efficacy and tolerability of vildagliptin ( 10 , 25 or 50 mg bid ) in Japanese patients with type 2 diabetes mellitus ( T2DM ) . METHODS This 12-week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study was performed in 291 patients . The primary assessment was change from baseline to endpoint in HbA1c . RESULTS Baseline HbA1c averaged 7.4 % , and the between-treatment difference ( vildagliptin-placebo ) in the HbA1c adjusted mean change was -0.8 % , -1.0 % and -1.2 % with vildagliptin 10 , 25 and 50 mg bid , respectively ( p<0.001 ) . Relative to baseline , body weight did not change significantly in vildagliptin groups . There was no increase in incidence of adverse events in the vildagliptin groups ( 62.0 % , 62.5 % and 61.8 % , 10 , 25 and 50 mg bid , respectively ) compared to placebo ( 73.6 % ) . No deaths or drug-related serious adverse events were reported . Seven hypoglycemic events were observed ( four events ( n=3 ) , two events ( n=2 ) , and one event ( n=1 ) in the vildagliptin 10 and 50 mg bid , and placebo , respectively ) and none of them were severe or dose related . CONCLUSION Vildagliptin 50 mg bid was considered to be the most effective and well-tolerated dose , and therefore can be considered the recommended clinical dose for Japanese patients with T2DM BACKGROUND Few studies have assessed the use of new oral anti-diabetic agents in Asian population s. This study assesses the efficacy and safety of saxagliptin versus placebo in Asian patients with type 2 diabetes mellitus ( T2DM ) . MATERIAL S AND METHODS Five hundred sixty-eight drug-naïve adult patients with T2DM and glycated haemoglobin levels ( HbA(1c ) ) of 7.0 - 10.0 % ( 53 - 86 mmol/mol ) were r and omized 1 : 1 to receive saxagliptin 5 mg daily or placebo . Efficacy endpoints included changes from baseline to week 24 in HbA(1c ) , fasting plasma glucose ( FPG ) , post-pr and ial glucose area under the curve from 0 to 180 min ( PPG AUC(0 - 180 ) ) , and the proportion of patients achieving HbA(1c ) < 7.0 % ( 53 mmol/mol ) . Adverse events ( AEs ) and serious AEs ( SAEs ) were evaluated . RESULTS Saxagliptin provided statistically significant adjusted mean decreases from baseline to week 24 compared with placebo , respectively , in HbA(1c ) ( -0.84 % [ -9 mmol/mol ] versus -0.34 % [ -4 mmol/mol ] ; p < 0.0001 ) , FPG ( -0.90 versus -0.17 mmol/L ; p < 0.0001 ) , and PPG AUC(0 - 180 ) ( -417 versus -235 mmol · min/L ; p = 0.0010 ) . A significantly greater proportion of patients achieved a therapeutic glycaemic response ( HbA(1c ) < 7.0 % [ 53 mmol/mol ] ) with saxagliptin ( 45.8 % ) versus placebo ( 28.8 % ; p < 0.0001 ) . The proportions of patients who experienced ≥1 AE ( excluding hypoglycaemia ) was 43.3 % for saxagliptin and 35.6 % for placebo . Few patients in either treatment group experienced an SAE ( 2.8 % , saxagliptin ; 1.4 % , placebo ) . A low proportion of patients reported hypoglycaemic events ( 1.8 % , saxagliptin ; 0.7 % , placebo ) . CONCLUSIONS Saxagliptin improved glycaemic control and was well tolerated in drug-naïve Asian patients with T2DM Aims /hypothesisThe aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin . Methods This r and omised , double-blind , four-arm , parallel-group , Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012 . Participants ( N = 1,284 ) with type 2 diabetes aged ≥18 and ≤80 years who had inadequate glycaemic control ( HbA1c ≥7.0 % [ 53 mmol/mol ] and ≤10.5 % [ 91 mmol/mol ] ) on metformin therapy received canagliflozin 100 mg or 300 mg , sitagliptin 100 mg , or placebo ( n = 368 , 367 , 366 , 183 , respectively ) for a 26 week , placebo- and active-controlled period followed by a 26 week , active-controlled period ( placebo group switched to sitagliptin [ placebo/sitagliptin ] ) and were included in the modified intent-to-treat analysis set . R and omisation was performed using a computer-generated schedule ; participants , study centres and the sponsor were blinded to group assignment . The primary endpoint was change from baseline in HbA1c at week 26 ; secondary endpoints included changes in HbA1c ( week 52 ) and fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( BP ; weeks 26 and 52 ) . Adverse events ( AEs ) were recorded throughout the study . Results At week 26 , canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo ( −0.79 % , –0.94 % , –0.17 % , respectively ; p < 0.001 ) . At week 52 , canagliflozin 100 mg and 300 mg demonstrated non-inferiority , and canagliflozin 300 mg demonstrated statistical superiority , to sitagliptin in lowering HbA1c ( −0.73 % , –0.88%,–0.73 % , respectively ) ; differences ( 95 % CI ) vs sitagliptin were 0 % ( −0.12 , 0.12 ) and −0.15 % ( −0.27 , –0.03 ) , respectively . Canagliflozin 100 mg and 300 mg reduced body weight vs placebo ( week 26 : –3.7 % , –4.2 % , –1.2 % , respectively ; p < 0.001 ) and sitagliptin ( week 52 : –3.8 % , –4.2 % , –1.3 % , respectively ; p < 0.001 ) . Both canagliflozin doses reduced FPG and systolic BP vs placebo ( week 26 ) and sitagliptin ( week 52 ) ( p < 0.001 ) . Overall AE and AE-related discontinuation rates were generally similar across groups , but higher with canagliflozin 100 mg . Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin ; few led to discontinuations . Hypoglycaemia incidence was higher with canagliflozin . Conclusions /interpretationCanagliflozin improved glycaemia and reduced body weight vs placebo ( week 26 ) and sitagliptin ( week 52 ) and was generally well tolerated in patients with type 2 diabetes on metformin . Clinical trial registry Clinical Trials.gov NCT01106677 Funding This study was supported by Janssen Research & Development , LLC Sitagliptin is an oral , potent , highly selective , once-daily DPP-4 inhibitor indicated for the treatment of type 2 diabetes mellitus ( T2DM ) . To assess the dose-ranging efficacy and safety/tolerability profile of once-daily sitagliptin 25 , 50 , 100 , and 200 mg in Japanese patients with T2DM . In this r and omized , double-blind , placebo-controlled study , 363 Japanese patients with inadequate glycemic control ( HbA(1c)=6.5 - 10 % ; FPG < or = 270 mg/dL ) were r and omized ( 1:1:1:1:1 ) to placebo , sitagliptin 25 , 50 , 100 , or 200 mg q.d . for 12 weeks . The primary endpoint was change from baseline in HbA(1c ) at Week 12 . At Week 12 , treatment with sitagliptin at all doses tested provided significant ( p<0.001 ) reductions in HbA(1c ) ( -0.69 to -1.04 % ) from baseline ( 7.49 to 7.65 % ) relative to placebo . Sitagliptin significantly ( p<0.001 ) reduced fasting plasma glucose ( FPG ; -15.9 to -23.2 mg/dL ) and 2-hour postpr and ial glucose ( 2-hr PPG ; -40.3 to -65.0 mg/dL ) relative to placebo , in a dose-dependent manner . At doses > or = 50 mg , differences in HbA(1c ) , FPG , and 2-hr PPG between the sitagliptin groups were not statistically significant . Sitagliptin was generally well tolerated with a low and similar incidence of hypoglycemia and minimal weight gain relative to placebo . Treatment with sitagliptin for 12 weeks provided significant and clinical ly meaningful reductions in HbA(1c ) , FPG , and 2-hr PPG across the dose range studied and was generally well tolerated in Japanese patients with T2DM UNLABELLED This 24-week , double-blind , r and omized , multicenter , placebo-controlled , parallel-group study performed in 354 drug-naïve patients with type 2 diabetes ( T2DM ) assessed efficacy and tolerability of vildagliptin ( 50 mg qd , 50 mg bid , or 100 mg qd ) . The primary assessment was change from baseline to endpoint in hemoglobin A1c ( A1C ) , comparing vildagliptin to placebo by ANCOVA . Baseline A1C averaged 8.4 % and the between-treatment difference ( vildagliptin-placebo ) in adjusted mean change ( AMDelta ) in A1C was -0.5+/-0.2 % ( P=0.011 ) , -0.7+/-0.2 % ( P<0.001 ) , and -0.9+/-0.2 % ( P<0.001 ) in patients receiving vildagliptin 50 mg qd , 50 mg bid , or 100 mg qd , respectively . Baseline FPG averaged 10.5 mmol/L ; the between-treatment difference in AMDelta FPG was -0.6+/-0.4 mmol/L in patients receiving vildagliptin 50 mg qd and -1.3+/-0.4 mmol/L ( P=0.001 ) in both groups receiving 100 mg daily . Relative to baseline , body weight did not change significantly in any of the three vildagliptin groups and decreased by 1.4+/-0.4 kg in the placebo group . Adverse events ( AEs ) occurred with similar frequency in each group : 55.8 % , 59.3 % , 59.3 % , and 57.6 % of patients receiving vildagliptin 50 mg qd , 50 mg bid , 100 mg qd , or placebo , respectively , experienced an AE . No confirmed hypoglycemia was reported . CONCLUSION Vildagliptin is effective and well-tolerated in drug-naïve patients with T2DM and 100 mg vildagliptin provides similar clinical benefit whether given as single or in divided doses AIM To assess the efficacy and safety of a 24-week treatment with sitagliptin , a highly selective once-daily oral dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , in patients with type 2 diabetes who had inadequate glycaemic control [ glycosylated haemoglobin ( HbA(1c ) ) > or=7.5 % and < or=10.5 % ] while on glimepiride alone or in combination with metformin . METHODS After a screening , diet/exercise run-in and drug wash-off period , a glimepiride + /- metformin dose titration/stabilization period and a 2-week , single-blind placebo run-in , 441 patients ( of ages 18 - 75 years ) were r and omized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks . Of these patients , 212 were on glimepiride ( > or=4 mg/day ) monotherapy and 229 were on glimepiride ( > or=4 mg/day ) plus metformin ( > or=1,500 mg/day ) combination therapy . Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy ( pioglitazone ) until study end . The primary efficacy analysis evaluated the change in HbA(1c ) from baseline to Week 24 . Secondary efficacy endpoints included fasting plasma glucose ( FPG ) , 2-h post-meal glucose and lipid measurements . RESULTS Mean baseline HbA(1c ) was 8.34 % in the sitagliptin and placebo groups . After 24 weeks , sitagliptin reduced HbA(1c ) by 0.74 % ( p < 0.001 ) relative to placebo . In the subset of patients on glimepiride plus metformin , sitagliptin reduced HbA(1c ) by 0.89 % relative to placebo , compared with a reduction of 0.57 % in the subset of patients on glimepiride alone . The addition of sitagliptin reduced FPG by 20.1 mg/dl ( p < 0.001 ) and increased homeostasis model assessment -beta , a marker of beta-cell function , by 12 % ( p < 0.05 ) relative to placebo . In patients who underwent a meal tolerance test ( n = 134 ) , sitagliptin decreased 2-h post-pr and ial glucose ( PPG ) by 36.1 mg/dl ( p < 0.001 ) relative to placebo . The addition of sitagliptin was generally well tolerated , although there was a higher incidence of overall ( 60 vs. 47 % ) and drug-related adverse experiences ( AEs ) ( 15 vs. 7 % ) in the sitagliptin group than in the placebo group . This was largely because of a higher incidence of hypoglycaemia AEs ( 12 vs. 2 % , respectively ) in the sitagliptin group compared with the placebo group . Body weight modestly increased with sitagliptin relative to placebo ( + 0.8 vs. -0.4 kg ; p < 0.001 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy . The addition of sitagliptin was generally well tolerated , with a modest increase in hypoglycaemia and body weight , consistent with glimepiride therapy and the observed degree of glycaemic improvement Abstract Aims / Introduction To evaluate the efficacy and safety of alogliptin added to treatment with glimepiride . Material s and Methods This multicenter , r and omized , double‐blind , parallel‐group , 24‐week ( 12‐week observation and 12‐week treatment ) study compared alogliptin 12.5 or 25 mg in combination with glimepiride ( 1–4 mg/day ) vs placebo added to glimepiride monotherapy in Japanese patients with type 2 diabetes who had poor glycemic control despite treatment with diet and exercise plus a sulfonylurea . The primary end‐point was a change in glycated hemoglobin ( HbA 1c ) from baseline . A 40‐week open‐label extension study evaluated the long‐term safety and efficacy of the combination . Results Alogliptin 12.5 or 25 mg in combination with glimepiride significantly decreased HbA 1c compared with glimepiride monotherapy after 12 weeks ' treatment ( −0.59 , −0.65 and 0.35 % , respectively ; P < 0.0001 for both combination groups vs glimepiride monotherapy ) . Alogliptin 12.5 and 25 mg combination therapy was also associated with significantly higher responder rates ( HbA 1c < 6.9 % : 9.6 % and 7.7 % , HbA 1c < 7.4 % : 29.8 % and 34.6 % ) compared with glimepiride monotherapy ( HbA 1c < 6.9 % : 0 % , HbA 1c < 7.4 % : 3.9 % ) . The incidence of adverse events was comparable between glimepiride monotherapy and alogliptin combination treatment , with most reported adverse events being mild in severity . In the extension study , the incidence of adverse events was comparable between the combination groups , with the majority of adverse events being mild . Conclusions Once‐daily alogliptin was effective and generally well tolerated when given as add‐on therapy to glimepiride in Japanese patients with type 2 diabetes who had inadequate glycemic control on sulfonylurea plus lifestyle measures . Clinical benefits were maintained for 52 weeks . This trial was registered with Clinical Trials.gov ( double‐blind study no. NCT01318083 ; long‐term study no. NCT01318135 ) OBJECTIVE The efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy were assessed in patients with type 2 diabetes and inadequate glycemic control ( glycosylated hemoglobin [ HbA(1c ) ] > or = 7 % and < or = 10 % ) while receiving a stable dose of pioglitazone . METHODS This was a 24-week , multicenter , r and omized , double-blind , placebo-controlled , parallel group study in patients aged > or = 18 years ( Clinical Trials . gov NCT00086502 ) . At screening , all patients began a diet/exercise program that continued throughout the study period . Patients taking antihyperglycemic therapy other than pioglitazone underwent a washout of this therapy and entered an 8- to 14-week open-label pioglitazone dose-titration/stabilization period . Patients with an HbA(1c ) > or = 7 % and < or = 10 % at the end of this period entered a 2-week , single-blind , placebo run-in period ( total duration of run-in period , up to 21 weeks ) . Patients who had been receiving pioglitazone monotherapy ( 30 or 45 mg/d ) and had an HbA(1c ) > or = 7 % and < or = 10 % entered the 2-week , single-blind , placebo run-in period directly . Thus , at the time of r and omization , all patients were receiving ongoing pioglitazone ( 30 or 45 mg/d ) . Patients were r and omized in a 1:1 ratio to receive sitagliptin 100 mg once daily or placebo for 24 weeks . The primary efficacy end point was the change from baseline in HbA(1c ) at week 24 . Secondary efficacy end points included the change from baseline in fasting plasma glucose ( FPG ) , insulin , and proinsulin ; the Homeostasis Model Assessment beta-cell function and insulin-resistance indexes ; the proinsulin/ insulin ratio ; the Quantitative Insulin Sensitivity Check Index ; the percent changes from baseline in selected lipid parameters ; the proportion of patients meeting the American Diabetes Association HbA(1c ) , goal of < 7.0 % ; the proportion of patients requiring metformin rescue therapy ; and the time to the initiation of rescue therapy . RESULTS One hundred seventy-five patients were r and omized to receive sitagliptin , and 178 were r and omized to receive placebo . The mean ( SD ) baseline HbAlc value was 8.1 % ( 0.8 ) in the sitagliptin group and 8.0 % ( 0.8 ) in the placebo group . After 24 weeks , sitagliptin added to pioglitazone therapy was associated with significant reductions compared with placebo in HbA(1c ) ( between-treatment difference in least squares [ LS ] mean change from baseline . -0.70 % ; 95 % CI , -0.85 to -0.54 ; P < 0.001 ) and FPG ( -17.7 mg/dL ; 95 % CI , -24.3 to -11.0 ; P < 0.001 ) . Mean HbA(1c ) values at end point were 7.2 % ( 0.9 ) and 7.8 % ( 1.1 ) in the respective treatment groups , and the proportions of patients reaching a target HbA(1c ) of < 7.0 % were 45.4 % and 23.0 % ( P < 0.001 ) . Significant reductions in fasting serum proinsulin levels and the proinsulin/insulin ratio were seen with sitagliptin treatment compared with placebo ( both , P < 0.01 ) . Sitagliptin was generally well tolerated , with no increased risk of hypoglycemia compared with placebo ( 2 vs 0 patients , respectively ) AIM To assess the efficacy and safety of alogliptin added to pioglitazone versus pioglitazone monotherapy , in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on pioglitazone plus diet/exercise . METHODS Patients were stabilized on pioglitazone 15 or 30 mg/day plus diet/exercise during a 16-week screening period . Patients with HbA1c of 6.9 - 10.4 % were r and omized to 12 weeks ' double-blind treatment with alogliptin 12.5 or 25 mg once daily or placebo , added to their stable pioglitazone regimen . The primary endpoint was the change in HbA1c from baseline to week 12 . Patients had an option to continue in a 40-week , open-label extension study , with those originally r and omized to alogliptin remaining on the same dosage regimen while patients treated with placebo were r and omly allocated to alogliptin 12.5 or 25 mg ( added to their stable pioglitazone ) . RESULTS The change from baseline in HbA1c after 12 weeks was significantly greater with alogliptin 12.5 mg added to pioglitazone and alogliptin 25 mg added to pioglitazone than with placebo added to pioglitazone ( -0.91 and -0.97 % vs. -0.19 % ; p < 0.0001 ) . Responder rates ( HbA1c < 6.9 % and HbA1c < 6.2 % ) and changes in fasting and postpr and ial blood glucose levels showed a similar positive trend in terms of glycaemic control . The benefits seen with alogliptin were sustained during the 40-week extension period . Alogliptin added to pioglitazone was generally well tolerated ; hypoglycaemia was infrequent and increases in body weight were minor . CONCLUSIONS Once-daily alogliptin was effective and generally well tolerated when given as add-on therapy to pioglitazone in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on pioglitazone plus lifestyle measures . Clinical benefits were maintained for 52 weeks AIMS To evaluate the efficacy and safety of linagliptin 5 and 10 mg vs. placebo and voglibose in Japanese patients with type 2 diabetes mellitus ( T2DM ) . METHODS This study enrolled patients with inadequately controlled T2DM who were previously treated with one or two oral antidiabetics or were drug naÏve . After a 2 to 4-week washout and placebo run-in , 561 patients were r and omized ( 2 : 2 : 2 : 1 ) to double-blind treatment with linagliptin 5 or 10 mg qd , voglibose 0.2 mg tid or placebo . The primary endpoint was the change from baseline in haemoglobin A1c ( HbA1c ) with linagliptin vs. placebo after 12 weeks and vs. voglibose after 26 weeks . RESULTS Baseline characteristics were well balanced across treatment groups ( overall mean HbA1c was 8.01 % ) . The adjusted mean ( 95 % confidence interval ) treatment differences at week 12 were -0.87 % ( -1.04 , -0.70 ; p < 0.0001 ) and -0.88 % ( -1.05 , -0.71 ; p < 0.0001 ) for linagliptin 5 and 10 mg vs. placebo and at week 26 were -0.32 % ( -0.49 , -0.15 ; p = 0.0003 ) and -0.39 % ( -0.56 , -0.21 ; p < 0.0001 ) for linagliptin 5 and 10 mg vs. voglibose . At week 12 , mean HbA1c was 7.58 , 7.48 and 8.34 % in patients receiving linagliptin 5 mg , linagliptin 10 mg and placebo , respectively . At week 26 , mean HbA1c was 7.63 % with linagliptin 5 mg , 7.50 % with linagliptin 10 mg and 7.91 % with voglibose . Drug-related adverse event rates were comparable across treatment groups over 12 weeks ( 9.4 % linagliptin 5 mg , 8.8 % linagliptin 10 mg and 10.0 % placebo ) and 26 weeks ( 11.3 % linagliptin 5 mg , 10.6 % linagliptin 10 mg and 18.5 % voglibose ) . There were no documented cases of hypoglycaemia . CONCLUSIONS Linagliptin showed superior glucose-lowering efficacy and comparable safety and tolerability to both placebo and voglibose in Japanese patients with T2DM Abstract Introduction The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here . Material s and Methods This was a multicenter , r and omized , double‐blind , placebo‐controlled , parallel group , 24‐week clinical trial carried out in China . Patients ( n = 744 ) with type 2 diabetes and inadequate glycemic control ( glycated hemoglobin ≥7.5 and ≤11.0 % ) who were either drug‐naïve or washed out of previous therapy were r and omized in equal ratios to sitagliptin 100 mg once daily ( q.d . ; S100 ) , metformin 500 mg twice daily ( b.i.d . ; M1000 ) , metformin 850 mg b.i.d . ( M1700 ) , sitagliptin 50 mg b.i.d . plus metformin 500 mg b.i.d . ( S100/M1000 ) , sitagliptin 50 mg b.i.d . plus metformin 850 mg b.i.d . ( S100/M1700 ) , or placebo . Results The mean baseline glycated hemoglobin in r and omized patients was 8.7 % . Least squares mean changes from baseline in glycated hemoglobin were −0.59 % ( placebo ) , −0.99 % ( S100 ) , −1.29 % ( M1000 ) , −1.56 % ( M1700 ) , −1.67 % ( S100/M1000 ) and −1.83 % ( S100/M1700 ) ( P < 0.05 for each active group vs placebo , for S100/M1700 and S100/M1000 vs S100 , and for S100/M1000 vs M1000 ) . All treatments were generally well‐tolerated . The overall incidence of hypoglycemia ( symptomatic or asymptomatic ) was higher in the two co‐administration groups ( S100/M1700 and S100/M1000 ) compared with the placebo . The incidence of symptomatic hypoglycemia was low , and similar , across all treatment groups . The incidences of gastrointestinal adverse events were generally higher in high‐dose metformin groups than in the placebo group . Conclusions In Chinese patients with type 2 diabetes , initial combination therapy with sitagliptin and metformin was generally well‐tolerated , and provided improvement in glycemic control Abstract Aims / Introduction : Patients with type 2 diabetes mellitus often require treatment with more than one oral antihyperglycemic agent to achieve their glycemic goal . The present study was carried out to assess the efficacy and safety of sitagliptin as add‐on therapy in Japanese patients with type 2 diabetes mellitus inadequately controlled ( HbA1c ≥ 6.9 % and < 10.4 % ) on pioglitazone monotherapy ( 15–45 mg/day ) . Material s and Methods : In the initial 12‐week , double‐blind treatment period , patients were r and omized ( 1:1 ) to sitagliptin 50 mg/day ( n = 66 ) or placebo ( n = 68 ) , followed by a 40‐week open‐label treatment period in which all patients received sitagliptin 50 mg/day that could have been increased to 100 mg/day for patients meeting predefined glycemic parameters . Results : After 12 weeks , mean changes from baseline in HbA1c ( the primary end‐point ) , fasting plasma glucose and 2‐h post‐meal glucose were −0.8 % , −0.9 mmol/L and −2.7 mmol/L , respectively , in the sitagliptin group compared with placebo ( all P < 0.001 ) . The incidence of adverse experiences during the double‐blind treatment period was similar in both treatment groups , and the incidences of hypoglycemia and gastrointestinal adverse experiences were low . In the open‐label period , improvements in glycemic parameters with sitagliptin treatment were maintained and sitagliptin was generally well tolerated . Conclusions : Sitagliptin as add‐on therapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus inadequately controlled on pioglitazone monotherapy . This trial was registered with Clinical Trials.gov ( no. NCT00372060 ) . ( J Diabetes Invest , doi : 10.1111/j.2040‐1124.2011.00120.x , 2011 OBJECTIVE This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control with metformin alone . RESEARCH DESIGN AND METHODS This was a r and omized , double-blind , placebo-controlled study of saxagliptin ( 2.5 , 5 , or 10 mg once daily ) or placebo plus a stable dose of metformin ( 1,500–2,500 mg ) in 743 patients ( A1C ≥7.0 and ≤10.0 % ) . Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary ( A1C ) and secondary ( fasting plasma glucose [ FPG ] and postpr and ial glucose [ PPG ] area under the curve [ AUC ] ) end points . RESULTS Saxagliptin ( 2.5 , 5 , and 10 mg ) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C ( −0.59 , −0.69 , and −0.58 vs. + 0.13 % ; all P < 0.0001 ) , FPG ( −14.31 , −22.03 , and −20.50 vs. + 1.24 mg/dl ; all P < 0.0001 ) , and PPG AUC ( −8,891 , −9,586 , and −8,137 vs. −3,291 mg · min/dl ; all P < 0.0001 ) . More than twice as many patients achieved A1C < 7.0 % with 2.5 , 5 , and 10 mg saxagliptin versus placebo ( 37 , 44 , and 44 vs. 17 % ; all P < 0.0001 ) . β-Cell function and postpr and ial C-peptide , insulin , and glucagon AUCs improved in all saxagliptin treatment groups at week 24 . Incidence of hypoglycemic adverse events and weight reductions were similar to those with placebo . CONCLUSIONS Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with metformin alone Aims / Introduction Asian patients represent a large portion of the global population with type 2 diabetes mellitus , but are underrepresented in trials of glucose-lowering therapies . The present r and omized , phase III , placebo-controlled , double-blind , 24-week study evaluated the dipeptidyl peptidase-4 inhibitor , linagliptin , as monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus . Material s and Methods Patients who were treatment naïve or had been treated with one oral antidiabetes drug were r and omized to either linagliptin 5 mg daily or a placebo after washout . The primary end-point was a change from baseline in glycated hemoglobin after 24 weeks . Results A total of 300 Asian ( 87 % Chinese ) patients with type 2 diabetes mellitus were r and omized to linagliptin or placebo at a 2:1 ratio . After 24 weeks of treatment , adjusted mean ( st and ard error ) glycated hemoglobin decreased by a placebo-corrected −0.50 ± 0.11 ( P < 0.0001 ) . In patients with baseline glycated hemoglobin ≥8.5 % , the placebo-corrected decrease in glycated hemoglobin was −0.91 ± 0.20 % ( P < 0.0001 ) . Adverse events occurred in 28.0 and 28.3 % of linagliptin and placebo patients , respectively , but few were drug-related ( 3.0 and 2.0 % , respectively ) . Hypoglycemia was reported by one linagliptin patient and no placebo patients . Treatment with linagliptin was weight neutral . Conclusions In Asian patients with inadequately controlled type 2 diabetes mellitus , linagliptin 5 mg as monotherapy was efficacious and well tolerated over 24 weeks Introduction The objective of this study was to evaluate the efficacy and safety of vildagliptin , a potent dipeptidyl peptidase-4 inhibitor , as an add-on to metformin in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods This multicenter , 12-week , r and omized , double-blind , placebo-controlled , parallel-arm study compared vildagliptin 50 mg bid with placebo in T2DM patients who were inadequately controlled [ glycosylated hemoglobin ( HbA1c ) 7.0–10.0 % ] on a stable daily dose of metformin monotherapy ( 250 mg bid or 500 mg bid ) . Results A total of 139 patients were r and omized to receive either vildagliptin ( n = 69 ) or placebo ( n = 70 ) . Patient demographics were comparable between the groups at baseline . After 12 weeks of treatment , adjusted mean change in HbA1c was −1.1 % in the vildagliptin group ( baseline 8.0 % ) and −0.1 % in the placebo group ( baseline 8.0 % ) , with a between-treatment difference of −1.0 % ( P < 0.001 ) . Vildagliptin showed a similar reduction in HbA1c of −1.1 % for both the sub population s of patients receiving metformin 250 mg bid or 500 mg bid ( P < 0.001 vs. baseline ) . Significantly more patients in the vildagliptin group achieved an HbA1c target of ≤6.5 % ( 30.9 % ) and < 7.0 % ( 64.1 % ) compared with the placebo group ( P < 0.001 ) . The between-treatment difference in adjusted mean change in fasting plasma glucose was −1.6 mmol/L ( P < 0.001 ) in favor of vildagliptin . Patients in the vildagliptin and placebo groups reported comparable incidences of adverse events ( 44.1 % vs. 41.4 % ) . No deaths or hypoglycemic events were reported in the study . Conclusions Vildagliptin 50 mg bid added to metformin improved glycemic control without any tolerability issues and hypoglycemia in Japanese patients with T2DM inadequately controlled on metformin monotherapy CONTEXT Due to the natural progression of type 2 diabetes ( T2D ) , most patients require combination therapy to maintain glycemic control . OBJECTIVE Our objective was to evaluate efficacy and safety of saxagliptin plus thiazolidinedione ( TZD ) in patients with T2D and inadequate glycemic control on TZD monotherapy . DESIGN The study was a multicenter , r and omized , double-blind , placebo (PBO)-controlled phase 3 trial conducted from March 13 , 2006 , to October 15 , 2007 . SETTING Patients were recruited from 172 outpatient centers . PATIENTS Patients with inadequately controlled T2D [ glycosylated hemoglobin ( HbA(1c ) ) 7.0 - 10.5 % ] , 18 - 77 yr , receiving stable TZD monotherapy ( pioglitazone 30 or 45 mg or rosiglitazone 4 or 8 mg ) for at least 12 wk before screening were eligible . INTERVENTIONS A total of 565 patients were r and omized and treated with saxagliptin ( 2.5 or 5 mg ) or PBO , once daily , plus stable TZD dose for 24 wk . MAIN OUTCOME MEASURES Primary outcome was change in HbA(1c ) from baseline to wk 24 . Secondary outcomes were change from baseline to wk 24 in fasting plasma glucose , proportion of patients achieving HbA(1c ) less than 7.0 % , and postpr and ial glucose area under the curve . RESULTS At 24 wk , saxagliptin ( 2.5 and 5 mg ) plus TZD demonstrated statistically significant adjusted mean decreases vs. PBO in HbA(1c ) [ -0.66 % ( P = 0.0007 ) and -0.94 % ( P < 0.0001 ) vs. -0.30 % ] and fasting plasma glucose [ -0.8 mmol/liter ( P = 0.0053 ) and -1 mmol/liter ( P = 0.0005 ) vs. -0.2 mmol/liter ] . Proportion of patients achieving HbA(1c ) less than 7.0 % was greater for saxagliptin ( 2.5 and 5 mg ) plus TZD vs. PBO [ 42.2 % ( P = 0.001 ) and 41.8 % ( P = 0.0013 ) vs. 25.6 % ] . Postpr and ial glucose area under the curve was significantly reduced [ -436 mmol x min/liter ( saxagliptin 2.5 mg plus TZD ) and -514 mmol x min/liter ( saxagliptin 5 mg plus TZD ) vs. -149 mmol x min/liter ( PBO ) ] . Saxagliptin was generally well tolerated ; adverse event occurrence and reported hypoglycemic events were similar across all groups . CONCLUSIONS Saxagliptin added to TZD provided statistically significant improvements in key parameters of glycemic control vs. TZD monotherapy and was generally well tolerated Aims /hypothesisThe aim of this study was to assess the efficacy and safety of sitagliptin ( MK-0431 ) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control ( HbA1c ≥7 % and ≤10 % ) on exercise and diet . Methods A total of 521 patients aged 27–76 years with a mean baseline HbA1c of 8.1 % were r and omised in a 1:2:2 ratio to treatment with placebo , sitagliptin 100 mg once daily , or sitagliptin 200 mg once daily , for 18 weeks . The efficacy analysis was based on an all- patients -treated population using an analysis of covariance , excluding data obtained after glycaemic rescue . Results After 18 weeks , HbA1c was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo ( placebo-subtracted HbA1c reduction : −0.60 % and −0.48 % , respectively ) . Sitagliptin also significantly decreased fasting plasma glucose relative to placebo . Patients with higher baseline HbA1c ( ≥9 % ) experienced greater placebo-subtracted HbA1c reductions with sitagliptin ( −1.20 % for 100 mg and −1.04 % for 200 mg ) than those with HbA1c < 8 % ( −0.44 % and −0.33 % , respectively ) or ≥8 % to 8.9 % ( −0.61 % and −0.39 % , respectively ) . Homeostasis model assessment beta cell function index and fasting proinsulin : insulin ratio , markers of insulin secretion and beta cell function , were significantly improved with sitagliptin . The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo . Sitagliptin had a neutral effect on body weight . Conclusions /interpretationSitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet AIMS To evaluate the efficacy and safety of initial combination therapy with linagliptin plus metformin versus linagliptin or metformin monotherapy in patients with type 2 diabetes . METHODS In this 24-week , double-blind , placebo-controlled , Phase III trial , 791 patients were r and omized to one of six treatment arms . Two free combination therapy arms received linagliptin 2.5 mg twice daily ( bid ) + either low ( 500 mg ) or high ( 1000 mg ) dose metformin bid . Four monotherapy arms received linagliptin 5 mg once daily , metformin 500 mg or 1000 mg bid or placebo . Patients with haemoglobin A1c ( HbA1c ) ≥11.0 % were not eligible for r and omization and received open-label linagliptin + high-dose metformin . RESULTS The placebo-corrected mean ( 95 % confidence interval ) change in HbA1c from baseline ( 8.7 % ) to week 24 was -1.7 % ( -2.0 , -1.4 ) for linagliptin + high-dose metformin , -1.3 % ( -1.6 , -1.1 ) for linagliptin + low-dose metformin , -1.2 % ( -1.5 , -0.9 ) for high-dose metformin , -0.8 % ( -1.0 , -0.5 ) for low-dose metformin and -0.6 ( -0.9 , -0.3 ) for linagliptin ( all p < 0.0001 ) . In the open-label arm , the mean change in HbA1c from baseline ( 11.8 % ) was -3.7 % . Hypoglycaemia occurred at a similar low rate with linagliptin + metformin ( 1.7 % ) as with metformin alone ( 2.4 % ) . Adverse event rates were comparable across treatment arms . No clinical ly significant changes in body weight were noted . CONCLUSIONS Initial combination therapy with linagliptin plus metformin was superior to metformin monotherapy in improving glycaemic control , with a similar safety and tolerability profile , no weight gain and a low risk of hypoglycaemia AIM To assess efficacy and safety of saxagliptin added to metformin versus placebo plus metformin in Asian patients with type 2 diabetes mellitus ( T2DM ) and inadequate glycemic control on metformin alone . METHODS Adults ( HbA(1c ) 7.0 - 10.0 % , on stable metformin ≥ 1500 mg/day ) were r and omized 1:1 to saxagliptin 5 mg daily plus metformin ( n = 283 ) or placebo plus metformin ( n = 287 ) . The primary end point was HbA(1c ) change from baseline to Week 24 . RESULTS Saxagliptin plus metformin provided significant adjusted mean decreases versus placebo plus metformin ( p ≤ 0.0052 ) in HbA(1c ) ( -0.78 % versus -0.37 % ) , fasting plasma glucose ( -1.14 mmol/L versus -0.58 mmol/L ) , and postpr and ial glucose area under the curve from 0 to 180 min ( -315 mmol min/L versus -160 mmol min/L ) . Significantly more saxagliptin-treated patients achieved a therapeutic glycemic response ( HbA(1c)<7.0 % ) ( 46.5 % versus 30.5 % ; p = 0.0001 ) . The proportion of patients experiencing adverse events ( excluding hypoglycemia ) was similar for saxagliptin plus metformin ( 42.8 % ) versus placebo plus metformin ( 40.8 % ) . Hypoglycemic events were reported in 1.4 % of patients in each group . CONCLUSION Saxagliptin added to metformin significantly improved glycemic control and was well tolerated in Asian patients with T2DM who had inadequate glycemic control with metformin and diet and lifestyle modification Efficacy and tolerability of sitagliptin , a dipeptidyl peptidase-4 inhibitor , were assessed in Japanese patients with type 2 diabetes . In a multicenter , double-blind , r and omized , placebo-controlled trial in Japan , 151 patients with inadequate glycemic control [ HbA(1c ) > or = 6.5 % to < 10 % , fasting plasma glucose ( FPG ) > or = 126 to < or = 240 mg/dL ] were r and omized to once-daily sitagliptin 100 mg or placebo for 12 weeks . After 12 weeks , the least squares ( LS ) mean change from baseline HbA(1c ) was -0.65 % ( 95 % CI : -0.80 , -0.50 ) with sitagliptin versus 0.41 % ( 0.26 , 0.56 ) with placebo [ between-group difference=-1.05 % ( -1.27 , -0.84 ) ; p<0.001 ] . LS mean change from baseline FPG was -22.5mg/dL ( 95 % CI : -28.0 , -17.0 ) with sitagliptin versus 9.4 mg/dL ( 3.9 , 14.9 ) with placebo [ between-group difference=-31.9 mg/dL ( 95 % CI : -39.7,-24.1 ) ; p<0.001 ] . More patients achieved HbA(1c ) < 7 % or < 6.5 % with sitagliptin than with placebo ( p<0.001 ) . Following a meal tolerance test , 2-h postpr and ial glucose was significantly reduced with sitagliptin relative to placebo . Clinical and laboratory adverse experiences were similar between treatments , with no reported hypoglycemia adverse events with sitagliptin . Body weight was unchanged relative to baseline in the sitagliptin group ( -0.1 kg ) , but significantly ( p<0.01 ) different relative to the placebo group ( -0.7 kg ) . In this study , once-daily sitagliptin 100 mg for 12 weeks improved fasting and postpr and ial glycemic control and was generally well tolerated in Japanese patients with type 2 diabetes Abstract Objective : To compare the efficacy and safety of alogliptin and placebo as add-on therapy in Japanese patients with type 2 diabetes who experienced inadequate glycemic control on voglibose plus diet/exercise therapy . Research design and methods : During an 8 week screening phase , patients aged ≥20 years were stabilized on voglibose 0.2 mg three times daily plus diet/exercise therapy . Those with HbA1c between ≥6.9 % and < 10.4 % were r and omly assigned to 12 weeks ’ double-blind treatment with once daily alogliptin 12.5 or 25 mg , or placebo . The primary endpoint was the change in HbA1c at 12 weeks from baseline . Patients then entered an open-label , 40 week extension trial ( patients in the placebo group were r and omly allocated to alogliptin 12.5 or 25 mg ) . Clinical trials registration : www . clinical trials.gov ; pivotal trial NCT01263483 ; Long term trial NCT01263509 . Results : Least square mean change in HbA1c after 12 weeks ’ therapy from baseline ( primary endpoint ) was significantly greater in the alogliptin 12.5 mg ( −0.96 % ; P < 0.0001 ) and 25 mg ( −0.93 % ; P < 0.0001 ) groups compared with placebo ( + 0.06 % ) . This was associated with statistically significant improvements in other measures of glycemic control , in particular sustained reductions in fasting plasma glucose and postpr and ial plasma glucose . These benefits were maintained for the duration of the 1 year study and , importantly , they were achieved without detrimental effects on tolerability/safety . In particular , there was no increase in the rate of hypoglycemia and almost no changes in mean body weight . Conclusions : Addition of once daily alogliptin to voglibose monotherapy in Japanese patients with uncontrolled type 2 diabetes produced clinical ly significant improvements in glycemic control , and was well tolerated Abstract Objective : To compare the efficacy and safety of different dosages of alogliptin with that of placebo and voglibose in drug-naïve Japanese patients with type 2 diabetes inadequately controlled by diet and exercise . Research design and methods : In the double-blind , placebo-controlled phase of this two-part study , 480 patients aged ≥20 years with type 2 diabetes mellitus ( HbA1c ≥6.9 % to < 10.4 % ) were r and omized to monotherapy with alogliptin 6.25 , 12.5 , 25 or 50 mg once daily , placebo , or voglibose 0.2 mg three times daily for a period of 12 weeks . In a subsequent open-label , long-term extension phase , patients continued on the same treatment for an additional 40 weeks ( patients in the placebo group were reassigned equally to one of the four alogliptin dosages ) . Main outcome measures : The primary efficacy endpoint was the change in HbA1c from the baseline value at week 12 of treatment . Safety endpoints were the occurrence of adverse events , vital sign measurements , physical examination and ECG findings , and laboratory test results recorded over the entire 52-week period . Results : HbA1c was dose-dependently reduced by alogliptin , and the changes versus baseline were statistically significant with all four dosages in comparison with both placebo and voglibose . In addition , changes in fasting plasma glucose and postpr and ial plasma glucose AUC0–2h values were significantly greater with all four dosages of alogliptin in comparison with placebo . The incidence of adverse events with alogliptin over 52 weeks was not dose-dependent and was lower than with voglibose . Hypoglycemia occurred infrequently and was generally rated as mild . Changes in body weight with alogliptin were minimal ( < 0.5 kg ) and not clinical ly meaningful . Conclusions : Alogliptin was well tolerated and dose-dependently improved glycemic parameters in patients with type 2 diabetes inadequately controlled on diet and exercise Abstract Objective : Type 2 diabetes in the elderly is an important and insufficiently studied public health problem . This study evaluated sitagliptin monotherapy in patients with type 2 diabetes aged ≥65 years . Research design and methods : This was a r and omized , double-blind , placebo-controlled , parallel-group study conducted at 52 sites in the United States . Patients were treated with once-daily sitagliptin ( 100 or 50 mg , depending on renal function ) or placebo for 24 weeks . Key endpoints included change from baseline in glycated hemoglobin ( HbA1c ) , 2-hour post-meal glucose ( 2-h PMG ) and fasting plasma glucose ( FPG ) at week 24 , and average blood glucose on treatment days 3 and 7 . Clinical trial registration : NCT00305604 . Results : Among r and omized patients ( N = 206 ) , mean age was 72 years and mean baseline HbA1c was 7.8 % . At week 24 , HbA1c decreased by 0.7 % , 2-h PMG by 61 mg/dL , and FPG by 27 mg/dL in sitagliptin-treated patients compared with placebo ( all p < 0.001 ) . On day 3 of treatment , mean average blood glucose was decreased from baseline by 20.4 mg/dL in sitagliptin-treated patients compared with placebo ( p < 0.001 ) . In subgroups defined by baseline HbA1c < 8.0 % ( n = 132 ) , ≥8.0 % to < 9.0 % ( n = 42 ) , and ≥9.0 % ( n = 18 ) , the placebo-adjusted reductions in HbA1c with sitagliptin treatment were 0.5 % , 0.9 % , and 1.6 % , respectively . Patients in the sitagliptin and placebo groups had similar rates of adverse events overall ( 46.1 % and 52.9 % , respectively ) ; serious adverse events were reported in 6.9 % and 13.5 % , respectively . No adverse events of hypoglycemia were reported . Potential study limitations include a relatively small number of patients with more severe hyperglycemia ( HbA1c ≥9.0 % ) and the exclusion of patients with severe renal insufficiency . Conclusion : In this study , sitagliptin treatment significantly and rapidly improved glycemic measures and was well tolerated in patients aged ≥65 years with type 2 diabetes Abstract Objective : Glycaemic control in patients with type 2 diabetes ( T2DM ) is often not achieved or not sustained using monotherapy such as metformin , necessitating the addition of other antihyperglycaemic agents . Linagliptin , a dipeptidyl peptidase-4 inhibitor , is licensed for 5 mg once-daily dosing . As metformin is administered twice daily , a fixed-dose combination of these compounds would require twice-daily administration of linagliptin . This study evaluated whether 2.5 mg twice-daily dosing of linagliptin has comparable efficacy and safety to 5 mg once-daily dosing when given in addition to metformin twice daily in patients with inadequate glycaemic control . Methods : A total of 491 T2DM patients with glycated haemoglobin ( HbA1c ) 7.0–10.0 % were r and omised ( 5:5:1 ) to double-blind treatment with linagliptin 2.5 mg twice daily , 5 mg once daily or placebo , respectively , in addition to continuing metformin twice daily ( ≥1500 mg/day or maximally tolerated dose ) . The primary endpoint was change from baseline in HbA1c after 12 weeks . Clinical Trials.gov , NCT01012037 . Results : Mean baseline HbA1c for all patients was 7.97 % . After 12 weeks , linagliptin 2.5 mg twice daily and 5 mg once daily both significantly reduced HbA1c ( placebo-adjusted changes from baseline −0.74 % ( 95 % CI −0.97 , −0.52 ) and −0.80 % ( 95 % CI −1.02 , −0.58 ) , respectively , both p < 0.0001 ) . The treatment difference ( twice daily - once daily ) between the linagliptin regimens was 0.06 ( 95 % CI −0.07 , 0.19 ) , the upper bound of which was less than the predefined noninferiority margin ( 0.35 % ) . The overall incidence of adverse events with linagliptin 2.5 mg twice daily , 5 mg once daily and placebo was 43.0 % , 34.8 % , and 38.6 % respectively . Hypoglycaemia was rare ( 3.1 % with linagliptin 2.5 mg twice daily , 0.9 % with 5 mg once daily , 2.3 % with placebo ) with no severe episodes . Study limitations include duration , patient population ( mainly white ) and absence of postpr and ial glucose data . Conclusions : Linagliptin 2.5 mg twice daily had non-inferior HbA1c-lowering effects after 12 weeks compared to 5 mg once daily , with comparable safety and tolerability , in T2DM patients inadequately controlled with metformin . Trial registration : Clinical Trials.gov identifier : NCT01012037 This 24-week double-blind , r and omized , multicenter , placebo-controlled , parallel-group study was performed in 632 drug-naïve patients with type 2 diabetes to assess efficacy and tolerability of vildagliptin ( 50 mg qd , 50 mg bid , or 100 mg qd ) . HbA1c decreased modestly in patients receiving placebo ( Delta=-0.3+/-0.1 % ) and to a significantly greater extent in patients receiving vildagliptin 50 mg qd ( Delta=-0.8+/-0 .1 % ) , 50 mg bid ( Delta=-0.8+/-0.1 % ) , or 100 mg qd ( Delta=-0.9+/-0.1 % , p<0.01 for all groups VS . placebo ) from an average baseline of 8.4 % . In patients diagnosed > or=3 months before enrollment , HbA1c increased with placebo ( Delta=+0.2+/-0.2 % ) and between-treatment differences ( vildagliptin-placebo ) were -0.8+/-0.2 % ( p<0.001 ) , -0.7+/-0.2 % ( p=0.003 ) , and -0.9+/-0.2 % ( p<0.001 ) with vildagliptin 50 mg qd , 50 mg bid , and 100 mg qd , respectively . There was no apparent dose-response in the overall population ; however , in patients with high baseline HbA1c , there were greater reductions with either 100 mg dose regimen ( Delta=-1.3+/-0.2 % and -1.4+/-0.2 % ) compared to 50 mg qd ( Delta=-0.8+/-0.1 % ) . Body weight decreased modestly in all groups ( by 0.3 to 1.8 kg ) . The incidence of adverse events was similar across all groups and < or=1.2 % of patients in any treatment group reported mild hypoglycemia . In conclusion , vildagliptin monotherapy decreases HbA1c in drug-naïve patients without weight gain and is well tolerated with minimal hypoglycemia AIMS To assess efficacy and safety of sitagliptin , a dipeptidyl peptidase-4 inhibitor , in combination therapy with metformin ( ≥1500 mg/day ) and pioglitazone ( ≥30 mg/day ) in patients with type 2 diabetes ( T2DM ) with inadequate glycemic control ( hemoglobin A1c [ HbA1c ] ≥7.5 % and ≤11 % ) . METHODS This placebo-controlled , double-blind study included 313 patients , mean baseline HbA1c=8.7 % , who were r and omized to receive sitagliptin 100 mg/day or placebo for 26 weeks . RESULTS The addition of sitagliptin led to significant ( P<.001 ) mean changes from baseline relative to placebo in HbA1c ( -0.7 % ) , fasting plasma glucose ( -1.0 mmol/L ) , and 2-h post-meal glucose ( -2.2 mmol/L ) . In patients with baseline HbA1c ≥9.0 % , mean changes from baseline in HbA1c were -1.6 % and -0.8 % for the sitagliptin and placebo groups , respectively ( between-group difference -0.8 % ; P<.001 ) . The incidences of reported adverse events were generally similar between the treatment groups . Incidences of symptomatic hypoglycemia were 7/157 [ 4.5 % ] and 6/156 [ 3.8 % ] in the sitagliptin and placebo groups , respectively ( P=.786 ) . Two patients , both in the placebo group , experienced an episode of hypoglycemia that required non-medical assistance . CONCLUSIONS In this 26-week study , addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated AIMS To examine the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in persons with Type 2 diabetes mellitus inadequately controlled [ HbA(1c ) 53 - 86 mmol/mol ( 7.0 - 10.0 % ) ] by metformin and sulphonylurea combination treatment . METHODS A multi-centre , 24-week , r and omized , double-blind , parallel-group study in 1058 patients comparing linagliptin ( 5 mg once daily ) and placebo when added to metformin plus sulphonylurea . The primary endpoint was the change in HbA(1c ) after 24 weeks . RESULTS At week 24 , the linagliptin placebo-corrected HbA(1c ) adjusted mean change from baseline was -7 mmol/mol ( -0.62 % ) [ 95 % CI -8 to -6 mmol/mol ( -0.73 to -0.50 % ) ; P < 0.0001 ] . More participants with baseline HbA(1c ) ≥ 53 mmol/mol ( ≥ 7.0 % ) achieved an HbA(1c ) < 53 mmol/mol ( < 7.0 % ) with linagliptin compared with placebo ( 29.2 % vs. 8.1 % , P < 0.0001 ) . Fasting plasma glucose was reduced with linagliptin relative to placebo ( -0.7 mmol/l , 95 % CI -1.0 to -0.4 ; P<0.0001 ) . Improvements in homeostasis model assessment of β-cell function were seen with linagliptin ( P<0.001 ) . The proportion of patients who reported a severe adverse event was low in both groups ( linagliptin 2.4 % ; placebo 1.5 % ) . Symptomatic hypoglycaemia occurred in 16.7 and 10.3 % of the linagliptin and placebo groups , respectively . Hypoglycaemia was generally mild or moderate ; severe hypoglycaemia was reported in 2.7 and 4.8 % of the participants experiencing hypoglycaemic episodes in the linagliptin and placebo groups , respectively . No significant weight changes were noted . CONCLUSIONS In patients with Type 2 diabetes , adding linagliptin to metformin given in combination with a sulphonylurea significantly improved glycaemic control and this was well tolerated . Linagliptin could provide a valuable treatment option for individuals with inadequate glycaemic control despite ongoing combination therapy with metformin and a sulphonylurea The aim of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor , sitagliptin , in patients with type 2 diabetes who have inadequate glycaemic control on diet and exercise . In a r and omised , double-blind , placebo- and active-controlled study , 743 patients with type 2 diabetes and a mean baseline HbA(1c ) of 7.9 % were r and omised to receive one of six treatments for 12 weeks : placebo , sitagliptin 5 , 12.5 , 25 or 50 mg b.i.d . , or glipizide 5 mg/day ( electively titrated up to 20 mg/day ) . At week 12 , treatment with sitagliptin at all doses tested led to a significant ( p < 0.001 ) reduction in HbA(1c ) relative to placebo , with the largest reductions occurring in the 50-mg b.i.d . group . The placebo-subtracted differences in HbA(1c ) for the sitagliptin dose groups ranged from -0.38 % to -0.77 % in a dose-dependent manner , and -1.00 % in the glipizide group . Sitagliptin also produced significant reductions in fasting plasma glucose and mean daily glucose across the dose range studied . Sitagliptin treatment was well tolerated and result ed in no significant weight change relative to placebo . There was a modest weight gain observed with glipizide treatment relative to placebo . Hypoglycaemia adverse experiences were reported with the highest incidence in the glipizide group ( 17 % ) compared with the placebo ( 2 % ) or sitagliptin groups ( 0 - 4 % , not dose-dependent ) . In summary , in this study sitagliptin improved glycaemic control , with 50 mg b.i.d . being the most effective dose , and was generally well-tolerated in patients with type 2 diabetes BACKGROUND Some patients with type 2 diabetes mellitus ( T2DM ) receiving monotherapy with a sulfonylurea ( SU ) are unable to meet recommended glycemic targets over the long term and require additional pharmacologic agents to maintain glycemic control . This study was design ed to assess the utility of adjunctive therapy with the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in patients with T2DM inadequately controlled with SU monotherapy . OBJECTIVE To assess the efficacy and tolerability of linagliptin as add-on therapy in patients with inadequately controlled T2DM despite background therapy with an SU . METHODS In this Phase III , multicenter , r and omized , double-blind , placebo-controlled trial , patients with inadequately controlled T2DM on SU monotherapy were r and omly assigned to receive treatment with linagliptin 5 mg once daily ( n = 161 ) or placebo ( n = 84 ) for 18 weeks . The primary end point was the mean change in hemoglobin ( Hb ) A(1c ) from baseline to week 18 , evaluated using ANCOVA . Tolerability was assessed using laboratory analysis , spontaneous reporting , and physical examination and interview . RESULTS Mean baseline characteristics were similar in the linagliptin and placebo groups . Linagliptin treatment was associated with a placebo-corrected mean ( 95 % CI ) change in HbA(1c ) from baseline ( 8.6 % ) to 18 weeks of -0.47 % ( -0.70 to -0.24 ; P < 0.0001 ) . Patients in the linagliptin group were more likely compared with placebo to achieve the HbA(1c ) target level of < 7.0 % after 18 weeks of treatment ( 15.2 % vs 3.7 % , respectively ; odds ratio [ OR ] = 6.5 ; 95 % CI , 1.7 - 24.8 ; P = 0.007 ) . Similarly , patients in the linagliptin group were more likely to achieve an HbA(1c ) reduction of ≥0.5 % compared with those in the placebo group ( 57.6 % vs 22.0 % ; OR = 5.1 , 95 % CI 2.7 - 9.6 ; P < 0.0001 ) . The overall frequency of adverse events was similar between the linagliptin and placebo groups ( 42.2 % vs 42.9 % ) . The incidences of hypoglycemic events were not significantly different between the 2 groups ( 5.6 % vs 4.8 % ) , and none of the hypoglycemic episodes were assessed as severe by the investigator . The difference in the changes in mean body weight was not significant ( + 0.43 vs -0.01 kg ; P = 0.12 ) . CONCLUSIONS The addition of linagliptin to SU therapy for 18 weeks in these patients with T2DM was associated with statistically significant and clinical ly meaningful reductions in HbA(1c ) compared with placebo . The overall tolerability of linagliptin was similar to that of placebo , with a low risk for hypoglycemia and no significant weight gain . These findings support the use of linagliptin as adjunctive therapy in patients with T2DM inadequately controlled on SU monotherapy . Clinical Trials.gov identifier : NCT00819091 ABSTRACT Objective : Sitagliptin , an oral , potent , and selective dipeptidyl peptidase-4 ( DPP‑4 ) inhibitor was evaluated as once-daily monotherapy in a 12-week r and omized , double-blind , placebo-controlled , parallel group , dose-ranging study . Additionally , the glycemic response to sitagliptin 100 mg daily was evaluated as a once-daily ( 100 mg once-daily ) or twice-daily ( 50 mg twice-daily ) dosing regimen . Research design and methods : In a multinational , double-blind , r and omized , placebo-controlled , parallel-group , dose-range finding study , 555 patients , 23–74 years of age , with HbA1c of 6.5–10.0 % were r and omized to one of five treatment groups : placebo , sitagliptin 25 , 50 or 100 mg once-daily , or sitagliptin 50 mg twice-daily for 12 weeks . The efficacy analysis was based on the all- patients -treated population using an ANCOVA model . Results : Mean baseline HbA1c ranged from 7.6 to 7.8 % across treatment groups , with 29 % of all patients with values ≤ 7 % . After 12 weeks , treatment with all doses of sitagliptin significantly ( p < 0.05 ) reduced HbA1c by –0.39 to –0.56 % and fasting plasma glucose by –11.0 to –17.2 mg/dLrelative to placebo , with the greatest reduction observed in the 100-mg once-daily group . Mean daily glucose was significantly ( p < 0.05 ) reduced by –14.0 to –22.6 mg/dL with all doses of sitagliptin relative to placebo . HOMA‑β was significantly ( p < 0.05 ) increased by 11.3–15.2 with all sitagliptin doses relative to placebo . QUICKI and HOMA‑IR were not significantly changed with sitagliptin treatment . There were no significant differences observed between the sitagliptin 100 mg once-daily and 50 mg twice-daily groups for any parameter . For sitagliptin , the incidence of adverse events of hypoglycemia was low , with one event in each of the 25- and 50-mg once-daily and 50-mg twice-daily treatment groups and two events in the 100 mg once-daily treatment group . There was no mean change in body weight with sitagliptin relative to placebo . Study duration may be a limitation because the extent of the glycemic response and the safety and tolerability may not have been fully eluci date d in this 12-week study . Conclusion : Sitagliptin monotherapy improved indices of glycemic control compared to placebo and was generally well-tolerated in patients with type 2 diabetes . The glycemic response to treatment with sitagliptin 100 mg/day was similar between the sitagliptin 100-mg once-daily and 50-mg twice-daily dose regimens AIM To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [ haemoglobin A(1c ) ( HbA(1c ) ) 7 - 11 % ] on metformin monotherapy . METHODS Patients ( n = 273 ) on metformin ( > /=1500 mg/day ) were r and omized to receive the addition of once-daily placebo , sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks . The efficacy analysis was based on the all- patients -treated population using an analysis of co-variance with change in HbA(1c ) from baseline as the primary endpoint . RESULTS The mean baseline HbA(1c ) was 7.7 % for the entire cohort . After 18 weeks , both active add-on therapies led to greater improvements in HbA(1c ) from baseline : -0.73 % for sitagliptin ( p < 0.001 vs. placebo ) and -0.79 % for rosiglitazone compared with -0.22 % for placebo . No difference was observed between the sitagliptin and rosiglitazone treatments ( 0.06 % [ 95 % confidence interval ( CI ) : -0.14 to 0.25 ] ) . The proportion of patients achieving an HbA(1c ) < 7 % was greater with sitagliptin ( 55 % ) and rosiglitazone ( 63 % ) compared with placebo ( 38 % ) . Body weight increased from baseline with rosiglitazone ( 1.5 kg ) compared with body weight reduction with sitagliptin ( -0.4 kg ) and placebo ( -0.8 kg ) . The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg ( 95 % CI : 1.3 - 2.5 ) . In a prespecified analysis , the proportion of patients experiencing a greater than 3-kg increase in body weight was 21 % in the rosiglitazone group compared with 2 % in both the sitagliptin and placebo groups . Both active treatments were generally well tolerated , with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo . CONCLUSIONS In this 18-week study , the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy . Treatment with sitagliptin produced similar reductions in HbA(1c ) compared with the addition of rosiglitazone BACKGROUND The present study was conducted to evaluate the efficacy , safety and tolerability of sitagliptin added to ongoing metformin therapy in Chinese patients with type 2 diabetes ( T2DM ) who failed to achieve adequate glycemic control with metformin monotherapy . METHODS After a metformin titration/stabilization period and a 2-week , single-blind , placebo run-in period , 395 Chinese patients with T2DM aged 25 - 77 years ( baseline HbA1c 8.5 % ) were r and omized ( 1:1 ) to double-blind placebo or sitagliptin 100 mg q.d . added to ongoing open-label metformin ( 1000 or 1700 mg/day ) for 24 weeks . RESULTS Significant ( P < 0.001 ) changes from baseline in HbA1c ( -0.9 % ) , fasting plasma glucose ( -1.2 mmol/L ) , and 2-h post-meal plasma glucose ( -1.9 mmol/L ) were seen with sitagliptin compared with placebo . There were no significant differences between sitagliptin and placebo in the incidence of hypoglycemia or gastrointestinal adverse events . A small decrease from baseline body weight was observed in the placebo group compared with no change in the sitagliptin group ( between-group difference 0.5 kg ; P=0.018 ) . CONCLUSIONS The addition of sitagliptin 100 mg to ongoing metformin therapy significantly improved glycemic control and was generally well tolerated in Chinese patients with T2DM who had inadequate glycemic control on metformin alone BACKGROUND New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes ( T2D ) , a progressive disorder that often requires combination therapy . The present study assessed the efficacy and safety of sitagliptin as add-on therapy to metformin and rosiglitazone in patients with T2D . METHODS The present study was a r and omized double-blind placebo-controlled parallel-group 54-week study conducted at 41 sites across North and South America , Europe , and Asia in 278 patients with HbA1c ranging from ≥7.5 % to ≤11.0 % despite ongoing combination therapy with metformin ( ≥1500 mg/day ) and rosiglitazone ( ≥4 mg/day ) . Patients were r and omized ( 2:1 ) to receive sitagliptin 100 mg or placebo once daily . The main outcome measure was change from baseline in HbA1c at Week 18 . RESULTS Mean baseline HbA1c was 8.8 % . The mean placebo-adjusted change from baseline in HbA1c with sitagliptin treatment was -0.7 % ( P < 0.001 ) at Week 18 and -0.8 % ( P < 0.001 ) at Week 54 . There were also significant ( P < 0.001 ) reductions in 2-h post-meal glucose and fasting plasma glucose compared with placebo at Weeks 18 and 54 . Significantly higher proportions of sitagliptin- than placebo-treated patients had HbA1c<7.0 % at Weeks 18 ( 22 % vs 9 % ; P = 0.003 ) and 54 ( 26 % vs 14 % ; P = 0.015 ) . Changes in body weight and the rates of adverse events overall , hypoglycemia , and gastrointestinal adverse events were similar in the sitagliptin and placebo groups during the 54-week study . CONCLUSIONS In patients with T2D , the addition of sitagliptin for 54 weeks to ongoing therapy with metformin and rosiglitazone improved glycemic control and was generally well tolerated compared with placebo BACKGROUND Type 2 diabetes mellitus ( T2DM ) treatment generally requires multiple antihyperglycemic agents . When diet , exercise , and treatment with sulfonylurea and metformin do not achieve glycemic goals , several options are available . The present study evaluated the efficacy and tolerability of sitagliptin 100 mg/day added to therapy with sulfonylurea and metformin . METHODS Patients with HbA1c ≥7.5 % and ≤10.5 % while on a sulfonylurea and metformin were r and omized 1 : 1 to sitagliptin 100 mg/day or placebo for 24 weeks . At Week 24 , patients in the placebo group switched to pioglitazone 30 mg/day and both groups continued treatment for another 30 weeks . RESULTS Of 427 patients r and omized , 339 ( 79.4 % ) completed the study . At Week 24 , significantly greater ( P < 0.001 ) mean reductions from baseline were seen in the sitagliptin versus placebo group for HbA1c ( -0.84 % vs -0.16 % , respectively ) , 2-h post-meal glucose ( -2.0 vs -0.2 mmol/L , respectively ) and fasting plasma glucose ( -0.7 vs 0.3 mmol/L , respectively ) . At Week 54 , improvements in glycemic control continued . At Week 24 , the incidence of adverse events ( AEs ) was numerically greater with sitagliptin than placebo , primarily because of a higher incidence of hypoglycemia . At Week 54 , the incidence of AEs was similar in both groups , primarily because of a higher incidence of hypoglycemia and edema in the placebo/pioglitazone group after Week 24 . The only meaningful change in body weight was an increase in the placebo/pioglitazone group at Week 54 . CONCLUSIONS In this study , sitagliptin 100 mg/day was generally well tolerated and provided improvement in glycemic control when added to the combination of sulfonylurea and metformin in patients with T2DM Abstract Objective : To examine the effects of canagliflozin , a sodium glucose co-transporter 2 inhibitor that lowers blood glucose by increasing urinary glucose excretion ( UGE ) , on asymptomatic bacteriuria and urinary tract infections ( UTIs ) . Research design and methods : In a r and omized , double-blind , placebo-controlled , multicenter , dose-ranging phase 2 study , subjects with type 2 diabetes with inadequate glycemic control while receiving metformin were enrolled and r and omized to one of seven arms – placebo ; canagliflozin doses 50 mg , 100 mg , 200 mg , 300 mg daily , or 300 mg twice daily ; and sitagliptin 100 mg daily – for 12 weeks . Clinical trial registration : Clinical Trials.gov identifier : NCT00642278 . Results : Canagliflozin increased renal glucose excretion by 35.4–61.6 mg/mg creatinine in the five dose groups . In the placebo group renal glucose excretion was increased by 1.9 mg/mg creatinine , and in the sitagliptin group it decreased by 1.9 mg/mg creatinine . Asymptomatic bacteriuria ( ASB ) were present in 6.4 % of canagliflozin and 6.5 % of placebo/sitagliptin ( control ) subjects at r and omization and , at 12 weeks , in 7.7 % and 6.3 % of subjects , respectively ( odds ratio [ OR ] 1.23 ; 95 % confidence interval [ CI ] , 0.45–3.89 ) . For subjects with initially negative urine cultures at baseline , 3 out of 82 ( 3.7 % ) who received controls and 10 out of 207 ( 4.8 % ) who received canagliflozin developed bacteriuria ( p = 0.76 ) at week 12 . There were 21 adverse event ( AE ) reports of UTI ; 16 ( 5.0 % ) in canagliflozin subjects and 5 ( 3.8 % ) in control subjects ( OR 1.31 ; 95 % CI , 0.45–4.68 ) . Conclusions : In this trial , when compared with control subjects , canagliflozin increased UGE but was not associated with increased bacteriuria or AE reports of UTI . However , further studies enrolling larger numbers of subjects with longer term exposure to canagliflozin will be necessary to more fully underst and the impact of this agent on the risk of developing UTI AIMS To evaluate the efficacy and safety of alogliptin , a new dipeptidyl peptidase-4 inhibitor , for 26 weeks at once-daily doses of 12.5 and 25 mg in combination with metformin in patients whose HbA(1c ) levels were inadequately controlled on metformin alone . METHODS AND PATIENTS Patients with type 2 diabetes and inadequate glycaemic control ( HbA(1c ) 7.0 - 10.0 % ) were r and omised to continue a stable daily metformin dose regimen ( > or = 1500 mg ) plus the addition of placebo ( n = 104 ) or alogliptin at once-daily doses of 12.5 ( n = 213 ) or 25 mg ( n = 210 ) . HbA(1c ) , insulin , proinsulin , C-peptide and fasting plasma glucose ( FPG ) concentrations were determined over a period of 26 weeks . RESULTS Alogliptin at either dose produced least squares mean ( SE ) decreases from baseline in HbA(1c ) of -0.6 (0.1)% and in FPG of -17.0 ( 2.5 ) mg/dl [ -1.0 ( 0.1 ) mmol/l ] , decreases that were significantly ( p < 0.001 ) greater than those observed with placebo . The between treatment differences ( alogliptin - placebo ) in FPG reached statistical significance ( p < 0.001 ) as early as week 1 and persisted for the duration of the study . Overall , adverse events ( AEs ) observed with alogliptin were not substantially different from those observed with placebo . This includes low event rates for gastrointestinal side effects and hypoglycaemic episodes . There was no dose-related pattern of AE reporting between alogliptin groups and few serious AEs were reported . CONCLUSION Alogliptin is an effective and safe treatment for type 2 diabetes when added to metformin for patients not sufficiently controlled on metformin monotherapy AIM To assess the efficacy and safety of a range of doses of a systemic , partial , glucokinase activator , PF-04937319 , as add-on therapy to metformin , in patients with type 2 diabetes mellitus ( T2DM ) . METHODS Patients were r and omized to once-daily PF-04937319 doses of 10 , 50 , 100 mg , or matching placebo ( Study B1621002 ) ; or PF-04937319 doses of 3 , 20 , 50 , 100 mg , or matching placebo ( Study B1621007 ) . Titrated glimepiride ( Study B1621002 ) or sitagliptin ( Study B1621007 ) were included in a double-dummy manner . The primary measure was change from baseline in glycated haemoglobin ( HbA1c ) at week 12 . Key secondary measures included other glycaemic variables and safety and tolerability . RESULTS In the 639 patients r and omized , the minimally efficacious PF-04937319 dose was identified as 50 mg once daily . At the highest PF-04937319 dose tested ( 100 mg ) , on average , a clinical ly significant reduction in HbA1c [ -4.94 or -5.11 mmol/mol ( -0.45 or -0.47 % ) , placebo-adjusted ] , which was similar to that achieved with sitagliptin [ -4.69 mmol/mol ( -0.43 % ) ] but lower than that achieved with titrated glimepiride [ -9.07 mmol/mol ( -0.83 % ) ] , was observed . At this dose , the effect on fasting plasma glucose was not consistent between the two studies ( Study B1621002 vs Study B1621007 : placebo-adjusted mean change of -0.83 vs + 0.50 mmol/l ) . PF-04937319 was well tolerated at doses up to 100 mg . Hypoglycaemia was reported in 2.5 % of patients ( on placebo ) , 5.1 % of patients ( on PF-04937319 100 mg ) , 1.8 % of patients ( on sitagliptin ) and 34.4 % of patients ( on titrated glimepiride ) . CONCLUSIONS In patients on metformin monotherapy , the addition of a 100-mg dose of PF-04937319 improved glycaemic control and was well tolerated BACKGROUND We aim ed to investigate the efficacy and tolerability of empagliflozin , an oral , potent , and selective inhibitor of sodium-glucose co-transporter 2 , in patients with type 2 diabetes who had not received drug treatment in the preceding 12 weeks . METHODS In our multicentre , r and omised , placebo-controlled , phase 3 trial , we enrolled adults ( aged ≥18 years ) who had not received oral or injected anti-diabetes treatment in the previous 12 weeks . Eligible patients had HbA1c concentrations of 7 - 10 % . We r and omly allocated patients ( 1:1:1:1 ) with a computer-generated r and om sequence , stratified by region , HbA1c , and estimated glomerular filtration rate at screening , to placebo , empagliflozin 10 mg , empagliflozin 25 mg , or sitagliptin 100 mg once daily for 24 weeks . Patients and investigators were masked to treatment assignment . The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in all r and omly allocated patients who were treated with at least one dose of study drug and had a baseline HbA1c value . This study is completed and registered with Clinical Trials.gov , number NCT01177813 . FINDINGS Between Aug 12 , 2010 , and March 19 , 2012 , we r and omly allocated 228 patients to receive placebo , 224 to receive empagliflozin 10 mg , 224 to receive empagliflozin 25 mg , and 223 to receive sitagliptin . Compared with placebo , adjusted mean differences in change from baseline HbA1c at week 24 were -0·74 % ( 95 % CI -0·88 to -0·59 ; p<0·0001 ) for empagliflozin 10 mg , -0·85 % ( -0·99 to -0·71 ; p<0·0001 ) for empagliflozin 25 mg , and -0·73 % ( -0·88 to -0·59 ; p<0·0001 ) for sitagliptin . 140 ( 61 % ) patients in the placebo group reported adverse events ( four [ 2 % ] severe and six [ 3 % ] serious ) , as did 123 ( 55 % ) patients in the empagliflozin 10 mg group ( eight [ 4 % ] severe and eight [ 4 % ] serious ) , 135 ( 60 % ) patients in the empagliflozin 25 mg group ( seven [ 3 % ] severe and five [ 2 % ] serious ) , and 119 ( 53 % ) patients in the sitagliptin group ( five [ 2 % ] severe and six [ 3 % ] serious ) . INTERPRETATION Empagliflozin provides a tolerable and efficacious strategy to reduce HbA1c in patients with type 2 diabetes who had not previously received drug treatment . FUNDING Boehringer Ingelheim and Eli Lilly AIM To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 ( DPP-4 ) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control . METHODS This 24-week , r and omized , placebo-controlled , double-blind , parallel-group study was carried out in 82 centres in 10 countries . Patients with HbA1c levels of 7.0 - 10.0 % on metformin and a maximum of one additional antidiabetes medication , which was discontinued at screening , continued on metformin ≥1500 mg/day for 6 weeks , including a placebo run-in period of 2 weeks , before being r and omized to linagliptin 5 mg once daily ( n = 524 ) or placebo ( n = 177 ) add-on . The primary outcome was the change from baseline in HbA1c after 24 weeks of treatment , evaluated with an analysis of covariance ( ANCOVA ) . RESULTS Mean baseline HbA1c and fasting plasma glucose ( FPG ) were 8.1 % and 9.4 mmol/l , respectively . Linagliptin showed significant reductions vs. placebo in adjusted mean changes from baseline of HbA1c ( -0.49 vs. 0.15 % ) , FPG ( -0.59 vs. 0.58 mmol/l ) and 2hPPG ( -2.7 vs. 1.0 mmol/l ) ; all p < 0.0001 . Hypoglycaemia was rare , occurring in three patients ( 0.6 % ) treated with linagliptin and five patients ( 2.8 % ) in the placebo group . Body weight did not change significantly from baseline in both groups ( -0.5 kg placebo , -0.4 kg linagliptin ) . CONCLUSIONS The addition of linagliptin 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin result ed in a significant and clinical ly meaningful improvement in glycaemic control without weight gain or increased risk of hypoglycaemia The efficacy and safety of sitagliptin as monotherapy were evaluated in Chinese , Indian , and Korean patients with type 2 diabetes inadequately controlled by diet and exercise . In a r and omized , placebo-controlled , double-blind , 18-week trial , 530 patients with HbA(1c ) > or=7.5 % and < or=11.0 % ( mean baseline 8.7 % ) received sitagliptin 100 mg once daily or placebo . Compared with placebo , sitagliptin significantly ( p<0.001 ) reduced mean HbA(1c ) ( -1.0 % ) , fasting plasma glucose ( -1.7 mmol/L ) , and 2-h postpr and ial glucose ( -3.1 mmol/L ) , and a significantly ( p<0.001 ) greater proportion of sitagliptin-treated versus placebo-treated patients achieved HbA(1c ) < 7 % ( 20.6 % versus 5.3 % , respectively ) at study end . Efficacy of sitagliptin was demonstrated in each country . Sitagliptin was generally well-tolerated . Clinical adverse events ( AEs ) were reported in 23.3 % and 15.2 % of sitagliptin-treated and placebo-treated patients , respectively . The difference was primarily due to increased gastrointestinal AEs in the sitagliptin group , most of which were mild and resolved on study drug . Serious AEs , discontinuations due to AEs , and drug-related AEs occurred with a low incidence in both groups . No hypoglycemia was reported . In conclusion , in this study , sitagliptin monotherapy for 18 weeks significantly improved glycemic control and was well-tolerated in patients with type 2 diabetes from China , India , and Korea AIM To investigate the efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled with metformin . METHODS This was a 24-week , r and omized , double-blind , placebo-controlled study . Patients with T2DM ( N = 438 ) with haemoglobin A1c ( HbA1c ) of 7.0 - 10.0 % and fasting plasma glucose ( FPG ) < 15 mmol/l ( < 270 mg/dl ) were r and omized ( 1 : 1 : 1 ) to vildagliptin 50 mg bid , vildagliptin 50 mg qd or placebo in addition to metformin . RESULTS The treatment groups were well balanced at baseline [ mean HbA1c , 8.0 % , FPG , 8.8 mmol/l ( 158 mg/dl ) ; body mass index , 25.5 kg/m(2 ) ] . The adjusted mean change ( AMΔ ) in HbA1c at endpoint was -1.05 ± 0.08 % , -0.92 ± 0.08 % and -0.54 ± 0.08 % in patients receiving vildagliptin 50 mg bid , 50 mg qd and placebo , respectively . The between-treatment difference ( vildagliptin 50 mg bid-placebo ) was -0.51 ± 0.11 % , p < 0.001 . A greater proportion of vildagliptin-treated patients met at least one responder criterion ( 82.1 and 70.7 % ) compared to placebo-treated patients ( 60.4 % ) . The AMΔ at endpoint for FPG with vildagliptin 50 mg bid , -0.95 mmol/l ( -17.1 mg/dl ) ; 50 mg qd , -0.84 mmol/l ( -15.1 mg/dl ) was significantly different compared with the placebo -0.26 mmol/l ( -4.68 mg/dl ) ( p ≤ 0.001 ) . Adverse events ( AEs ) were reported as 34.2 , 36.5 and 37.5 % for patients receiving vildagliptin 50 mg bid , 50 mg qd or placebo , respectively . Two patients in the vildagliptin 50 mg qd and one in the placebo group reported serious AEs , which were not considered to be related to the study drug ; one incidence of hypoglycaemic event was reported in the vildagliptin 50 mg bid group . CONCLUSION Vildagliptin as add-on therapy to metformin improved glycaemic control and was well tolerated in Chinese patients who were inadequately controlled by metformin only To evaluate the efficacy and safety of saxagliptin as add‐on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of sitagliptin as an add-on to metformin therapy in patients with moderately severe ( hemoglobin A(1c ) > or= 8.0 % and < or= 11.0 % ) type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS This was a multinational , r and omized , placebo-controlled , parallel-group , double-blind study conducted in 190 patients with T2DM . After > or= 6 weeks of stable metformin monotherapy ( > or= 1500 mg/day ) , patients were r and omized to either the addition of sitagliptin 100 mg once daily or placebo to ongoing metformin for 30 weeks . MAIN OUTCOME MEASURES The primary efficacy endpoint was reduction in hemoglobin A(1c ) ( HbA(1c ) ) measured after 18 weeks of sitagliptin treatment . Key secondary endpoints included reduction in fasting plasma glucose ( FPG ) and 2-hour ( 2-h ) postpr and ial plasma glucose ( PPG ) at 18 weeks , and HbA(1c ) at 30 weeks . The proportion of patients meeting the goal of HbA(1c ) < 7.0 % was also analyzed . RESULTS Sitagliptin significantly reduced HbA(1c ) , FPG , and 2-h PPG , compared with placebo ( all p < 0.001 ) . The net improvement in HbA(1c ) was - 1.0 % at both 18 and 30 weeks , and a significantly greater proportion of patients treated with sitagliptin achieved HbA(1c ) < 7.0 % by the end of the study ( 22.1 % vs. 3.3 % , p < 0.001 ) . Sitagliptin was well-tolerated . Compared with placebo , sitagliptin had a neutral effect on body weight and did not significantly increase the risk of hypoglycemia or gastrointestinal adverse events . CONCLUSIONS Addition of sitagliptin 100 mg once daily to ongoing metformin therapy was well-tolerated and result ed in significant glycemic improvement in patients with moderately severe T2DM who were treated for 30 weeks AIM To investigate the efficacy and tolerability of vildagliptin , a potent and selective dipeptidyl peptidase-4 inhibitor , as add-on to glimepiride in Japanese patients with Type 2 diabetes mellitus ( T2DM ) who were inadequately controlled . METHODS This 12-week , r and omized , double-blind , placebo-controlled study compared vildagliptin 50 mg twice-daily ( n=102 ) with placebo ( n=100 ) when added to a stable dose of glimepiride ( > or=1mg/d ) . RESULTS Treatment groups were balanced at baseline ( glycosylated hemoglobin [ HbA(1c ) ] , 7.9 % ; fasting plasma glucose , 163.8 mg/dL ) . During treatment HbA(1c ) decreased progressively with vildagliptin , but remained unchanged with placebo . The adjusted mean change ( AMDelta ) at endpoint was -1.0+/-0.1 and -0.1+/-0.1 % in vildagliptin- and placebo-treated patients ( between-group Delta=-1.0+/-0.1 % , P<0.001 ) . A greater proportion of vildagliptin-treated patients had HbA(1c ) < or=6.5 % compared to placebo-treated patients ( 45 % vs. 3 % , P<0.001 ) . The AMDelta FPG was -20.9+/-2.8 mg/dL with vildagliptin compared to 6.3+/-2.8 mg/dL with placebo ( between-group Delta=-27.2+/-3.9 mg/dL , P<0.001 ) . Patients in vildagliptin and placebo groups reported similar incidences of adverse events ( AEs ) ( 59.8 % vs. 57.0 % ) , serious AEs ( 0 % vs. 2.0 % ) , suspected drug-related AEs ( 21.6 % vs. 23.0 % ) , and discontinuation due to AEs ( 1.0 % vs. 3.0 % ) . Hypogylcaemia was reported in two ( vildagliptin ) and one ( placebo ) patient . CONCLUSION Vildagliptin is effective and well tolerated as an add-on to glimepiride in Japanese patients with T2DM AIM To evaluate the efficacy and safety of alogliptin , a potent and highly selective dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy . METHODS After a 2-week screening period , adult patients 18 - 80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide ( open label ) plus placebo ( single blind ) . After the run-in period , patients were r and omly assigned to double-blind treatment with alogliptin 12.5 mg ( n = 203 ) , alogliptin 25 mg ( n = 198 ) , or placebo ( n = 99 ) for 26 weeks . The primary end-point was change from baseline to week 26 in glycosylated haemoglobin ( HbA1c ) . Secondary end-points included clinical response rates and changes in fasting plasma glucose , beta-cell function ( fasting proinsulin , insulin , proinsulin/insulin ratio , and C-peptide , and homeostasis model assessment beta-cell function ) , body weight , and safety end-points [ adverse events ( AEs ) , clinical laboratory tests , vital signs and electrocardiographic readings ] . RESULTS The study population had a mean age of 57 years and a mean disease duration of 8 years ; it was well balanced for gender ( 52 % women ) and was mainly white ( 71 % ) . The mean baseline HbA1c was approximately 8.1 % in each group . Significantly greater least squares ( LS ) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg ( -0.38 % ) and 25 mg ( -0.52 % ) vs. placebo ( + 0.01 % ; p < 0.001 ) , and more patients in the alogliptin 25-mg group had HbA1c levels < or = 7.0 % at week 26 ( 34.8 % , p = 0.002 ) vs. placebo ( 18.2 % ) . Proportionately more patients in the alogliptin 12.5 mg ( 47.3 % ) and 25 mg ( 50.5 % ) groups had an HbA1c reduction > or = 0.5 % from baseline compared with patients in the placebo group ( 26.3 % ; p < 0.001 ) . Minor improvements in individual markers of beta-cell function were seen with alogliptin , but no significant treatment group differences were noted relative to placebo . Minor LS mean changes in body weight were noted across groups ( placebo , -0.20 kg ; alogliptin 12.5 mg , + 0.60 kg ; alogliptin 25 mg , + 0.68 kg ) . AEs were reported for 63 - 64 % of patients receiving alogliptin and 54 % of patients receiving placebo . Few AEs were treatment limiting ( 2.0 - 2.5 % across groups ) , and serious AEs ( 2.0 - 5.6 % ) were infrequent , similar across groups , and generally considered not related to treatment . The incidences of hypoglycaemia for placebo , alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1 , 15.8 and 9.6 % respectively . CONCLUSIONS In patients with type 2 diabetes inadequately controlled by glyburide monotherapy , the addition of alogliptin result ed in clinical ly significant reductions in HbA1c without increased incidence of hypoglycaemia BACKGROUND This study determined the efficacy and safety of once-daily oral alogliptin in patients from mainl and China , Taiwan , and Hong Kong with type 2 diabetes mellitus . METHODS In this Phase 3 multicenter double-blind placebo-controlled 16-week trial , 506 patients were r and omized to receive once-daily alogliptin 25 mg or placebo : 185 in the monotherapy group , 197 in the add-on to metformin group , and 124 in the add-on to pioglitazone group . The primary efficacy variable was the change from baseline ( CFB ) in HbA1c at Week 16 ; other efficacy measures included CFB to Week 16 in fasting plasma glucose ( FPG ) , incidence of marked hyperglycemia ( FPG ≥11.1 mmol/L ) , and the incidence of clinical HbA1c ≤6.5 % ( 48 mmol/mol ) and ≤7.0 % ( 53 mmol/mol ) at Week 16 . Safety was assessed throughout the trial . RESULTS Alogliptin monotherapy provided a significantly greater decrease in HbA1c from baseline to Week 16 compared with placebo ( -0.58 % ; 95 % confidence interval [ CI ] -0.78 % , -0.37 % ; P < 0.001 ) . As an add-on to metformin or pioglitazone , alogliptin also significantly decreased HbA1c compared with placebo ( -0.69 % [ 95 % CI -0.87 % , -0.51 % ; P < 0.001 ] and -0.52 % [ 95 % CI -0.75 % , -0.28 % ; P < 0.001 ] , respectively ) . In any treatment group versus placebo , alogliptin led to greater decreases in FPG ( P ≤ 0.004 ) and a higher percentage of patients who achieved an HbA1c target of ≤6.5 % and ≤7.0 % ( P ≤ 0.003 ) . No weight gain was observed in any treatment group . A similar percentage of patients experienced drug-related , treatment-emergent adverse events in the alogliptin and placebo arms . Four and two patients in the alogliptin and placebo arms , respectively , experienced mild or moderate hypoglycemia . CONCLUSIONS Alogliptin 25 mg once daily reduced HbA1c and FPG and enhanced clinical response compared with placebo when used as monotherapy or as an add-on to metformin or pioglitazone . Therapy with alogliptin was well tolerated AIMS To evaluate the efficacy and safety of alogliptin added to metformin versus metformin monotherapy in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on metformin ( 500 or 750 mg/day ) + diet/exercise . METHODS In a r and omized , double-blind trial , 288 patients with type 2 diabetes mellitus T2DM received either 12.5 or 25 mg alogliptin once daily + metformin or placebo + metformin for 12 weeks . Thereafter , 276 patients continued on one of the two alogliptin dosages + metformin in an open-label extension for 40 weeks . The primary efficacy endpoint in the r and omized , double-blind phase was the change in HbA1c from baseline ( week 0 ) to the end of treatment ( week 12 ) . The primary endpoint during the long-term extension phase was adverse events . RESULTS After 12 weeks both dosages of alogliptin + metformin produced significantly greater changes from baseline in HbA1c than placebo ( metformin monotherapy : with changes in LS means - 0.55 and - 0.64 % vs. 0.22 % , respectively ; p < 0.0001 ) . Incidences of adverse effects were comparable between groups , with no increases in hypoglycaemia . Over 52 weeks , there were no safety or tolerability concerns with alogliptin when added to metformin . CONCLUSIONS Alogliptin 12.5 and 25 mg once daily was safe and effective when added to metformin ( 500 or 750 mg/day ) in Japanese patients with inadequately controlled type 2 diabetes on metformin alone BACKGROUND Despite the increasing prevalence of type 2 diabetes mellitus ( T2DM ) in Asia , clinical trials for glucose-lowering therapies are often dominated by Caucasian and /or Western population s. The present Phase III r and omized placebo-controlled double-blind , 24-week study evaluated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin added to metformin in Asian T2DM patients . METHODS In all , 306 patients ( n = 265 Chinese ; n = 24 Malaysian ; n = 17 Filipino ) , aged 18 - 80 years with HbA1c between ≥7.0 and ≤10.0 % and on metformin therapy were r and omized ( 2:1 ) to either linagliptin 5 mg daily or placebo added to metformin . Antidiabetes drugs other than metformin were washed out prior to r and omization . The primary endpoint was change in mean HbA1c from baseline after 24 weeks . RESULTS Baseline characteristics were well-matched between the groups ( overall mean [ ±SD ] HbA1c 8.0 ± 0.8 % ) . Adjusted mean ( ±SE ) HbA1c decreased in the linagliptin and placebo groups by -0.66 ± 0.05 and -0.14 ± 0.07 % , respectively ( placebo-corrected difference -0.52 ± 0.09 % ; 95 % confidence interval [ CI ] -0.70 , -0.34 ; P < 0.0001 ) . In patients with baseline HbA1c ≥8.5 % , the placebo-corrected decrease in HbA1c was -0.89 ± 0.17 % ( P < 0.0001 ) . Adverse events occurred in similar proportions in the linagliptin and placebo patients ( 27.3 % and 28.0 % , respectively ) and few were considered drug-related ( 2.4 % and 0.0 % , respectively ) . Hypoglycemia occurred in 1.0 % of patients in both groups . Linagliptin therapy was weight neutral . CONCLUSIONS Linagliptin 5 mg was efficacious and well tolerated over 24 weeks in Asian patients with T2DM inadequately controlled by metformin ABSTRACT Objectives : To evaluate the efficacy and safety of alogliptin in patients with type 2 diabetes inadequately controlled by therapy with a thiazolidinedione ( TZD ) . Research design and methods : In a multicenter , double-blind , placebo-controlled clinical study , 493 patients 18–80 years old with inadequate glycemic control after stabilization ( i.e. , glycosylated hemoglobin [ HbA1c ] 7.0–10.0 % ) despite ongoing treatment with a TZD were r and omly assigned ( 2:2:1 ) to treatment with pioglitazone plus alogliptin 12.5 mg , alogliptin 25 mg or placebo once daily . Concomitant therapy with metformin or sulfonylurea at pre study doses was permitted . Main outcome measures : The primary efficacy endpoint was change in HbA1c from baseline to Week 26 . Secondary endpoints included changes in fasting plasma glucose ( FPG ) and body weight , and incidences of marked hyperglycemia ( FPG ≥ 200 mg/dL [ 11.10 mmol/L ] ) and rescue for hyperglycemia . Results : Least squares ( LS ) mean change in HbA1c was significantly ( p < 0.001 ) greater for alogliptin 12.5 mg ( −0.66 % ) or 25 mg ( −0.80 % ) than for placebo ( −0.19 % ) . A significantly ( p ≤ 0.016 ) larger proportion of patients achieved HbA1c ≤ 7 % with alogliptin 12.5 mg ( 44.2 % ) or 25 mg ( 49.2 % ) than with placebo ( 34.0 % ) . LS mean decreases in FPG were significantly ( p = 0.003 ) greater with alogliptin 12.5 mg ( −19.7 mg/dL [ −1.09 mmol/L ] ) or 25 mg ( −19.9 mg/dL [ −1.10 mmol/L ] ) than with placebo ( −5.7 mg/dL [ −0.32 mmol/L ] ) . The percentage of patients with marked hyperglycemia was significantly ( p < 0.001 ) lower for alogliptin ( ≤25.0 % ) than placebo ( 44.3 % ) . The incidences of overall adverse events and hypoglycemia were similar across treatment groups , but cardiac events occurred more often with active treatment than placebo . Conclusions : Addition of alogliptin to pioglitazone therapy significantly improved glycemic control in patients with type 2 diabetes and was generally well tolerated . The study did not evaluate the effect of combination therapy on long-term clinical outcomes and safety . Clinical trial registration : NCT00286494 , clinical trials.gov ABSTRACT Objective : To evaluate the efficacy and safety of once-daily saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes ( T2D ) and inadequate glycemic control . Research design and methods : This study included a main treatment cohort ( MTC ) with 401 patients ( HbA1c ≥ 7 % and ≤10 % ) r and omized and treated with oral saxagliptin 2.5 , 5 , or 10 mg once daily or placebo for 24 weeks and a separate open-label cohort ( OLC ) with 66 patients ( HbA1c > 10 % and ≤12 % ) who received saxagliptin 10 mg once daily for 24 weeks . Primary endpoint was HbA1c change from baseline to week 24 . Secondary endpoints included change from baseline to week 24 in fasting plasma glucose ( FPG ) , proportion of patients achieving HbA1c < 7 % , and changes in postpr and ial glucose area-under-the-curve ( PPG-AUC ) . Efficacy analyses for continuous variables were performed using an ANCOVA model with last-observation-carried-forward methodology . Results : In the MTC , saxagliptin demonstrated statistically significant decreases in adjusted mean HbA1c changes from baseline ( mean , 7.9 % ) to week 24 ( −0.43 % , −0.46 % , −0.54 % ) for saxagliptin 2.5 , 5 , and 10 mg , respectively , vs. + 0.19 % for placebo ( all p < 0.0001 ) . Adjusted mean FPG was significantly reduced from baseline ( −15 , −9 , −17 mg/dL ) for saxagliptin 2.5 , 5 , and 10 mg , respectively , vs. + 6 mg/dL for placebo ( p = 0.0002 , p = 0.0074 , p < 0.0001 , respectively ) . More saxagliptin-treated patients achieved HbA1c < 7 % at week 24 ( 35 % [ p = NS ] , 38 % [ p = 0.0443 ] , 41 % [ p = 0.0133 ] ) for saxagliptin 2.5 , 5 , and 10 mg , respectively , than placebo ( 24 % ) . PPG-AUC was reduced for saxagliptin 2.5 , 5 , and 10 mg ( −6868 , −6896 , −8084 mg·min/dL , respectively ) vs. placebo ( −647 mg·min/dL ) with statistical significance demonstrated for saxagliptin 5 mg ( p = 0.0002 ) and 10 mg ( p < 0.0001 ) . HbA1c , FPG , and PPG-AUC reductions were also observed in the OLC at 24 weeks . In the MTC , adverse event frequency was similar across all study arms . No cases of confirmed hypoglycemia ( symptoms , with fingerstick glucose ≤50 mg/dL ) were observed in either cohort . Saxagliptin was not associated with weight gain . Study limitations included the lack of a control group for the OLC and the use of prespecified rescue criteria , which limited the exposure time during which patients could remain on their originally r and omized medication without the introduction of additional antihyperglycemic rescue treatment . Conclusions : Once-daily saxagliptin monotherapy for 24 weeks was generally well tolerated and demonstrated clinical ly meaningful reductions in key parameters of glycemic control vs. placebo . Trial Registration : Clinical Trials OBJECTIVE The objective of this study was to assess the efficacy and safety of triple therapy with saxagliptin add-on versus placebo add-on to dapagliflozin plus metformin in adults with type 2 diabetes . RESEARCH DESIGN AND METHODS Patients on stable metformin ( ≥1,500 mg/day ) for ≥8 weeks with glycated hemoglobin ( HbA1c ) 8.0–11.5 % ( 64–102 mmol/mol ) at screening received open-label dapagliflozin ( 10 mg/day ) plus metformin immediate release ( IR ) for 16 weeks . Patients with inadequate glycemic control ( HbA1c 7–10.5 % [ 53–91 mmol/mol ] ) were then r and omized to receive placebo ( n = 153 ) or saxagliptin 5 mg/day ( n = 162 ) in addition to background dapagliflozin plus metformin IR . The primary efficacy end point was change in HbA1c from baseline to week 24 . RESULTS There was a significantly greater reduction in HbA1c at 24 weeks with saxagliptin add-on ( –0.51 % [ –5.6 mmol/mol ] ) versus placebo ( –0.16 % [ –1.7 mmol/mol ] ) add-on to dapagliflozin plus metformin ( difference , –0.35 % [ 95 % CI –0.52 % to –0.18 % ] and –3.8 [ –5.7 to –2.0 mmol/mol ] , respectively ; P < 0.0001 ) . Reductions in fasting plasma glucose and 2-h postpr and ial glucose were similar between treatment arms . A larger proportion of patients achieved HbA1c < 7 % ( 53 mmol/mol ) with saxagliptin add-on ( 35.3 % ) versus placebo add-on ( 23.1 % ) to dapagliflozin plus metformin . Adverse events were similar between treatment groups . Episodes of hypoglycemia were infrequent in both treatment arms , and there were no episodes of major hypoglycemia . CONCLUSIONS Triple therapy with the addition of saxagliptin to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with type 2 diabetes inadequately controlled with dapagliflozin plus metformin |
2,149 | 24,100,749 | Sorafenib was associated with a higher risk of adverse effects than placebo .
The risk for grade 3 - 4 h and -foot skin reactions , rash or desquamation , diarrhea , and hypertension was much higher in the sorafenib treatment group .
These side effects could often be mitigated with appropriate treatment .
CONCLUSIONS Sorafenib was a moderately effective and safe oral drug for use in Child-Pugh A patients with unresectable HCC .
Sorafenib monotherapy is not recommended for treating intermediate-stage HCC . | BACKGROUND AND GOALS Several studies have demonstrated that sorafenib is effective in the treatment of unresectable hepatocellular carcinoma ( HCC ) .
We performed a systematic review of the efficacy and safety of sorafenib in Child-Pugh A patients with unresectable HCC .
The value of sorafenib treatment in different subgroups was examined . | PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising Objective : This study was performed to identify clinical predictors for better survival in patients with advanced hepatocellular carcinoma ( HCC ) under sorafenib treatment . Methods : Between December 2007 and January 2010 , 46 patients with advanced HCC were treated with sorafenib until significant tumor progression or intolerable toxicity . We prospect ively collected clinical baseline data as well as data on the incidence and severity of toxic side effects of sorafenib to be correlated with progression-free survival and overall survival ( OS ) , respectively . Results : Only 26.1 % ( n = 12 ) of patients tolerated sorafenib without requiring dose reduction . The most frequent grade 3 toxicities were diarrhea ( 32.6 % ) , h and -foot skin reaction ( 13.0 % ) , fatigue ( 4.3 % ) , and nausea/vomiting ( 2.2 % ) . Eastern Cooperative Oncology Group performance status ( p = 0.034 ) and portal vein infiltration ( p = 0.021 ) significantly correlated with OS . Furthermore , we found a significant correlation between OS and appearance of grade 2 or 3 diarrhea with a median actuarial survival of 11.8 months ( 95 % CI 6.9–16.6 ) compared to 4.2 months in patients with grade 0 or 1 diarrhea ( 95 % CI 0.0–9.1 ; p = 0.009 ) . In contrast , appearance of h and -foot skin reaction did neither correlate with progression-free survival nor with OS . Conclusion : Appearance of grade 2 or 3 diarrhea indicates a better OS of HCC patients undergoing sorafenib treatment BACKGROUND & AIMS Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and , by measuring organ damage and tumor stage , can influence treatment . Moreover , elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma . We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment R and omized Protocol ( SHARP ) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , and bilirubin ; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment . METHODS Patients ( n=602 ) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase ( not significantly elevated , mildly elevated , or moderately elevated ) , alpha-fetoprotein ( normal or elevated ) , and bilirubin ( normal or elevated ) . Bilirubin was measured at baseline and on day 1 of each cycle . RESULTS Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin had shorter overall survival ( OS ) than those with normal baseline concentrations , irrespective of treatment group . No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin . Median changes from baseline in bilirubin concentration at the last cycle of treatment were + 0.17 and + 0.19 mg/dl in the sorafenib and placebo groups , respectively . CONCLUSIONS These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma , irrespective of baseline alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy Purpose : Hypertension is a mechanism-based toxicity of sorafenib and other cancer therapeutics that inhibit the vascular endothelial growth factor ( VEGF ) signaling pathway . This prospect i ve , single-center , cohort study characterized ambulatory blood pressure monitoring as an early pharmacodynamic biomarker of VEGF signaling pathway inhibition by sorafenib . Experimental Design : Fifty-four normotensive advanced cancer patients underwent 24-hour ambulatory blood pressure monitoring before and between days 6 and 10 of sorafenib therapy . After blood pressure changes were detected among the first cohort within 10 days , ambulatory blood pressure monitoring was done during the first 24 hours of treatment for the second cohort . Results : For the entire patient population , the blood pressure increase [ mean systolic , + 10.8 mm Hg ; 95 % confidence interval ( 95 % CI ) , 8.6 - 13.0 ; range , −5.2 to + 28.7 mm Hg ; mean diastolic , + 8.0 mm Hg ; 95 % CI , 6.3 - 9.7 ; range , −4.4 to + 27.1 mm Hg ] was detected between days 6 and 10 ( P < 0.0001 for both ) and plateaued thereafter . Variability in blood pressure change did not associate with : age , body size , sex , self-reported race , baseline blood pressure , or steady-state sorafenib plasma concentrations . In the second cohort , the blood pressure elevation was detected during the first 24 hours ( mean systolic , + 8.2 mm Hg ; 95 % CI , 5.0 - 11.3 ; mean diastolic , + 6.5 mm Hg ; 95 % CI , 4.7 - 8.3 ; P < 0.0001 for both ) . Conclusions : Ambulatory blood pressure monitoring detects the blood pressure response to VEGF signaling pathway inhibition by sorafenib during the first 24 hours of treatment . The magnitude of blood pressure elevation is highly variable and unpredictable but could be important in optimizing the therapeutic index of VEGF signaling pathway inhibitor therapy . ( Clin Cancer Res 2009;15(19):6250–7 PURPOSE Sorafenib has been found to have significant clinical activity against hepatocellular carcinoma ( HCC ) . H and -foot skin syndrome ( HFS ) has been described with the usage of sorafenib . It is a dose-limiting toxicity and may lead to compromised efficacy because of dose reduction . METHODS From 14 patients diagnosed with HCC 10 who developed HFS while on treatment with sorafenib were included in this study . Sorafenib was administered orally at a dose of 400 mg twice daily vitamin E usage can be effective in HFS due to sorafenib , therefore vitamin E 300 mg/day was started when HFS occurred . HFS was grade d according to the National Cancer Institute ( NCI ) criteria . RESULTS Grade 2 - 3 HFS was found in 10 of 14 patients . Vitamin E was started to all patients without using topical agents . Mean time to the appearance of HFS was 15 ± 3 days ( range 10 - 22 ) after starting sorafenib . Grade was 3 in 4 patients , 2 in 4 patients and 1 in 2 patients . Vitamin E administration had a marked effect after 10 - 12 days of its initiation . Skin lesions disappeared without any dose modification . CONCLUSION Sorafenib is the gold st and ard for HCC treatment . Dose modification due to HFS decreases the effectiveness of this agent . Adding vitamin E to sorafenib is effective in HFS without dose reduction or treatment interruption . This is the first clinical study to report resolution of HFS with vitamin E due to sorafenib therapy BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) . HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ; 451 patients received sorafenib and 452 received placebo . The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0.94 ; P=0.02 ) , although this benefit was not statistically significant according to the O'Brien-Fleming threshold . Partial responses were reported as the best response in 10 % of patients receiving sorafenib and in 2 % of those receiving placebo ( P<0.001 ) . Diarrhea , rash , fatigue , and h and -foot skin reactions were the most common adverse events associated with sorafenib . Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo . CONCLUSIONS As compared with placebo , treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed ; however , treatment is associated with increased toxic effects . ( Clinical Trials.gov number , NCT00073307 [ Clinical Trials.gov ] . ) BACKGROUND & AIMS Transarterial chemoembolization ( TACE ) is an important palliative treatment for unresectable hepatocellular carcinoma ( HCC ) , but TACE-induced ischemic injury can upregulate angiogenic factors and is associated with poor prognosis . The aim of this study was to evaluate the safety and efficacy of concurrent conventional TACE and sorafenib in patients with unresectable HCC . METHODS The primary objectives of this prospect i ve , single-arm , phase II study were to evaluate safety and time to progression ( TTP ) . Sorafenib was given 3 days after TACE and was administered for up to 24 weeks . Repeated TACE was performed on dem and . Tumor response was assessed every 8 weeks . RESULTS Fifty patients were treated and followed from July 2009 to May 2011 . All patients were in Barcelona Clinic Liver Cancer ( BCLC ) stage B ( 82 % ) or C ( 18 % ) . The median time of follow-up was 14.9 months and a median of 1 TACE session was given ( range , 1 - 4 ) . The median dose intensity of sorafenib was 68.7 % ( range , 37.3 - 100 ) of 800 mg daily . The most common reasons for dose reduction were h and -foot syndrome and thrombocytopenia . Thirty patients completed the study and 17 patients discontinued sorafenib due to disease progression . The overall median TTP was 7.1 months ( 95 % confidence interval ( CI ) , 4.8 - 7.5 months ) : 7.3 months in BCLC stage B ; 5.0 months in BCLC stage C. The 6-month progression-free survival rate was 52 % ( 95 % CI , 37.3 - 66.1 ) . CONCLUSIONS Concurrent treatment of unresectable HCC with conventional TACE and sorafenib demonstrates a manageable safety profile and a possibility of promising efficacy CONTEXT In a r and omized phase 3 trial , 400 mg of sorafenib twice daily prolonged overall survival of patients with advanced hepatocellular carcinoma ( HCC ) and Child-Pugh A disease . In a phase 1 study , sorafenib combined with doxorubicin , 60 mg/m(2 ) , was well tolerated by patients with refractory solid tumors . The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial . OBJECTIVE To evaluate the efficacy and safety of doxorubicin plus sorafenib compared with doxorubicin alone in patients with advanced HCC and Child-Pugh A disease . DESIGN , SETTING , AND PATIENTS In a double-blind phase 2 multinational study , conducted from April 2005 to October 2006 , 96 patients ( 76 % male ; median age , 65 years [ range , 38 - 82 years ] ) with advanced HCC , Eastern Cooperative Oncology Group performance status 0 to 2 , Child-Pugh A status , and no prior systemic therapy were r and omly assigned to receive 60 mg/m(2 ) of doxorubicin intravenously every 21 days plus either 400 mg of sorafenib or placebo orally twice a day . The date of the last patient 's follow-up was April 2008 . MAIN OUTCOME MEASURE Time to progression as determined by independent review . RESULTS Following complete accrual , an unplanned early analysis for efficacy was performed by the independent data monitoring committee , so the trial was halted . The 2 patients remaining in the placebo group at that time were offered sorafenib . Based on 51 progressions , 63 deaths , and 70 events for progression-free survival , median time to progression was 6.4 months in the sorafenib-doxorubicin group ( 95 % confidence interval [ CI ] , 4.8 - 9.2 ) , and 2.8 months ( 95 % CI , 1.6 - 5 ) in the doxorubicin-placebo monotherapy group ( P = .02 ) . Median overall survival was 13.7 months ( 95 % CI , 8.9 - -not reached ) and 6.5 months ( 95 % CI , 4.5 - 9.9 ; P = .006 ) , and progression-free survival was 6.0 months ( 95 % CI , 4.6 - 8.6 ) and 2.7 months ( 95 % CI , 1.4 - 2.8 ) in these groups , respectively ( P = .006 ) . Toxicity profiles were similar to those for the single agents . CONCLUSIONS Among patients with advanced HCC , treatment with sorafenib plus doxorubicin compared with doxorubicin monotherapy result ed in greater median time to progression , overall survival , and progression-free survival . The degree to which this improvement may represent synergism between sorafenib and doxorubicin remains to be defined . The combination of sorafenib and doxorubicin is not yet indicated for routine clinical use . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00108953 BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group ( hazard ratio in the sorafenib group , 0.69 ; 95 % confidence interval , 0.55 to 0.87 ; P<0.001 ) . There was no significant difference between the two groups in the median time to symptomatic progression ( 4.1 months vs. 4.9 months , respectively , P=0.77 ) . The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( P<0.001 ) . Seven patients in the sorafenib group ( 2 % ) and two patients in the placebo group ( 1 % ) had a partial response ; no patients had a complete response . Diarrhea , weight loss , h and -foot skin reaction , and hypophosphatemia were more frequent in the sorafenib group . CONCLUSIONS In patients with advanced hepatocellular carcinoma , median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo . ( Clinical Trials.gov number , NCT00105443 . BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma BACKGROUND & AIMS The Sorafenib Hepatocellular Carcinoma ( HCC ) Assessment R and omized Protocol ( SHARP ) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC . In this trial , 602 patients with well-preserved liver function ( > 95 % Child-Pugh A ) were r and omized to receive either sorafenib 400 mg or matching placebo orally b.i.d . on a continuous basis . Because HCC is a heterogeneous disease , baseline patient characteristics may affect individual responses to treatment . In a comprehensive series of exploratory subgroup analyses , data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib . METHODS Five subgroup domains were assessed : disease etiology , tumor burden , performance status , tumor stage , and prior therapy . Overall survival ( OS ) , time to progression ( TTP ) , disease control rate ( DCR ) , and safety were assessed for subgroups within each domain . RESULTS Subgroup analyses showed that sorafenib consistently improved median OS compared with placebo , as reflected by hazard ratios ( HRs ) of 0.50 - 0.85 , similar to the complete cohort ( HR=0.69 ) . Sorafenib also consistently improved median TTP ( HR , 0.40 - 0.64 ) , except in HBV-positive patients ( HR , 1.03 ) , and DCR . Results are limited by small patient numbers in some subsets . The most common grade 3/4 adverse events included diarrhea , h and -foot skin reaction , and fatigue ; the incidence of which did not differ appreciably among subgroups . CONCLUSIONS These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC , irrespective of disease etiology , baseline tumor burden , performance status , tumor stage , and prior therapy BACKGROUND The phase III Sorafenib Asia-Pacific ( AP ) trial-conducted in China , Taiwan and South Korea - confirmed that sorafenib improves overall survival ( OS ) and is safe for patients with advanced hepatocellular carcinoma ( HCC ) . We performed a series of exploratory subset analyses to determine whether baseline status affected response to sorafenib . METHODS In the Sorafenib AP trial , 226 patients with well-preserved liver function ( > 95 % Child-Pugh A ) were r and omised 2:1 to sorafenib 400 mg bid or matching placebo . Subanalyses were based on aetiology ( hepatitis B virus present/absent ) ; tumour burden ( macroscopic vascular invasion and /or extrahepatic spread present/absent ) ; presence or absence of either lung or lymph node metastasis at baseline , Eastern Cooperative Oncology Group performance status ( 0 , 1 - 2 ) ; serum concentrations of alanine aminotransferase/aspartate aminotransferase ( normal , mildly elevated , moderately elevated ) , alpha-fetoprotein ( normal/elevated ) and total bilirubin ( normal/elevated ) ; and whether or not there was a history of hepatectomy or transarterial chemoembolisation/embolisation . Subgroup assessment s included OS , time to progression ( TTP ) , disease control rate and safety . FINDINGS Sorafenib consistently improved both median OS and median TTP , compared with placebo ( range of hazard ratios ( HR ) , 0.32 - 0.87 and 0.31 - 0.75 , respectively ) . The most common grade 3/4 adverse events were h and -foot skin reaction , diarrhoea and fatigue , the incidence of which was similar between subgroups . INTERPRETATION The efficacy and safety profiles of sorafenib in the sub population s described were comparable with those in the overall study population . These exploratory analyses suggest that sorafenib is effective for patients from the AP region with advanced HCC , irrespective of baseline status BACKGROUND Recurrence of hepatocellular carcinoma ( HCC ) is a major problem after surgical or ablative treatments . The aim of this prospect i ve , single-center , placebo-controlled , r and omized , double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization ( TACE ) combined with sorafenib as a sequential treatment regimen in delaying time to progression ( TTP ) of intermediate-stage HCC in patients with chronic hepatitis C virus ( HCV ) infection . MATERIAL AND METHODS Between October , 2007 and January , 2011 , 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure . All had Child-Pugh class A disease . They were r and omized 1:1 to receive sorafenib at a dose of 400 mg twice daily or placebo . Endpoints were the TTP and the rates of adverse events and toxicity . RESULTS Sixty-two of 80 patients ( 77 % ) , 31 in the sorafenib group and 31 in the control group , completed the study . The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group ( hazard ratio , 2.5 ; 95 % confidence interval , 1.66 - 7.56 ; p < .001 ) . Metachronous , multicentric HCC progression occurred less frequently in sorafenib-treated patients ( p < .05 ) . Adverse reactions to sorafenib caused withdrawal from the study of 9 ( 22 % ) patients . CONCLUSION A conventional TACE procedure followed by sorafenib treatment result ed in a significantly longer TTP in patients with intermediate-stage HCV-related HCC , with no unexpected side effects |
2,150 | 30,270,924 | Statistically significant improvements in pain and disability were reported within but not between groups .
Conclusion Few trials have been conducted study ing thrust manipulation plus another conservative intervention for rotator cuff conditions rendering available evidence of thrust manipulation plus exercise insufficient to determine effects of this combined treatment | Objective To determine effects of thrust manipulation plus one conservative intervention for non-surgical shoulder pain and disability due to rotator cuff dysfunction . | & NA ; Myofascial trigger points ( TrPs ) have been clinical ly described as discrete areas of muscle tenderness presenting in taut b and s of skeletal muscle . Using well‐defined clinical criteria , prior investigations have demonstrated interrater reliability in the diagnosis of TrPs within a given muscle . No reports exist , however , with respect to the precision with which experienced clinicians can determine the anatomic locations of TrPs within a muscle . This paper details a study wherein four trained clinicians achieved statistically significant reliability ( see below ) in estimating the precise locations of latent TrPs in the trapezius muscle of volunteer subjects ( n=20 ) . To do so , the clinicians trained extensively together prior to the study . The precise anatomic location of each subject 's primary TrP was measured in a blinded fashion using a 3 dimensional ( 3‐D ) camera system . Use of this measurement system permitted the anatomic co‐ordinates of each TrP to be located without providing feedback to subsequent clinicians . The clinicians each used a pressure algometer along with patient feedback to document the sensitivity of each suspected TrP site , however unlike routine clinical practice , the algometry was performed with a double‐blinded approach hence the results were only examined post‐hoc . At the time of data collection ( algometry readings unknown ) , 16 of the 20 subjects were judged to present with a latent TrP. Subsequently , when subjected to a criterion pressure threshold value of < 3.0 kg.cm−2 , 12 of these TrPs were classified as being clinical ly sensitive . To assess the 3‐D measurement precision , and the reliability of the TrP estimates , statistical measures of the SEM and the Generalizability coefficient ( G‐coeff ) were determined for all suspected TrP sites in the superior‐inferior , medial‐lateral and anterior‐posterior directions . The best results were determined by pooling the measurements of all 4 clinicians , however , based upon exceeding a criterion reliability threshold of 80 % , the use of just two testers was found to produce reliable results . The two‐tester condition yielded a precision of 7.5 , 7.6 and 6.5 mm ( SEM ) with reliability ( G‐coeff ) of 0.92 , 0.86 and 0.83 , respectively . Given the double‐blinded methodology , the use of pressure algometry was also found to demonstrate internal validity . The algometer responses associated with TrP estimates varied inversely with respect to the clinical group 's reliability in identify the TrP locations . To summarize , for the trapezius muscle , this study demonstrates that two trained examiners can reliably localize latent TrPs with a precision that essentially approaches the physical dimensions of the clinician 's own fingertips . Finally , it should be recognized that the ability to precisely document TrP location appears critical to the success of future studies that may be design ed to investigate the etiology and pathogenesis of this commonly diagnosed clinical disorder OBJECTIVE To test the hypothesis that dry needle stimulation of a myofascial trigger point ( sensitive locus ) evokes segmental anti-nociceptive effects . DESIGN Double-blind r and omized controlled trial . SUBJECTS Forty subjects ( 21 males , 19 females ) . METHODS Test subjects received intramuscular dry needle puncture to a right supraspinatus trigger point ( C4,5 ) ; controls received sham intramuscular dry needle puncture . Pain pressure threshold ( PPT ) readings were recorded from right infraspinatus ( C5,6 ) and right gluteus medius ( L4,5S1 ) trigger points at 0 ( pre-needling baseline ) , 1 , 3 , 5 , 10 and 15 min post-needling and normalized to baseline values . The supraspinatus and infraspinatus trigger points are neurologically linked at C5 ; the supraspinatus and gluteus medius are segmentally unrelated . The difference between the infraspinatus and gluteus medius PPT values ( PPTseg ) represents a direct measure of the segmental anti-nociceptive effects acting at the infraspinatus trigger point . RESULTS Significant increases in PPTseg were observed in test subjects at 3 ( p = 0.002 ) and 5 ( p = 0.015 ) min post-needling , compared with controls . CONCLUSION One intervention of dry needle stimulation to a single trigger point ( sensitive locus ) evokes short-term segmental anti-nociceptive effects . These results suggest that trigger point ( sensitive locus ) stimulation may evoke anti-nociceptive effects by modulating segmental mechanisms , which may be an important consideration in the management of myofascial pain OBJECTIVES To determine the interexaminer reliability of palpation of three characteristics of trigger points ( taut b and , local twitch response , and referred pain ) in patients with subacute low back pain , to determine whether training in palpation would improve reliability , and whether there was a difference between the physiatric and chiropractic physicians . DESIGN Reliability study . SETTING Whittier Health Campus , Los Angeles College of Chiropractic . PARTICIPANTS Twenty-six nonsymptomatic individuals and 26 individuals with subacute low back pain . INTERVENTION Twenty muscles per individual were first palpated by an expert and then r and omly by four physician examiners . MAIN OUTCOME MEASURES Palpation findings . RESULTS Kappa scores for palpation of taut b and s , local twitch responses , and referred pain were .215 , .123 , and .342 , respectively , between the expert and the trained examiners , and .050 , .118 , and .326 , respectively , between the expert and the untrained examiners . Kappa scores for agreement for palpation of taut b and s , twitch responses , and referred pain were .108 , -.001 , and .435 , respectively , among the nonexpert , trained examiners , and -.019 , .022 , and .320 , respectively , among the nonexpert , untrained examiners . CONCLUSIONS Among nonexpert physicians , physiatric or chiropractic , trigger point palpation is not reliable for detecting taut b and and local twitch response , and only marginally reliable for referred pain after training The presence of a trigger point is essential to the myofascial pain syndrome . This study centres on identifying clearer criteria for the presence of trigger points in the quadratus lumborum and gluteus medius muscle by investigating the occurrence and inter-rater reliability of trigger point symptoms . Using the symptoms and signs as described by Simons ' 1990 definition and two other former sets of criteria , 61 non-specific low back pain patients and 63 controls were examined in general practice by 5 observers , working in pairs . From the two major criteria of Simons ' 1990 definition only ' localized tenderness ' has good discriminative ability and inter-rater reliability ( kappa > 0.5 ) . This study does not find proof for the clinical usefulness of ' referred pain ' , which has neither of these two abilities . The criteria ' jump sign ' and ' recognition ' , on the condition that localized tenderness is present , also have good discriminative ability and inter-rater reliability . Trigger points defined by the criteria found eligible in this study allow significant distinction between non-specific low back pain patients and controls . This is not the case with trigger points defined by Simons ' 1990 criteria . Concerning reliability there is also a significant difference between the two different criteria sets . This study suggests that the clinical usefulness of trigger points is increased when localized tenderness and the presence of either jump sign or patient 's recognition of his pain complaint are used as criteria for the presence of trigger points in the M. quadratus lumborum and the M. gluteus medius Objectives : To investigate the test-retest reliability of the following clinical diagnostic characteristics of myofascial trigger points : taut b and , spot tenderness , jump sign , pain recognition , referred pain and local twitch responses ( LTRs ) . Design : Test-retest reliability study . Setting : This study was undertaken in an outpatient physiotherapy department . Subjects : Fifty-eight patients ( 31 males and 27 females ) with rotator cuff tendonitis were recruited into this study . Intervention : Rotator cuff muscles were assessed by an expert for the presence or absence of the main clinical diagnostic characteristics of trigger point assessment . The process was then repeated three days later by the same expert . Main measures : Outcomes included the presence or absence of : a taut b and , spot tenderness , jump sign , pain recognition , referred pain and LTRs . Results : Kappa values between testing situations for the taut b and , spot tenderness , jump sign and pain recognition were 1 . Kappa scores for referred pain ranged between 0.79 and 0.88 and for the local twitch response between 0.75 and 1 depending on the muscles under investigation . Conclusions : The presence or absence of the taut b and , spot tenderness , jump sign and pain recognition was highly reliable between sessions . Referred pain and local twitch response reliability varied depending on the muscle being studied OBJECTIVE The purpose of this study was to investigate if spinal manipulative therapy ( SMT ) can evoke immediate regional antinociceptive effects in myofascial tissues by increasing pressure pain thresholds ( PPTs ) over myofascial trigger points in healthy young adults . METHODS A total of 36 participants ( 19 men , 17 women ; age , 28.0 [ 5.3 ] years ; body mass index , 26.5 [ 5.7 ] kg/m(2 ) ) with clinical ly identifiable myofascial trigger points in the infraspinatus and gluteus medius muscles were recruited from the University of Guelph , Ontario , Canada . Participants were r and omly allocated to 2 groups . Participants in the test group received chiropractic SMT targeted to the C5-C6 spinal segment . Participants in the control group received sham SMT . The PPT was recorded from the right infraspinatus and gluteus medius muscles at baseline ( preintervention ) and 1 , 5 , 10 , and 15 minutes postintervention . RESULTS Three participants were disqualified , result ing in a total of 33 participants analyzed . Significant increases in the PPT ( decreased pain sensitivity ) were observed in the test infraspinatus group when compared with test gluteus medius , control infraspinatus , and control gluteus medius groups ( P < .05 ) . No significant differences in PPT were observed at any time point when comparing test gluteus medius , control infraspinatus , and control gluteus medius groups ( P > .05 ) . CONCLUSIONS This study showed that SMT evokes short-term regional increases in PPT within myofascial tissues in healthy young adults Abstract The myofascial trigger point ( MTrP ) is the hallmark physical finding of the myofascial pain syndrome ( MPS ) . The MTrP itself is characterized by distinctive physical features that include a tender point in a taut b and of muscle , a local twitch response ( LTR ) to mechanical stimulation , a pain referral pattern characteristic of trigger points of specific areas in each muscle , and the reproduction of the patient 's usual pain . No prior study has demonstrated that these physical features are reproducible among different examiners , thereby establishing the reliability of the physical examination in the diagnosis of the MPS . This paper reports an initial attempt to establish the interrater reliability of the trigger point examination that failed , and a second study by the same examiners that included a training period and that successfully established interrater reliability in the diagnosis of the MTrP. The study also showed that the interrater reliability of different features varies , the LTR being the most difficult , and that the interrater reliability of the identification of MTrP features among different muscles also varies Objective . Increasing research interest and emerging new therapies for treatment of fibromyalgia ( FM ) have led to a need to develop a consensus on a core set of outcome measures that should be assessed and reported in all clinical trials , to facilitate interpretation of the data and underst and ing of the disease . This aligns with the key objective of the Outcome Measures in Rheumatology ( OMERACT ) initiative to improve outcome measurement through a data driven , interactive consensus process . Methods . Through patient focus groups and Delphi processes , working groups at previous OMERACT meetings identified potential domains to be included in the core data set . A systematic review has shown that instruments measuring these domains are available and are at least moderately sensitive to change . Most instruments have been vali date d in multiple language s. This pooled analysis study aims to develop the core data set by analyzing data from 10 r and omized controlled trials ( RCT ) in FM . Results . Results from this study provide support for the inclusion of the following in the core data set : pain , tenderness , fatigue , sleep , patient global assessment , and multidimensional function/health related quality of life . Construct validity was demonstrated with outcome instruments showing convergent and divergent validity . Content and criterion validity were confirmed by multivariate analysis showing R square values between 0.4 and 0.6 . Low R square value is associated with studies in which one or more domains were not assessed . Conclusion . The core data set was supported by high consensus among attendees at OMERACT 9 . Establishing an international st and ard for RCT in FM should facilitate future metaanalyses and indirect comparisons OBJECTIVE To examine prospect ively the accuracy of an initial diagnosis for fibromyalgia ( FM ) . METHODS All patients newly referred for rheumatology consultation in a 6-month period were evaluated prospect ively for either a preceding , current or subsequent diagnosis of FM . Clinical characteristics , previous and subsequent management and health care utilization were assessed . The final diagnosis at 6 months was verified and accuracy regarding the diagnosis of FM was assessed . RESULTS Seventy six ( 12 % ) of all new patients were either referred with a question of FM or finally diagnosed with FM . At the final evaluation the accuracy of the diagnosis regarding FM by either the referring physician or by the rheumatologist at the time of the initial visit was correct in 34 % of patients . The FM group in comparison with those with some other rheumatological diagnosis had more tender points ( 12.5 vs 4 ) and were more fatigued . In contrast , prolonged early morning stiffness and limitation of lumbar spinal mobility in more than one plane was more common in the non-FM group . CONCLUSION There is a disturbing inaccuracy , mostly observed to be overdiagnosis , in the diagnosis of FM by referring physicians . This finding may help explain the current high reported rates of FM and caution physicians to consider other diagnostic possibilities when addressing diffuse musculoskeletal pain |
2,151 | 30,411,242 | Results Although conflicting literature exists , the majority of the current evidence points toward CYP2D6 genetic variation affecting survival outcomes after tamoxifen treatment .
Conclusions and recommendations Critical appraisal of the literature provided evidence for the value of comprehensive CYP2D6 genotyping panels in guiding treatment decisions for non-metastatic ER-positive breast cancer patients . | Purpose Tamoxifen is one of the principal treatments for estrogen receptor (ER)-positive breast cancer .
Unfortunately , between 30 and 50 % of patients receiving this hormonal therapy relapse .
Since CYP2D6 genetic variants have been reported to play an important role in survival outcomes after treatment with tamoxifen , this study sought to summarize and critically appraise the available scientific evidence on this topic . | BACKGROUND Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and , to our knowledge , no trial has directly compared the three aromatase inhibitors anastrozole , exemestane , and letrozole . We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer . METHODS FATA-GIM3 is a multicentre , open-label , r and omised , phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer . Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery , any pathological tumour size , and axillary nodal status . Key exclusion criteria were hormone replacement therapy , recurrent or metastatic disease , previous treatment with tamoxifen , and another malignancy in the previous 10 years . Patients were r and omly assigned in an equal ratio to one of six treatment groups : oral anastrozole ( 1 mg per day ) , exemestane ( 25 mg per day ) , or letrozole ( 2·5 mg per day ) tablets upfront for 5 years ( upfront strategy ) or oral tamoxifen ( 20 mg per day ) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years ( switch strategy ) . R and omisation was done by a computerised minimisation procedure stratified for oestrogen receptor , progesterone receptor , and HER2 status ; previous chemotherapy ; and pathological nodal status . Neither the patients nor the physicians were masked to treatment allocation . The primary endpoint was disease-free survival . The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2 % difference in disease-free survival at 5 years . Primary efficacy analyses were done by intention to treat ; safety analyses included all patients for whom at least one safety case report form had been completed . Follow-up is ongoing . This trial is registered with the European Clinical Trials Data base , number 2006 - 004018 - 42 , and Clinical Trials.gov , number NCT00541086 . FINDINGS Between March 9 , 2007 , and July 31 , 2012 , 3697 patients were enrolled into the study . After a median follow-up of 60 months ( IQR 46 - 72 ) , 401 disease-free survival events were reported , including 211 ( 11 % ) of 1850 patients allocated to the switch strategy and 190 ( 10 % ) of 1847 patients allocated to upfront treatment . 5-year disease-free survival was 88·5 % ( 95 % CI 86·7 - 90·0 ) with the switch strategy and 89·8 % ( 88·2 - 91·2 ) with upfront treatment ( hazard ratio 0·89 , 95 % CI 0·73 - 1·08 ; p=0·23 ) . 5-year disease-free survival was 90·0 % ( 95 % CI 87·9 - 91·7 ) with anastrozole ( 124 events ) , 88·0 % ( 85·8 - 89·9 ) with exemestane ( 148 events ) , and 89·4 % ( 87·3 to 91·1 ) with letrozole ( 129 events ; p=0·24 ) . No unexpected serious adverse reactions or treatment-related deaths occurred . Musculoskeletal side-effects were the most frequent grade 3 - 4 events , reported in 130 ( 7 % ) of 1761 patients who received the switch strategy and 128 ( 7 % ) of 1766 patients who received upfront treatment . Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule ( 924 [ 52 % ] of 1766 patients vs 745 [ 42 % ] of 1761 patients ) . All other grade 3 - 4 adverse events occurred in less than 2 % of patients in either group . INTERPRETATION 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors . None of the three aromatase inhibitors was superior to the others in terms of efficacy . Therefore , patient preference , tolerability , and financial constraints should be considered when deciding the optimal treatment approach in this setting . FUNDING Italian Drug Agency Background : The effect of tamoxifen dose elevation on endoxifen serum concentration was investigated in patients with reduced CYP2D6 activity result ing from genetic variation and /or CYP2D6 inhibitor use . Additionally , baseline differences in endoxifen concentrations between the different CYP2D6 phenotypes were studied . Methods : Patients , treated with tamoxifen 20 mg once daily ( QD ) for at least 4 weeks , were classified as phenotypic extensive ( EM ) , intermediate ( IM ) , or poor ( PM ) metabolizer based on their genotype and comedication . In patients with an IM or PM phenotype , the tamoxifen dose was increased to 40 mg QD for 4 weeks . Tamoxifen , 4-OH-tamoxifen , N-desmethyltamoxifen , and endoxifen serum concentrations were measured at baseline and 4 weeks after the dose increment . Side effects of tamoxifen were assessed using the vali date d Functional Assessment of Cancer Therapy – Endocrine Symptom subscale ( FACT-ESS-19 ) . Results : The median baseline endoxifen concentration differed between EMs ( 11.4 mcg/L : n = 19 ) , IMs ( 8.3 mcg/L : n = 16 ) , and PMs ( 4.0 mcg/L : n = 7 ) , P = 0.040 . Tamoxifen dose elevation significantly increased the median endoxifen concentrations in 12 IMs from 9.5 to 17.4 mcg/L ( P < 0.001 ) and in 4 PMs from 3.8 to 7.8 mcg/L ( P = 0.001 ) , without influencing median FACT-ESS-19 scores . Conclusions : Raising the tamoxifen dose to 40 mg QD significantly increased endoxifen concentrations in IMs and PMs without increasing side effects . The tamoxifen dose increment in PMs was insufficient to reach endoxifen concentrations equal to those observed in EMs . Future studies will clarify the direct effect of endoxifen exposure on tamoxifen efficacy and may reveal a threshold endoxifen concentration that is critical for its efficacy PURPOSE Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women . Any long-term effects on estrogen-sensitive tissues such as bone may have important therapeutic implication s. METHODS We measured bone mineral density ( BMD ) in the lumbar spine and hip using dual-energy x-ray absorptiometry ( DXA ) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial . RESULTS BMD data are now available from 179 women for this analysis . In premenopausal women , BMD decreased progressively in the lumbar spine ( P < .001 ) and in the hip ( P < .05 ) for women on tamoxifen , but not those on placebo . The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44 % ( 1.88 % calculated on an intent-to-treat basis ) compared with a small gain of 0.24 % per annum for women on placebo ( P < .001 ) . Tamoxifen had the opposite effect in postmenopausal women . The mean annual increase in BMD for women on tamoxifen was 1.17 % in the spine ( P < .005 ) and 1.71 % in the hip ( P < .001 ) compared with a noninsignificant loss for women on placebo . CONCLUSION These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women , whereas it prevents bone loss in postmenopausal women . These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer BACKGROUND The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ . This report assesses the effect of these drugs on quality of life and symptoms . METHODS The study was done at 333 hospitals in North America . Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole breast irradiation were r and omly assigned to receive either tamoxifen ( 20 mg/day ) or anastrazole ( 1 mg/day ) for 5 years , stratified by age ( < 60 years vs ≥60 years ) . Patients and investigators were masked to treatment allocation . Patients completed question naires at baseline and every 6 months thereafter for 6 years . The primary outcomes were SF-12 physical and mental health component scale scores , and vasomotor symptoms ( as per the BCPT symptom scale ) . Secondary outcomes were vaginal symptoms and sexual functioning . Exploratory outcomes were musculoskeletal pain , bladder symptoms , gynaecological symptoms , cognitive symptoms , weight problems , vitality , and depression . We did the analyses by intention to treat , including patients who completed question naires at baseline and at least once during follow-up . This study is registered with Clinical Trials.gov , NCT00053898 . FINDINGS Between Jan 6 , 2003 , and June 15 , 2006 , 3104 patients were enrolled in the study , of whom 1193 were included in the quality -of-life sub study : 601 assigned to tamoxifen and 592 assigned to anastrozole . We detected no significant difference between treatment groups for : physical health scores ( mean severity score 46·72 for tamoxifen vs 45·85 for anastrozole ; p=0·20 ) , mental health scores ( 52·38 vs 51·48 ; p=0·38 ) , energy and fatigue ( 58·34 vs 57·54 ; p=0·86 ) , or symptoms of depression ( 6·19 vs 6·39 ; p=0·46 ) over 5 years . Vasomotor symptoms ( 1·33 vs 1·17 ; p=0·011 ) , difficulty with bladder control ( 0·96 vs 0·80 ; p=0·0002 ) , and gynaecological symptoms ( 0·29 vs 0·18 ; p<0·0001 ) were significantly more severe in the tamoxifen group than in the anastrozole group . Musculoskeletal pain ( 1·50 vs 1·72 ; p=0·0006 ) and vaginal symptoms ( 0·76 vs 0·86 ; p=0·035 ) were significantly worse in the anastrozole group than in the tamoxifen group . Sexual functioning did not differ significantly between the two treatments ( 43·65 vs 45·29 ; p=0·56 ) . Younger age was significantly associated with more severe vasomotor symptoms ( mean severity score 1·45 for age < 60 years vs 0·65 for age ≥60 years ; p=0·0006 ) , vaginal symptoms ( 0·98 vs 0·65 ; p<0·0001 ) , weight problems ( 1·32 vs 1·02 ; p<0·0001 ) , and gynaecological symptoms ( 0·26 vs 0·22 ; p=0·014 ) . INTERPRETATION Given the similar efficacy of tamoxifen and anastrozole for women older than age 60 years , decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug . For women younger than 60 years old , treatment decisions might be driven by efficacy ( favouring anastrozole ) ; however , if the side-effects of anastrozole are intolerable , then switching to tamoxifen is a good alternative . FUNDING US National Cancer Institute , AstraZeneca Pharmaceuticals Summary Because treatment for breast cancer may adversely affect skeletal metabolism , we investigated vertebral fracture risk in women with non-metastatic breast cancer . The prevalence of vertebral fracture was similar in women at the time of first diagnosis to that in an age-matched sample of the general population . The incidence of vertebral fracture , however , was nearly five times greater than normal in women from the time of first diagnosis [ odds ratio ( OR ) , 4.7 ; 95 % confidence interval ( 95 % CI ) , 2.3–9.9 ] , and 20-fold higher in women with soft-tissue metastases without evidence of skeletal metastases ( OR , 22.7 ; 95 % CI , 9.1–57.1 ) . We conclude that vertebral fracture risk is markedly increased in women with breast cancer BACKGROUND Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer . Cytochrome P450 2D6 ( CYP2D6 ) enzyme metabolizes tamoxifen to clinical ly active metabolites , and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy . In this study , we investigated the clinical relevance of CYP2D6 polymorphisms . METHODS We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor-positive breast cancer who enrolled in the r and omized , phase III double-blind Breast International Group ( BIG ) 1 - 98 trial between March 1998 and May 2003 and received tamoxifen and /or letrozole treatment . Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction-based methods . Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor , intermediate , and extensive metabolizers ( PM , IM , and EM , respectively ; n = 4393 patients ) . Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval ( referred to as recurrence ) and treatment-induced hot flushes according to r and omized endocrine treatment and previous chemotherapy were assessed . Cox proportional hazards models were used to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy ( P = .35 ) . PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype ( PM or IM vs EM , HR of recurrence = 0.86 , 95 % CI = 0.60 to 1.24 ) . CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes ( P = .020 ) . Both PM and IM phenotypes had an increased risk of tamoxifen-induced hot flushes compared with EM phenotype ( PM vs EM , HR of hot flushes = 1.24 , 95 % CI = 0.96 to 1.59 ; IM vs EM , HR of hot flushes = 1.23 , 95 % CI = 1.05 to 1.43 ) . CONCLUSIONS CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes , contrary to the hypothesis . The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment . CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations , without increasing toxicity . From a prospect i ve study population of early breast cancer patients using tamoxifen ( CYPTAM : NTR1509 ) , 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months . The escalated dose was calculated by multiplying the individual ’s endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg ( 120 mg maximum ) . Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months , just before patients returned to the st and ard dose of 20 mg . Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations ( p < 0.001 ; p = 0.002 , respectively ) without increasing side effects . In intermediate metabolizers , dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers . In poor metabolizers , the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers . In all patients , the endoxifen threshold of 5.97 ng/ml ( = 16.0 nM ) reported by Madlensky et al. was reached following dose escalation . CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects . Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored Inferring CYP2D6 phenotype from genotype is increasingly challenging , considering the growing number of alleles and their range of activity . This complexity poses a challenge in translational research where genotyping is being considered as a tool to personalize drug therapy . To simplify genotype interpretation and improve phenotype prediction , we evaluated the utility of an “ activity score ” ( AS ) system . Over 25 CYP2D6 allelic variants were genotyped in 672 subjects of primarily Caucasian and African‐American heritage . The ability of genotype and AS to accurately predict phenotype using the CYP2D6 probe substrate dextromethorphan was evaluated using linear regression and clustering methods . Phenotype prediction , given as a probability for each AS group , was most accurate if ethnicity was considered ; among subjects with genotypes containing a CYP2D6 * 2 allele , CYP2D6 activity was significantly slower in African Americans compared to Caucasians . The AS tool warrants further prospect i ve evaluation for CYP2D6 substrates and in additional ethnic population BACKGROUND AND METHODS Tamoxifen , a synthetic antiestrogen , increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer . Because it is given for long periods , it is important to know whether tamoxifen affects the skeleton , particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis . Using photon absorptiometry , we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node-negative breast cancer , in a two-year r and omized , double-blind , placebo-controlled trial . RESULTS In the women given tamoxifen , the mean bone mineral density of the lumbar spine increased by 0.61 percent per year , whereas in those given placebo it decreased by 1.00 percent per year ( P less than 0.001 ) . Radial bone mineral density decreased to the same extent in both groups . In a subgroup r and omly selected from each group , serum osteocalcin and alkaline phosphatase concentrations decreased significantly in women given tamoxifen ( P less than 0.001 for each variable ) , whereas serum parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not change significantly in either group . CONCLUSIONS In postmenopausal women , treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine . Whether this favorable effect on bone mineral density is accompanied by a decrease in the risk of fractures remains to be determined Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer , known to undergo CYP2D6-mediated bioactivation to endoxifen . However , little is known regarding additional genetic and non-genetic determinants of optimal endoxifen plasma concentration . Therefore , 196 breast cancer patients on tamoxifen were enrolled in this prospect i ve study over a 24-month period . Blood sample s were collected for pharmacogenetic and drug-level analysis of tamoxifen and metabolites . Regression analysis indicated that besides CYP2D6 , the recently described CYP3A4 * 22 genotype , seasonal variation , and concomitant use of CYP2D6-inhibiting antidepressants were significant predictors of endoxifen concentration . Of note , genetic variation explained 33 % of the variability while non-genetic variables accounted for 13 % . Given the proposed notion of a sub-therapeutic endoxifen concentration for predicting breast cancer recurrence , we set the therapeutic threshold at 18 nM , the 20th percentile for endoxifen level among enrolled patients in this cohort . Nearly 70 % of CYP2D6 poor metabolizers as well as extensive metabolizers on potent CYP2D6-inhibiting antidepressants exhibited endoxifen levels below 18 nM , while carriers of CYP3A4 * 22 were twofold less likely to be in sub-therapeutic range . Unexpectedly , endoxifen levels were 20 % lower during winter months than mean levels across seasons , which was also associated with lower vitamin D levels . CYP3A4 * 22 genotype along with sunshine exposure and vitamin D status may be unappreciated contributors of tamoxifen efficacy . The identified covariates along with demographic variables were integrated to create an endoxifen concentration prediction algorithm to pre-emptively evaluate the likelihood of individual patients falling below the optimal endoxifen concentration Purpose : CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen , “ endoxifen . ” There are still controversial reports question ing the association between CYP2D6 genotype and tamoxifen efficacy . Hence , we performed a prospect i ve multicenter study to evaluate the clinical effect of CYP2D6 genotype on tamoxifen therapy . Experimental Design : We enrolled 279 patients with hormone receptor – positive and human epidermal growth factor receptor 2-negative , invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days . Ki-67 response in breast cancer tissues after tamoxifen therapy was used as a surrogate marker for response to tamoxifen . We prospect ively investigated the effects of allelic variants of CYP2D6 on Ki-67 response , pathological response , and hot flushes . Results : Ki-67 labeling index in breast cancer tissues significantly decreased after preoperative tamoxifen monotherapy ( P = 0.0000000000000013 ) . Moreover , proportion and Allred scores of estrogen receptor – positive cells in breast cancer tissues were significantly associated with Ki-67 response ( P = 0.0076 and 0.0023 , respectively ) . Although CYP2D6 variants were not associated with pathologic response nor hot flushes , they showed significant association with Ki-67 response after preoperative tamoxifen therapy ( P = 0.018 ; between two groups , one with at least one wild-type allele and the other without a wild-type allele ) . Conclusions : This is the first prospect i ve study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy . Our results suggest that genetic variation in CYP2D6 is a key predictor for the response to tamoxifen in patients with breast cancer . Clin Cancer Res ; 23(8 ) ; 2019–26 . © 2016 AACR BACKGROUND Polymorphic CYP2D6 is primarily responsible for metabolic activation of tamoxifen to endoxifen . We previously reported that by increasing the daily tamoxifen dose to 40 mg/day in CYP2D6 intermediate metabolizer ( IM ) , but not poor metabolizer ( PM ) , patients achieve endoxifen concentrations similar to those of extensive metabolizer patients on 20 mg/day . We exp and ed enrollment to assess the safety of CYP2D6 genotype-guided dose escalation and investigate concentration differences between races . METHODS PM and IM breast cancer patients currently receiving tamoxifen at 20 mg/day were enrolled for genotype-guided escalation to 40 mg/day . Endoxifen was measured at baseline and after 4 months . Quality -of-life data were collected using the Functional Assessment of Cancer Therapy-Breast ( FACT-B ) and Breast Cancer Prevention Trial Menopausal Symptom Scale at baseline and after 4 months . RESULTS In 353 newly enrolled patients , genotype-guided dose escalation eliminated baseline concentration differences in IM ( p = .08 ) , but not PM ( p = .009 ) , patients . Endoxifen concentrations were similar in black and white patients overall ( p = .63 ) and within CYP2D6 phenotype groups ( p > .05 ) . In the quality -of-life analysis of 480 patients , dose escalation did not meaningfully diminish quality of life ; in fact , improvements were seen in several measures including the FACT Breast Cancer subscale ( p = .004 ) and limitations in range of motion ( p < .0001 ) in IM patients . CONCLUSION Differences in endoxifen concentration during treatment can be eliminated by doubling the tamoxifen dose in IM patients , without an appreciable effect on quality of life . Validation of the association between endoxifen concentration and efficacy or prospect i ve demonstration of improved efficacy is necessary to warrant clinical uptake of this personalized treatment strategy . IMPLICATION S FOR PRACTICE This secondary analysis of a prospect i ve CYP2D6 genotype-guided tamoxifen dose escalation study confirms that escalation to 40 mg/day in patients with low-activity CYP2D6 phenotypes ( poor or intermediate metabolizers ) increases endoxifen concentrations without any obvious increases in treatment-related toxicity . It remains unknown whether endoxifen concentration is a useful predictor of tamoxifen efficacy , and thus , there is no current role in clinical practice for CYP2D6 genotype-guided tamoxifen dose adjustment . If future studies confirm the importance of endoxifen concentrations for tamoxifen efficacy and report a target concentration , this study provides guidance for a dose-adjustment approach that could maximize efficacy while maintaining patient quality of life Part I of this article discussed the potential functional importance of genetic mutations and alleles of the human cytochrome P450 2D6 ( CYP2D6 ) gene . The impact of CYP2D6 polymorphisms on the clearance of and response to a series of cardiovascular drugs was addressed . Since CYP2D6 plays a major role in the metabolism of a large number of other drugs , Part II of the article highlights the impact of CYP2D6 polymorphisms on the response to other groups of clinical ly used drugs . Although clinical studies have observed a gene-dose effect for some tricyclic antidepressants , it is difficult to establish clear relationships of their pharmacokinetics and pharmacodynamic parameters to genetic variations of CYP2D6 ; therefore , dosage adjustment based on the CYP2D6 phenotype can not be recommended at present . There is initial evidence for a gene-dose effect on commonly used selective serotonin reuptake inhibitors ( SSRIs ) , but data on the effect of the CYP2D6 genotype/phenotype on the response to SSRIs and their adverse effects are scanty . Therefore , recommendations for dose adjustment of prescribed SSRIs based on the CYP2D6 genotype/phenotype may be premature . A number of clinical studies have indicated that there are significant relationships between the CYP2D6 genotype and steady-state concentrations of perphenazine , zuclopenthixol , risperidone and haloperidol . However , findings on the relationships between the CYP2D6 genotype and parkinsonism or tardive dyskinesia treatment with traditional antipsychotics are conflicting , probably because of small sample size , inclusion of antipsychotics with variable CYP2D6 metabolism , and co-medication . CYP2D6 phenotyping and genotyping appear to be useful in predicting steady-state concentrations of some classical antipsychotic drugs , but their usefulness in predicting clinical effects must be explored . Therapeutic drug monitoring has been strongly recommended for many antipsychotics , including haloperidol , chlorpromazine , fluphenazine , perphenazine , risperidone and thioridazine , which are all metabolized by CYP2D6 . It is possible to merge therapeutic drug monitoring and pharmacogenetic testing for CYP2D6 into clinical practice .There is a clear gene-dose effect on the formation of O-demethylated metabolites from multiple opioids , but the clinical significance of this may be minimal , as the analgesic effect is not altered in poor metabolizers ( PMs ) . Genetically caused inactivity of CYP2D6 renders codeine ineffective owing to lack of morphine formation , decreases the efficacy of tramadol owing to reduced formation of the active O-desmethyltramadol and reduces the clearance of methadone . Genetically precipitated drug interactions might render a st and ard opioid dose toxic . Because of the important role of CYP2D6 in tamoxifen metabolism and activation , PMs are likely to exhibit therapeutic failure , and ultrarapid metabolizers ( UMs ) are likely to experience adverse effects and toxicities . There is a clear gene-concentration effect for the formation of endoxifen and 4-OH-tamoxifen . Tamoxifen-treated cancer patients carrying CYP2D6 * 4 , * 5 , * 10 , or * 41 associated with significantly decreased formation of antiestrogenic metabolites had significantly more recurrences of breast cancer and shorter relapse-free periods . Many studies have identified the genetic CYP2D6 status as an independent predictor of the outcome of tamoxifen treatment in women with breast cancer , but others have not observed this relationship . Thus , more favourable tamoxifen treatment seems to be feasible through a priori genetic assessment of CYP2D6 , and proper dose adjustment may be needed when the CYP2D6 genotype is determined in a patient . Dolasetron , ondansetron and tropisetron , all in part metabolized by CYP2D6 , are less effective in UMs than in other patients . Overall , there is a strong gene-concentration relationship only for tropisetron . CYP2D6 genotype screening prior to antiemetic treatment may allow for modification of antiemetic dosing . An alternative is to use a serotonin agent that is metabolized independently of CYP2D6 , such as granisetron , which would obviate the need for genotyping and may lead to an improved drug response . To date , the functional impact of most CYP2D6 alleles has not been systematic ally assessed for most clinical ly important drugs that are mainly metabolized by CYP2D6 , though some initial evidence has been identified for a very limited number of drugs . The majority of reported in vivo pharmacogenetic data on CYP2D6 are from single-dose and steady-state pharmacokinetic studies of a small number of drugs . Pharmacodynamic data on CYP2D6 polymorphisms are scanty for most drug studies . Given that genotype testing for CYP2D6 is not routinely performed in clinical practice and there is uncertainty regarding genotype-phenotype , gene-concentration and gene-dose relationships , further prospect i ve studies on the clinical impact of CYP2D6-dependent metabolism of drugs are warranted in large cohorts |
2,152 | 31,116,259 | RESULTS The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex , anterior cingulate , posterior parietal regions , and amygdala in both pediatric and adult GAD patients , mostly in the right hemisphere . | OBJECTIVES Brain imaging studies carried out in patients suffering from generalized anxiety disorder ( GAD ) have contributed to better characterize the pathophysiological mechanisms underlying this disorder .
The present study review s the available functional and structural brain imaging evidence on GAD , and suggests further strategies for investigations in this field . | The ventral tegmental area ( VTA ) has been primarily implicated in reward-motivated behavior . Recently , aberrant dopaminergic VTA signaling has also been implicated in anxiety-like behaviors in animal models . These findings , however , have yet to be extended to anxiety in humans . Here we hypothesized that clinical anxiety is linked to dysfunction of the mesocorticolimbic circuit during threat processing in humans ; specifically , excessive or dysregulated activity of the mesocorticolimbic aversion circuit may be etiologically related to errors in distinguishing cues of threat versus safety , also known as “ overgeneralization of fear . ” To test this , we recruited 32 females with generalized anxiety disorder and 25 age-matched healthy control females . We measured brain activity using fMRI while participants underwent a fear generalization task consisting of pseudo-r and omly presented rectangles with systematic ally varying widths . A mid-sized rectangle served as a conditioned stimulus ( CS ; 50 % electric shock probability ) and rectangles with widths of CS ±20 % , ±40 % , and ±60 % served as generalization stimuli ( GS ; never paired with electric shock ) . Healthy controls showed VTA reactivity proportional to the cue 's perceptual similarity to CS ( threat ) . In contrast , patients with generalized anxiety disorder showed heightened and less discriminating VTA reactivity to GS , a feature that was positively correlated with trait anxiety , as well as increased mesocortical and decreased mesohippocampal coupling . Our results suggest that the human VTA and the mesocorticolimbic system play a crucial role in threat processing , and that abnormalities in this system are implicated in maladaptive threat processing in clinical anxiety The role of worry in generalized anxiety disorder ( GAD ) has been posited to serve as an avoidance of emotional experience , and emotion regulation deficits in GAD have been found in several previous studies . It remains unclear whether those with GAD experience more dysregulated emotions during periods of euthymia and positive affect or whether these deficits occur only during periods of worry . Individuals with GAD ( with and without co-occurring dysphoria ) and non-anxious controls were r and omly assigned to receive a worry , neutral , or relaxation induction . Following the induction , all participants viewed a film clip documented to elicit sadness . Intensity of emotions and emotion regulation were examined following the induction period and film clip . The results revealed that , regardless of co-occurring dysphoria , individuals with GAD in the worry condition experienced more intense depressed affect than GAD participants in the other conditions and controls participants . In contrast , presence of worry appeared to have less impact on indices of emotion dysregulation , which were greater in participants with GAD compared to controls , but largely insensitive to context ual effects of worry or of relaxation . Following film viewing , both GAD participants with and without dysphoria displayed poorer underst and ing , acceptance , and management of emotions than did controls . However , acceptance and management deficits were most pronounced in individuals with both GAD and co-occurring dysphoria . Implication s for the role of emotions in conceptualization and treatment of GAD are discussed Theory of Mind ( ToM ) , the ability to attribute mental states to others , and empathy , the ability to infer emotional experiences , are important processes in social cognition . Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex , superior temporal sulcus and temporal pole in ToM processing . Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions . In this fMRI study , we used a cartoon task derived from Sarfati et al. ( 1997 ) [ Sarfati , Y. , Hardy-Bayle , M.C. , Besche , C. , Widlocher , D. 1997 . Attribution of intentions to others in people with schizophrenia : a non-verbal exploration with comic strips . Schizophrenia Research 25 , 199 - 209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes . Results of 13 right-h and ed , healthy , male volunteers were included . Functional images were acquired using a 1.5 T Phillips Gyroscan . Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks . Common areas of activation included the medial prefrontal cortex , temporoparietal junction and temporal poles . Compared to the empathy condition , ToM stimuli revealed increased activations in lateral orbitofrontal cortex , middle frontal gyrus , cuneus and superior temporal gyrus . Empathy , on the other h and , was associated with enhanced activations of paracingulate , anterior and posterior cingulate and amygdala . We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others . However , empathic responding requires the additional recruitment of networks involved in emotional processing . These results have implication s for our underst and ing of disorders characterized by impairments of social cognition , such as autism and psychopathy As a central fear processor of the brain , the amygdala initiates a cascade of critical physiological and behavioral responses . Neuroimaging studies have shown that the human amygdala responds not only to fearful and angry facial expressions but also to fearful and threatening scenes such as attacks , explosions , and mutilations . Given the relative importance of facial expressions in adaptive social behavior , we hypothesized that the human amygdala would exhibit a stronger response to angry and fearful facial expressions in comparison to other fearful and threatening stimuli . Twelve subjects completed two tasks while undergoing fMRI : matching angry or fearful facial expressions , and matching scenes depicting fearful or threatening situations derived from the International Affective Picture System ( IAPS ) . While there was an amygdala response to both facial expressions and IAPS stimuli , direct comparison revealed that the amygdala response to facial expressions was significantly greater than that to IAPS stimuli . Autonomic reactivity , measured by skin conductance responses , was also greater to facial expressions . These results suggest that the human amygdala shows a stronger response to affective facial expressions than to scenes , a bias that should be considered in the design of experimental paradigms interested in probing amygdala function Mindfulness training aims to impact emotion regulation . Generalized anxiety disorder ( GAD ) symptoms can be successfully addressed through mindfulness-based interventions . This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training . Furthermore , we compared brain activation between GAD patients and healthy participants at baseline . 26 patients with a current DSM-IV GAD diagnosis were r and omized to an 8-week Mindfulness Based Stress Reduction ( MBSR , N = 15 ) or a stress management education ( SME , N = 11 ) active control program . 26 healthy participants were included for baseline comparisons . BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions . At baseline , GAD patients showed higher amygdala activation than healthy participants in response to neutral , but not angry faces , suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients . In patients , amygdala activation in response to neutral faces decreased following both interventions . BOLD response in ventrolateral prefrontal regions ( VLPFC ) showed greater increase in MBSR than SME participants . Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR , but not SME group . Both , change in VLPFC activation and amygdala – prefrontal connectivity were correlated with change in Beck Anxiety Inventory ( BAI ) scores , suggesting clinical relevance of these changes . Amygdala – prefrontal connectivity turned from negative coupling ( typically seen in down-regulation of emotions ) , to positive coupling ; potentially suggesting a unique mechanism of mindfulness . Findings suggest that in GAD , mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion ; these changes correspond with reported symptom improvements BACKGROUND Functional magnetic resonance imaging ( fMRI ) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial . Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex ( ACC ) . Here , we sought to determine whether pretreatment amygdala and rostral ACC ( rACC ) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder ( GAD ) . METHODS Fifteen subjects ( 12 female subjects ) with GAD participated in an open-label venlafaxine treatment trial . Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration . In addition , the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects ( 12 female subjects ) who did not have GAD and did not receive venlafaxine treatment . RESULTS The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala . These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1 ) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2 ) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group . CONCLUSIONS These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD Although the role of emotion in socioeconomic decision making is increasingly recognised , the impact of specific emotional disorders , such as anxiety disorders , on these decisions has been surprisingly neglected . Twenty anxious patients and twenty matched controls completed a commonly used socioeconomic task ( the Ultimatum Game ) , in which they had to accept or reject monetary offers from other players . Anxious patients accepted significantly more unfair offers than controls . We discuss the implication s of these findings in light of recent models of anxiety , in particular the importance of interpersonal factors and assertiveness in an integrated model of decision making . Finally , we were able to show that pharmacological serotonin used to treat anxious symptomatology tended to normalise decision making , further confirming and extending the role of serotonin in co-operation , prosocial behaviour , and social decision making . These results show , for the first time , a different pattern of socioeconomic behaviour in anxiety disordered patients , in addition to the known memory , attentional and emotional biases that are part of this pathological condition More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve . We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic , aripiprazole . We report on patients with depression and anxiety disorders , including panic disorder , generalized anxiety disorder , social anxiety and post-traumatic stress disorder , who had an incomplete response to a variety of selective serotonin reuptake inhibitors ( SSRIs ) and who received augmentation with aripiprazole . The primary outcome measure was the Clinical Global Impression of Improvement ( CGI-I ) . In the intent-to-treat analysis , the mean±SD CGI-S was 3.8±1.3 at endpoint . Fifty-nine percent of subjects received CGI-I ratings of 1 or 2 , ‘ much improved ’ or ‘ very much improved , ’ in terms of their depression and anxiety symptoms at the end of 12 weeks . Several patients showed an early ( weeks 1–5 ) , as well as sustained , response to augmentation with doses of aripiprazole between 15 and 30 mg/day . The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment . Because this is a retrospective case review , further prospect i ve studies are required to confirm these findings This study investigated the temporal pattern of brain response to emotional stimuli during 28 days of alprazolam treatment among patients with generalized anxiety disorder ( GAD ) r and omized 2:1 to drug or placebo in a double-blind design . Functional magnetic resonance imaging scans obtained during an emotion face matching task ( EFMT ) and an affective stimulus expectancy task ( STIMEX ) were performed at baseline , one hour after initial drug administration and 28 days later . Alprazolam significantly reduced scores on the Hamilton Anxiety Scale and the Penn State Worry Question naire after one week and 28 days of treatment . Brain activation in the amygdala during the EFMT and in the insula during the STIMEX was reduced one hour after alprazolam administration but returned to baseline levels at Day 28 . Exploratory analyses revealed significant treatment differences in brain activity during the STIMEX on Day 28 in frontal lobe , cau date nucleus , middle temporal gyrus , secondary visual cortex , and supramarginal gyrus . These results are consistent with the notion that the neural mechanisms supporting sustained treatment effects of benzodiazepines in GAD differ from those underlying their acute effects Some research ers have recently suggested that antidepressants may be superior to benzodiazepines in the alleviation of generalized anxiety . In a 6-week , double-blind , parallel- design study with flexible dosage scheduling , the authors compared the effects of alprazolam with those of imipramine in 60 patients who had generalized anxiety disorder . On rating scales that contained both psychic and somatic symptoms , patients in both treatment groups improved to a similar degree after 2 weeks . However , alprazolam was more effective in attenuating somatic symptoms , and imipramine was more effective in attenuating psychic symptoms such as dysphoria and negative anticipatory thinking . The authors ' results suggest that , in generalized anxiety , somatic symptoms and hyperarousal selectively respond to drugs acting on the gamma-aminobutyric acid system , whereas psychic symptoms respond to treatments affecting the noradrenergic or serotonergic systems The purpose of this study was to determine whether short-term tolerance develops to GABA-agonist-induced changes in saccadic eye movements ( SEMs ) , and whether the time course for GABA-agonist induced onset and offset of impairment is similar for SEMs and for psychomotor function . An additional goal was to determine whether there are differences in sensitivity between SEMs and psychomotor function . Six healthy volunteers participated in this balanced double-blind , three-way crossover , single-dose study of placebo and two different dosage forms of the GABA-agonist alprazolam : a rapidly absorbed oral 1.5-mg compressed tablet ( CT ) and a 3.0-mg sustained release ( SR ) tablet . Treatments were separated by a 7-day washout period . Peak concentrations did not differ between CT and SR treatments , although area under the concentration-time curve ( AUC ) of alprazolam was greater after administration of SR than after CT , because plateau concentrations were attained after SR . Both SEM and psychomotor tests showed time-dependent responses consistent with the development of tolerance . SEMs discriminated the differences in rate of drug input of the CT and SR formulations , with impairment evident at low concentrations during absorption . SEM impairment also persisted longer than did psychomotor impairment . Peak saccade velocity is a more sensitive indicator of pharmacologic effects mediated by the GABA-benzodiazepine receptor complex than are psychomotor responses . This is probably the result of the very high GABA dependency of SEMs , along with their limited sensitivity to motivation BACKGROUND The objective of this r and omized , double-blind , placebo-controlled study was to investigate the efficacy and safety of paroxetine in out patients with generalized anxiety disorder ( GAD ) . METHOD Male and female out patients 18 years and older who met DSM-IV criteria for GAD and had baseline scores of at least 20 on the Hamilton Rating Scale for Anxiety ( HAM-A ) were r and omly assigned to treatment with paroxetine ( 20 - 50 mg/day ) or placebo for 8 weeks . The primary efficacy variable was the mean change from baseline in the total score of the HAM-A. Additional key efficacy variables were the change from baseline in the scores of the HAM-A items anxious mood and tension , the anxiety subscale of the Hospital Anxiety and Depression Scale , and the Sheehan Disability Scale ( SDS ) . The proportions of patients fulfilling response and remission criteria at week 8 were also determined . RESULTS The intent-to-treat population included 324 patients . At week 8 , compared with the placebo group ( N = 163 ) , the paroxetine group ( N = 161 ) had a significantly greater reduction of GAD symptoms on all of the above-mentioned efficacy variables . On the HAM-A anxious mood item , which encompasses the cardinal symptoms of GAD , significantly greater efficacy was observed from week 1 and on the SDS significantly greater improvement was documented in the domain " social life " as early as week 4 for paroxetine compared with placebo . In both the last-observation-carried-forward and completer data sets , significantly greater proportions of paroxetine-treated patients achieved response or remission by week 8 . Treatment with paroxetine was well tolerated , and the number and type of adverse events recorded in the paroxetine group correspond to the known safety profile of this medication . CONCLUSION Paroxetine in doses of 20 to 50 mg once daily is effective in the treatment of patients with GAD . Improvement of core symptoms of GAD occurs early and is associated with significant reduction in disability after only 8 weeks of treatment BACKGROUND Generalised anxiety disorder ( GAD ) has received less study than other anxiety disorders , particularly its long-term treatment . AIMS To assess the efficacy and safety of venlafaxine extended release ( ER ) in patients with GAD . METHOD A total of 541 out- patients , 18 - 86 years old , were recruited to this 24-week , placebo-controlled , double-blind study of three fixed doses ( 37.5 , 75 and 150 mg/day ) of venlafaxine ER . RESULTS All doses of venlafaxine ER showed efficacy superior to placebo , apparent from week 2 , that was sustained throughout the 24-week study for the two higher doses . The discontinuation rate did not differ significantly among the treatment groups . CONCLUSIONS Venlafaxine ER is an effective and safe treatment for GAD for up to 6 months OBJECTIVES Generalized anxiety disorder ( GAD ) is one of the most prevalent mental disorders in the elderly , but its functional neuroanatomy is not well understood . Given the role of emotion dysregulation in GAD , we sought to describe the neural bases of emotion regulation in late-life GAD by analyzing the functional connectivity ( FC ) in the Salience Network and the Executive Control Network during worry induction and worry re appraisal . METHODS The study included 28 elderly GAD and 31 non-anxious comparison participants . Twelve elderly GAD completed a 12-week pharmacotherapy trial . We used an in-scanner worry script that alternates blocks of worry induction and re appraisal . We assessed network FC , using the following seeds : anterior insula ( AI ) , dorsolateral prefrontal cortex ( dlPFC ) , the bed nucleus of stria terminalis ( BNST ) , and the paraventricular nucleus ( PVN ) . RESULTS GAD participants exhibited greater FC during worry induction between the left AI and the right orbitofrontal cortex , and between the BNST and the subgenual cingulate . During worry re appraisal , the non-anxious participants had greater FC between the left dlPFC and the medial PFC , as well as between the left AI and the medial PFC , and elderly GAD patients had greater FC between the PVN and the amygdala . Following 12 weeks of pharmacotherapy , GAD participants had greater connectivity between the dlPFC and several prefrontal regions during worry re appraisal . CONCLUSION FC during worry induction and re appraisal points toward abnormalities in both worry generation and worry re appraisal . Following successful pharmacologic treatment , we observed greater connectivity in the prefrontal nodes of the Executive Control Network during re appraisal of worry |
2,153 | 24,727,428 | Depression remission did not predict better glycaemic control across studies .
Limited evidence from short-to-medium term RCTs predominantly conducted in the USA suggests that collaborative care for depression significantly improves both depression and glycaemia outcomes , independently , in people with comorbid depression and diabetes | OBJECTIVE The collaborative care model is recommended for depression in adults with a chronic physical health problem like diabetes .
We sought to systematic ally assess the effect of collaborative care on depression and glycaemia in adults with comorbid depression and diabetes to inform guidelines and practice . | OBJECTIVE The purpose of the study was to investigate the effect of comorbid depression on glycemic control and on response to a telemedicine case management intervention for elderly , ethnically diverse diabetic patients . RESEARCH DESIGN AND METHODS Medicare beneficiaries in underserved areas were participants ( n = 1,665 ) in the Informatics for Diabetes Education and Telemedicine ( IDEATel ) project and r and omized to a telemedicine case management intervention or usual care . The data analyzed include baseline demographics ( age , sex , race/ethnicity , marital status , insulin use , years of education , years of diabetes , and pack-years smoked ) and measures of glycemic control ( HbA(1c ) [ A1C ] ) , comorbidity , diabetes symptom severity , functional disability and depression , and 1-year ( n = 1,578 ) A1C . The association between depression and glycemic control was analyzed cross-sectionally and prospect ively . RESULTS At baseline , there was a significant correlation between depression and A1C and a trend for depression to predict A1C when other factors were controlled . However , in prospect i ve analyses , depression did not predict change in A1C , either in the control or intervention group . CONCLUSIONS In this large sample of elderly diabetic patients , a weak relationship between depression and A1C was found , but depression did not prospect ively predict change in glycemic control . Thus , there is no evidence that depression should be used to exclude patients from interventions . Also , we should evaluate the impact of depression on outcomes other than glycemic control Purpose The purpose of this study was to examine whether integrating depression treatment into care for type 2 diabetes mellitus among older African Americans improved medication adherence , glycemic control , and depression outcomes . Methods Older African Americans prescribed pharmacotherapy for type 2 diabetes mellitus and depression from physicians at a large primary care practice in west Philadelphia were r and omly assigned to an integrated care intervention or usual care . Adherence was assessed at baseline , 2 , 4 , and 6 weeks using the Medication Event Monitoring System to assess adherence . Outcomes assessed at baseline and 12 weeks included st and ard laboratory tests to measure glycemic control and the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression . Results In all , 58 participants aged 50 to 80 years participated . The proportion of participants who had 80 % or greater adherence to an oral hypoglycemic ( intervention 62.1 % vs usual care 24.1 % ) and an antidepressant ( intervention 62.1 % vs usual care 10.3 % ) was greater in the intervention group in comparison with the usual care group at 6 weeks . Participants in the integrated care intervention had lower levels of glycosylated hemoglobin ( intervention 6.7 % vs usual care 7.9 % ) and fewer depressive symptoms ( CES-D mean scores : intervention 9.6 vs usual care 16.6 ) compared with participants in the usual care group at 12 weeks . Conclusion A pilot r and omized controlled trial integrating type 2 diabetes mellitus treatment and depression was successful in improving outcomes among older African Americans . Integrated interventions may be more feasible and effective in real-world practice s with competing dem and s for limited re sources BACKGROUND Patients with depression and poorly controlled diabetes , coronary heart disease , or both have an increased risk of adverse outcomes and high health care costs . We conducted a study to determine whether coordinated care management of multiple conditions improves disease control in these patients . METHODS We conducted a single-blind , r and omized , controlled trial in 14 primary care clinics in an integrated health care system in Washington State , involving 214 participants with poorly controlled diabetes , coronary heart disease , or both and coexisting depression . Patients were r and omly assigned to the usual-care group or to the intervention group , in which a medically supervised nurse , working with each patient 's primary care physician , provided guideline -based , collaborative care management , with the goal of controlling risk factors associated with multiple diseases . The primary outcome was based on simultaneous modeling of glycated hemoglobin , low-density lipoprotein ( LDL ) cholesterol , and systolic blood-pressure levels and Symptom Checklist-20 ( SCL-20 ) depression outcomes at 12 months ; this modeling allowed estimation of a single overall treatment effect . RESULTS As compared with controls , patients in the intervention group had greater overall 12-month improvement across glycated hemoglobin levels ( difference , 0.58 % ) , LDL cholesterol levels ( difference , 6.9 mg per deciliter [ 0.2 mmol per liter ] ) , systolic blood pressure ( difference , 5.1 mm Hg ) , and SCL-20 depression scores ( difference , 0.40 points ) ( P<0.001 ) . Patients in the intervention group also were more likely to have one or more adjustments of insulin ( P=0.006 ) , antihypertensive medications ( P<0.001 ) , and antidepressant medications ( P<0.001 ) , and they had better quality of life ( P<0.001 ) and greater satisfaction with care for diabetes , coronary heart disease , or both ( P<0.001 ) and with care for depression ( P<0.001 ) . CONCLUSIONS As compared with usual care , an intervention involving nurses who provided guideline -based , patient-centered management of depression and chronic disease significantly improved control of medical disease and depression . ( Funded by the National Institute of Mental Health ; Clinical Trials.gov number , NCT00468676 . ) Objectives To determine the effectiveness of collaborative care in reducing depression in primary care patients with diabetes or heart disease using practice nurses as case managers . Design A two-arm open r and omised cluster trial with wait-list control for 6 months . The intervention was followed over 12 months . Setting Eleven Australian general practice s , five r and omly allocated to the intervention and six to the control . Participants 400 primary care patients ( 206 intervention , 194 control ) with depression and type 2 diabetes , coronary heart disease or both . Intervention The practice nurse acted as a case manager identifying depression , review ing pathology results , lifestyle risk factors and patient goals and priorities . Usual care continued in the controls . Main outcome measure A five-point reduction in depression scores for patients with moderate-to-severe depression . Secondary outcome was improvements in physiological measures . Results Mean depression scores after 6 months of intervention for patients with moderate-to-severe depression decreased by 5.7±1.3 compared with 4.3±1.2 in control , a significant ( p=0.012 ) difference . ( The plus – minus is the 95 % confidence range . ) Intervention practice s demonstrated adherence to treatment guidelines and intensification of treatment for depression , where exercise increased by 19 % , referrals to exercise programmes by 16 % , referrals to mental health workers ( MHWs ) by 7 % and visits to MHWs by 17 % . Control- practice exercise did not change , whereas referrals to exercise programmes dropped by 5 % and visits to MHWs by 3 % . Only referrals to MHW increased by 12 % . Intervention improvements were sustained over 12 months , with a significant ( p=0.015 ) decrease in 10-year cardiovascular disease risk from 27.4±3.4 % to 24.8±3.8 % . A review of patients indicated that the study 's safety protocol s were followed . Conclusions TrueBlue participants showed significantly improved depression and treatment intensification , sustained over 12 months of intervention and reduced 10-year cardiovascular disease risk . Collaborative care using practice nurses appears to be an effective primary care intervention . Trial registration ACTRN12609000333213 ( Australia and New Zeal and Clinical Trials Registry ) OBJECTIVE To determine whether evidence -based socioculturally adapted collaborative depression care improves receipt of depression care and depression and diabetes outcomes in low-income Hispanic subjects . RESEARCH DESIGN AND METHODS This was a r and omized controlled trial of 387 diabetic patients ( 96.5 % Hispanic ) with clinical ly significant depression recruited from two public safety-net clinics from August 2005 to July 2007 and followed over 18 months . Intervention ( INT group ) included problem-solving therapy and /or antidepressant medication based on a stepped-care algorithm ; first-line treatment choice ; telephone treatment response , adherence , and relapse prevention follow-up over 12 months ; plus systems navigation assistance . Enhanced usual care ( EUC group ) included st and ard clinic care plus patient receipt of depression educational pamphlets and a community re source list . RESULTS INT patients had significantly greater depression improvement ( ≥50 % reduction in Symptom Checklist-20 depression score from baseline ; 57 , 62 , and 62 % vs. the EUC group 's 36 , 42 , and 44 % at 6 , 12 , and 18 months , respectively ; odds ratio 2.46–2.57 ; P < 0.001 ) . Mixed-effects linear regression models showed a significant study group – by – time interaction over 18 months in diabetes symptoms ; anxiety ; Medical Outcomes Study Short-Form Health Survey ( SF-12 ) emotional , physical , and pain-related functioning ; Sheehan disability ; financial situation ; and number of social stressors ( P = 0.04 for disability and SF-12 physical functioning , P < 0.001 for all others ) but no study group – by – time interaction in A1C , diabetes complications , self-care management , or BMI . CONCLUSIONS Socioculturally adapted collaborative depression care improved depression , functional outcomes , and receipt of depression treatment in predominantly Hispanic patients in safety-net clinics PURPOSE Medication nonadherence , inconsistent patient self-monitoring , and inadequate treatment adjustment exacerbate poor disease control . In a collaborative , team-based , care management program for complex patients ( TEAMcare ) , we assessed patient and physician behaviors ( medication adherence , self-monitoring , and treatment adjustment ) in achieving better outcomes for diabetes , coronary heart disease , and depression . METHODS A r and omized controlled trial was conducted ( 2007–2009 ) in 14 primary care clinics among 214 patients with poorly controlled diabetes ( glycated hemoglobin [ HbA1c ] ≥8.5 % ) or coronary heart disease ( blood pressure > 140/90 mm Hg or low-density lipoprotein cholesterol > 130 mg/dL ) with coexisting depression ( Patient Health Question naire-9 score ≥10 ) . In the TEAMcare program , a nurse care manager collaborated closely with primary care physicians , patients , and consultants to deliver a treat-to-target approach across multiple conditions . Measures included medication initiation , adjustment , adherence , and disease self-monitoring . RESULTS Pharmacotherapy initiation and adjustment rates were sixfold higher for antidepressants ( relative rate [ RR ] = 6.20 ; P < .001 ) , threefold higher for insulin ( RR = 2.97 ; P < .001 ) , and nearly twofold higher for antihypertensive medications ( RR = 1.86 , P < .001 ) among TEAMcare relative to usual care patients . Medication adherence did not differ between the 2 groups in any of the 5 therapeutic classes examined at 12 months . TEAMcare patients monitored blood pressure ( RR = 3.20 ; P < .001 ) and glucose more frequently ( RR = 1.28 ; P = .006 ) . CONCLUSIONS Frequent and timely treatment adjustment by primary care physicians , along with increased patient self-monitoring , improved control of diabetes , depression , and heart disease , with no change in medication adherence rates . High baseline adherence rates may have exerted a ceiling effect on potential improvements in medication adherence Abstract Objective : To test whether a structured self-monitoring of blood glucose ( SMBG ) protocol reduces depressive symptoms and diabetes distress . Research design and methods : A 12-month , cluster-r and omised , clinical trial compared patients who received a collaborative , structured SMBG , physician/patient intervention with an active control . Studied were 483 insulin naïve type 2 diabetes patients ( experimental = 256 , control = 227 ) ( ≥ 7.5 % HbA1c ) from 34 primary care practice s ( experimental = 21 , control = 13 ) . Experimental patients used a paper tool to record a 7-point SMBG profile on each of three consecutive days prior to their quarterly physician visit . Patients and physicians interpreted SMBG results to make medication and lifestyle changes . Clinical trial registration : NIH Trial Registry Number : NCT00674986 . Main outcome measures : Depressive symptoms ( Patient Health Question naire : PHQ-8 ) , diabetes-related distress ( Diabetes Distress Scale : DDS ) . HbA1c and SMBG frequency were assessed quarterly ; data were analysed using Linear Mixed Models ( LMM ) for intent-to-treat ( ITT ) and per protocol ( PP ) analyses . Results : ITT analyses showed significant improvement in depression and disease-related distress among experimental and control patients from baseline to 12 months ( p < 0.01 in both cases ) with no between-group differences . Experimental patients displayed significantly greater reductions in distress related to regimen adherence than controls . Also , experimental patients with elevated diabetes distress or depressive symptoms at baseline showed significantly greater reductions in distress and depressive symptoms than control patients at 12 months . The greater improvement in mood in the experimental than control group was independent of improvements in glycaemic control and changes in SMBG frequency . Conclusions : Using well st and ardised measures , collaborative , structured SMBG leads to reductions , not increases , in depressive symptoms and diabetes distress over time , for the large number of moderately depressed or distressed type 2 patients in poor glycaemic control . Changes in affective status are independent of improvements in glycaemic control and changes in SMBG frequency for these patients Context Many patients have both diabetes and depression . Some hypothesize that treating depression might improve diabetes outcomes . Contribution In this r and omized trial , 12 months of depression care management for depressed patients with diabetes improved depression-related outcomes and increased the frequency of exercise . However , care management did not affect diet , diabetes medication adherence , glucose testing , or glycemic control . Caution s The study sample had reasonably good diabetes control at baseline . Whether patients with poorly controlled diabetes would benefit from depression care is not known . The Editors Major depression and dysthymic disorder affect 5 % to 10 % of older adults seen in primary care setting s ( 1 - 3 ) . Late-life depression is often chronic or recurrent ( 4 - 6 ) and is associated with substantial suffering , functional impairment , and diminished health-related quality of life ( 7 ) . Diabetes mellitus affects 7.8 % of all adults and almost 1 in 5 of those age 60 years and older ( 8) . Individuals with diabetes mellitus have a 2-fold higher rate of major depression than those without diabetes ( 9 , 10 ) . Depression adversely affects the course of coexisting medical illness , contributing to increased symptom burden , functional impairment , and mortality ( 11 , 12 ) . For patients with diabetes mellitus , depression is associated with decreased glycemic control and increased number of micro- and macrovascular complications ( 13 , 14 ) . The mechanism of effect is not understood but may be related to depression-induced abnormalities in neuroendocrine and neurotransmitter function or decreased self-care behaviors ( 15 - 20 ) . Integrating evidence -based depression care for persons with diabetes may improve both depression and diabetes outcomes . Three small r and omized , controlled trials have studied the effect of treatment for depression on affective and glycemic outcomes in patients with depression and diabetes mellitus ( 21 - 23 ) . These studies have consistently shown improvements in affective outcomes , but effects on glycemic control have been mixed . Primary care physicians are well positioned to provide integrated care for depression and diabetes mellitus but face many barriers . Controlled trials report that treatment for depression is efficacious in approximately 70 % of persons who complete treatment compared with 30 % of those who receive placebo ( 24 ) . However , these results are difficult to replicate in routine primary care practice . Barriers to high- quality care include suboptimal recognition ; inconsistent treatment with lack of close follow-up and monitoring ; and organizational barriers , such as brief visits , poor integration with specialty mental health care , competing clinical priorities , and lack of decision support systems ( 25 - 27 ) . Simple interventions , such as depression screening and physician education , have little impact on these barriers and patient outcomes ( 28 - 30 ) . Treatment models that use a depression specialist working collaboratively with primary care physicians have shown clinical ly important improvement in patient outcomes ( 31 - 37 ) . We recently reported robust effects of such a model for older adults with major depression or dysthymia ( 37 ) . In this preplanned analysis , we evaluate the effects on affective and diabetes-specific outcomes . If effective care for depression also benefits adherence to self-care regimens , functional status , and other medical illness outcomes , it would add powerful quality -of-care and economic incentives for the dissemination and maintenance of these models . In addition , if effective care for depression improves self-care behaviors , it may also positively affect other chronic medical illnesses with important self-care components . For this prespecified subgroup analysis , we focused on older adults with clinical depression and coexisting diabetes mellitus . We hypothesized that the collaborative care intervention would improve affective symptoms , functional status , self-care behaviors , and glycemic control . In addition , we hypothesized that effects on glycemic control would be greatest for patients with baseline hemoglobin A1c values of 8.0 % or greater . Methods The Improving MoodPromoting Access to Collaborative Treatment ( IMPACT ) study is a multisite r and omized , controlled trial of a collaborative care intervention program for late-life depression in primary care ( 37 , 38 ) . Institutional review boards at participating sites approved study protocol s , and all participants gave written informed consent . Patients Seven study sites representing 8 diverse health care organizations with a total of 18 primary care clinics in 5 states participated in the study . From July 1999 to August 2001 , depressed older adults were recruited through referrals from primary care practitioners and other clinic staff or through systematic depression screening with a 2-item depression screener adapted from the Primary Care Evaluation of Mental Disorders ( 39 ) . Of the 2190 patients referred to the study , 308 ( 14 % ) declined the initial eligibility screening or additional interviews , 54 ( 3 % ) had incomplete initial screenings , and 202 ( 9 % ) were ineligible because they were younger than 60 years of age or they did not plan to use the participating clinic over the coming 12 months . Of the 32908 patients approached for screening , 5246 ( 16 % ) declined the initial screening or follow-up interviews . A total of 1791 ( 5 % ) of the initial screenings were incomplete and 23233 ( 71 % ) of those screened were not eligible because they did not have one of the core depression symptoms ( 95 % ) or because of logistic reasons such as lack of transportation or access to a telephone ( 5 % ) . The remaining 1626 ( 74 % ) of those referred and 2638 ( 8 % ) of those screened completed a computer-assisted structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) , to assess whether patients met research diagnostic criteria for major depression or dysthymia ( 40 ) . Inclusion criteria were age 60 years or older , plans to use one of the participating clinics as the main source of general medical care in the coming year , and a diagnosis of current major depression or dysthymic disorder according to the structured clinical interview for DSM-IV . Otherwise eligible persons were excluded because of a current drinking problem ( a score of 2 on the CAGE question naire ) ( 41 ) , a history of bipolar disorder or psychosis ( 38 ) , ongoing treatment with a psychiatrist , or severe cognitive impairment defined by a score less than 3 on a 6-item cognitive screener ( 42 ) . We identified 2102 eligible older adults with major depression or dysthymic disorder , of whom 1801 ( 86 % ) enrolled in the study . As part of the structured baseline interview , enrolled patients were asked Has a doctor or another health care worker diagnosed you with or treated you for high blood sugar or diabetes in the past 3 years ? The 417 patients who endorsed this question are the focus of the diabetes-specific analyses . After the baseline interview , we r and omly assigned participants to the IMPACT intervention or usual care . The r and omization was stratified by recruitment method ( screening or referral ) and clinic . R and omization information was contained in a set of numbered , sealed envelopes for each stratum that were used sequentially for newly enrolled patients at each clinic ( 38 ) . Diagnoses were communicated to enrolled patients and their primary care physicians . Intervention Patients in the intervention group received a 20-minute educational videotape and a booklet about late-life depression and were encouraged to have an initial visit with a depression care manager at the primary care clinic ( 43 , 44 ) . Care managers were nurses or psychologists who were trained for the study as a depression clinical specialist ( 38 , 45 ) . During the initial visit , the depression clinical specialist conducted a clinical and psychosocial history , review ed the educational material s , and discussed patient preferences for depression treatment ( antidepressant medications or psychotherapy ) . New patients and patients needing treatment plan adjustments were discussed with a supervising team psychiatrist and a liaison primary care physician during a weekly team meeting . The depression clinical specialist then worked with the patient and his or her regular primary care provider to establish a treatment plan according to an evidence -based treatment algorithm ( 38 ) . The IMPACT algorithm suggested an initial choice of an antidepressant ( usually a selective serotonin reuptake inhibitor ) or a course of Problem-Solving Treatment in Primary Care ( PST-PC ) , which consisted of 6 to 8 brief sessions of structured psychotherapy for depression , delivered by the depression clinical specialist in primary care ( 46 - 49 ) . For patients who were already receiving antidepressant medications but who were still depressed , the recommendation for partial responders was to increase the dose or augment the antidepressant with a trial of PSTPC ; the recommendation for nonresponders was to switch to a different medication or use a trial of PSTPC . Depression clinical specialists also encouraged patients to increase behavioral activation and referred them to additional health or social services , as clinical ly indicated . The intervention did not specifically address diabetes mellitus or other coexisting medical illnesses . As care managers , depression clinical specialists attempted to follow patients for up to 12 months ; they monitored treatment response with the Primary Care Evaluation of Mental Disorders Patient Health Question naire ( 50 ) and a Web-based clinical information system ( 51 ) . During the acute treatment phase , in-person or telephone follow-up contacts were suggested at least every other week . Patients who recovered from depression ( 50 % reduction in the Patient Health Question naire score and <3 of 9 symptoms of major depression ) were engaged in developing a relapse prevention plan and were then Abstract Objectives : To evaluate integrated care for diabetes in clinical , psychosocial , and economic terms . Design : Pragmatic r and omised trial . Setting : Hospital diabetic clinic and three general practice groups in Grampian . Patients : 274 adult diabetic patients attending a hospital clinic and registered with one of three general practice s. Intervention - R and om allocation to conventional hospital clinic care or integrated care . Integrated care patients seen in general practice every three or four months and in the hospital clinic annually . General practitioners were given written guidelines for integrated care . Main outcome measures : Metabolic control , psychosocial status , knowledge of diabetes , beliefs about control of diabetes , satisfaction with treatment , disruption of normal activities , numbers of consultations and admissions , frequency of metabolic monitoring , costs to patients and NHS . Results - A higher proportion of patients defaulted from conventional care ( 14 ( 10 % ) ) than from integrated care ( 4 ( 3 % ) , 95 % confidence interval of difference 2 % to 13 % ) . After two years no significant differences were found between the groups in metabolic control , psychosocial status , knowledge , beliefs about control , satisfaction with treatment , unscheduled admissions , or disruption of normal activities . Integrated care was as effective for insulin dependent as non-insulin dependent patients . Patients in integrated care had more visits and higher frequencies of examination . Costs to patients were lower in integrated care ( mean pounds sterling 1.70 ) than in conventional care ( pounds sterling 8) . 88 % of patients who experienced integrated care wished to continue with it . Conclusions : This model of integrated care for diabetes was at least as effective as conventional hospital clinic care Objective To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life . Design A r and omised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and /or risk factors for coronary heart disease compared with usual care among middle aged and elderly people Setting Fourteen primary care clinics in Seattle , Washington . Participants Patients with diabetes or coronary heart disease , or both , and blood pressure above 140/90 mm Hg , low density lipoprotein concentration > 3.37 mmol/L , or glycated haemoglobin 8.5 % or higher , and PHQ-9 depression scores of ≥10 . Intervention A 12 month intervention to improve depression , glycaemic control , blood pressure , and lipid control by integrating a “ treat to target ” programme for diabetes and risk factors for coronary heart disease with collaborative care for depression . The intervention combined self management support , monitoring of disease control , and pharmacotherapy to control depression , hyperglycaemia , hypertension , and hyperlipidaemia . Main outcome measures Social role disability ( Sheehan disability scale ) , global quality of life rating , and World Health Organization disability assessment schedule ( WHODAS-2 ) scales to measure disabilities in activities of daily living ( mobility , self care , household maintenance ) . Results Of 214 patients enrolled ( 106 intervention and 108 usual care ) , disability and quality of life measures were obtained for 97 intervention patients at six months ( 92 % ) and 92 at 12 months ( 87 % ) , and for 96 usual care patients at six months ( 89 % ) and 92 at 12 months ( 85 % ) . Improvements from baseline on the Sheehan disability scale ( −0.9 , 95 % confidence interval −1.5 to −0.2 ; P=0.006 ) and global quality of life rating ( 0.7 , 0.2 to 1.2 ; P=0.005 ) were significantly greater at six and 12 months in patients in the intervention group . There was a trend toward greater improvement in disabilities in activities of daily living ( −1.5 , −3.3 to 0.4 ; P=0.10 ) . Conclusions Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life . Trial registration Clinical Trials NCT00468676 Background When depression accompanies diabetes , it complicates treatment , portends worse outcomes and increases health care costs . A collaborative care case-management model , previously tested in an urban managed care organization in the US , achieved significant reduction of depressive symptoms , improved diabetes disease control and patient-reported outcomes , and saved money . While impressive , these findings need to be replicated and extended to other healthcare setting s. Our objective is to comprehensively evaluate a collaborative care model for comorbid depression and type 2 diabetes within a Canadian primary care setting . Methods / design We initiated the TeamCare model in four Primary Care Networks in Northern Alberta . The intervention involves a nurse care manager guiding patient-centered care with family physicians and consultant physician specialists to monitor progress and develop tailored care plans . Patients eligible for the intervention will be identified using the Patient Health Question naire-9 as a screen for depressive symptoms . Care managers will then guide patients through three phases : 1 ) improving depressive symptoms , 2 ) improving blood glucose , blood pressure and cholesterol , and 3 ) improving lifestyle behaviors . We will employ the RE- AIM framework for a comprehensive and mixed- methods approach to our evaluation . Effectiveness will be assessed using a controlled “ on-off ” trial design , whereby eligible patients would be alternately enrolled in the TeamCare intervention or usual care on a monthly basis . All patients will be assessed at baseline , 6 and 12 months . Our primary analyses will be based on changes in two outcomes : depressive symptoms , and a multivariable , scaled marginal model for the combined outcome of global disease control ( i.e. , A1c , systolic blood pressure , LDL cholesterol ) . Our planned enrolment of 168 patients will provide greater than 80 % power to observe clinical ly important improvements in all measured outcomes . Direct costing of all intervention components and measurement of all health care utilization using linked administrative data bases will be used to determine the cost-effectiveness of the intervention relative to usual care . Discussion Our comprehensive evaluation will generate evidence to reliability , effectiveness and sustainability of this collaborative care model for patients with chronic diseases and depression . Trials registration Clintrials.gov Identifier : OBJECTIVE To examine the association between soft drink consumption and mental health problems , including self-reported doctor-diagnosed anxiety , stress-related problem and depression , suicidal ideation and psychological distress , among adults in South Australia . DESIGN Data were collected using a risk factor surveillance system . Each month a representative r and om sample of South Australians was selected from the Electronic White Pages with interviews conducted using computer-assisted telephone interviewing . SETTING South Australia . SUBJECTS Participants were aged 16 years and above . RESULTS Among 4741 participants , 12.5 % reported daily soft drink consumption of more than half a litre . High levels of soft drink consumption were positively associated with depression , stress-related problem , suicidal ideation , psychological distress and a current mental health condition , but not anxiety . Overall , 24.0 % of those having suicidal ideation reported consuming more than half a litre of soft drink per day . In the multivariate analysis , after adjusting for sociodemographic and lifestyle factors , those who consumed more than half a litre of soft drink per day had approximately 60 % greater risk of having depression , stress-related problem , suicidal ideation , psychological distress or a current mental health condition , compared with those not consuming soft drinks . The soft drink to total fluid consumption ratio had similar associations with mental health problems . CONCLUSIONS There is a positive association between consumption of soft drinks and mental health problems among adults in South Australia Background : : Depression is associated with poor glycemic control , increased number of microvascular and macrovascular complications , functional impairment , mortality , and 4.5 times higher total health care costs in patients with diabetes . Shared medical appointments ( SMAs ) may be an effective method to attain national guideline recommendations for glycemic control in diabetes for patients with depression through peer support , counseling , problem solving , and improved access to care . Objective : To test the efficacy as assessed by attainment of a hemoglobin A1c ( A1C ) < 7 % of pharmacistted group SMA visits , Veterans Affairs Multidisciplinary Education in Diabetes and Intervention for Cardiac Risk Reduction in Depression ( VA-MEDIC-D ) , in patients with type 2 diabetes mellitus . Methods : This was a r and omized controlled trial of VA-MEDIC-D added to st and ard care versus st and ard care alone in depressed patients with diabetes with A1C > 6.5 % . VA-MEDIC-D consisted of 4 once-weekly , 2-hour sessions followed by 5 monthly 90-minute group sessions . Each SMA session consisted of multidisciplinary education and pharmacist-led behavioral and pharmacologic interventions for diabetes , lipids , smoking , and blood pressure . No pharmacologic interventions for depression were provided . The change in the proportion of participants who achieved an A1C < 7 % at 6 months was compared . Results : Compared to st and ard care ( n = 44 ) , a lower proportion of patients in VA-MEDIC-D ( n = 44 ) had systolic blood pressure ( SBP ) < 130 mm Hg at baseline , but were similar in other cardiovascular risk factors and psychiatric comorbidity . The change in the proportion of participants achieving an A1C < 7 % was greater in the VA-MEDIC-D arm than in the st and ard care arm ( 29.6 % vs 11.9 % ) , with odds ratio 3.6 ( 95 % CI 1.1 to 12.3 ) . VA-MEDIC-D participants also achieved significant reductions in SBP , low-density lipoprotein cholesterol , and non – high-density lipoprotein ( HDL ) cholesterol from baseline , whereas significant reductions were attained only in non – HDL cholesterol with st and ard care . There was no significant change in depressive symptoms for either arm . Conclusions : Pharmacist-led group SMA visits are efficacious in attainment of glycemic control in patients with diabetes and depression without change in depression symptoms Purpose : We sought to determine whether relationship style in patients with diabetes receiving depression treatment is associated with differential quality of care and depression outcomes . Methods : From 9 health maintenance organization clinics , 324 primary care patients with diabetes and comorbid major depression and /or dysthymia participated in the Pathways r and omized controlled trial of collaborative care for depression ( n = 160 ) versus usual care ( n = 164 ) . The intervention provided outreach , enhanced support of antidepressant medication use , and problem-solving treatment delivered by nurse case managers . Using attachment theory principles , we categorized patients as having an independent ( n = 190 ) or interactive ( n = 134 ) relationship style . We assessed whether patient relationship style moderated treatment group differences in quality of care and depression outcomes . Results : Among independent relationship style patients , the intervention result ed in significantly greater satisfaction with depression care in the first 6 months and 47 more depression-free days ( P < 0.0003 ) based on the Hopkins Symptom Checklist at 12 months , compared with usual care . There were no significant treatment group differences in satisfaction with care or depression outcomes among patients with interactive relationship style . Among patients receiving the intervention , those with an independent relationship style received significantly more problem-solving treatment sessions as compared with patients with an interactive relationship style . Conclusion : Among depressed patients with diabetes , the Pathways collaborative care intervention improved quality of care for depression compared with usual care in both relationship style groups but was associated with significantly better depressive outcomes and greater satisfaction with care compared with usual care in patients with independent but not interactive relationship style Background : This study evaluated a multifaceted psychiatric intervention targeted at the complex medically ill identified by means of the INTERMED , an instrument to assess case complexity . Methods : Of 885 rheumatology in patients and diabetes out patients who were assessed for eligibility , 247 were identified as complex ( INTERMED score > 20 ) and r and omized to the intervention ( n = 125 , 84 rheumatology and 41 diabetes patients ) or care as usual ( n = 122 , 78 rheumatology and 44 diabetes patients ) . For the majority of the cases the multifaceted intervention consisted of an intervention conducted by a psychiatric liaison nurse and /or of referral to a liaison psychiatrist , followed by advice to the treating physician or organization of a multidisciplinary case conference . Baseline and follow-up at months 3 , 6 , 9 and 12 measured prevalence of major depression ( Mini-International Neuropsychiatric Interview ) , depressive symptoms ( Center for Epidemiological Studies Depression Rating Scale ) , physical and mental health ( SF-36 ) , quality of life ( EuroQol ) , health care utilization and HbA1c levels ( diabetic patients ) . Results : Prevalence of major depression was reduced from 61 % ( T0 ) to 28 % ( T4 ) in the intervention group and remained stable in care as usual ( 57 % at T0 to 50 % at T4 ) . Compared to care as usual , significant improvement over time was observed in the intervention group with regard to depressive symptoms ( F = 11.9 ; p = 0.001 ) , perception of physical ( F = 5.7 ; p = 0.018 ) and mental health ( F = 3.9 ; p = 0.047 ) and quality of life ( F = 21.8 ; p < 0.001 ) . Effects tended to be stronger in diabetes patients , in patients with baseline major depression and in patients with moderate INTERMED scores . Finally , hospital admissions occurred less often in the intervention group , reaching statistical significance for the period between 6 and 9 months of follow-up ( p = 0.02 ) . Conclusions : The results suggest that a psychiatric intervention targeted for complex medical patients can improve health outcomes BACKGROUND There is a high prevalence of depression in patients with diabetes mellitus . Depression has been shown to be associated with poor self-management ( adherence to diet , exercise , checking blood glucose levels ) and high hemoglobin A1c ( HbA1c ) levels in patients with diabetes . OBJECTIVE To determine whether enhancing quality of care for depression improves both depression and diabetes outcomes in patients with depression and diabetes . DESIGN R and omized controlled trial with recruitment from March 1 , 2001 , to May 31 , 2002 . SETTING Nine primary care clinics from a large health maintenance organization . PARTICIPANTS A total of 329 patients with diabetes mellitus and comorbid major depression and /or dysthymia . Intervention Patients were r and omly assigned to the Pathways case management intervention ( n = 164 ) or usual care ( n = 165 ) . The intervention provided enhanced education and support of antidepressant medication treatment prescribed by the primary care physician or problem-solving therapy delivered in primary care . MAIN OUTCOME MEASURES Independent blinded assessment s at baseline and 3 , 6 , and 12 months of depression ( Hopkins Symptom Checklist 90 ) , global improvement , and satisfaction with care . Automated clinical data were used to evaluate adherence to antidepressant regimens , percentage receiving specialty mental health visits , and HbA1c levels . RESULTS When compared with usual care patients , intervention patients showed greater improvement in adequacy of dosage of antidepressant medication treatment in the first 6-month period ( odds ratio [ OR ] , 4.15 ; 95 % confidence interval [ CI ] , 2.28 - 7.55 ) and the second 6-month period ( OR , 2.90 ; 95 % CI , 1.69 - 4.98 ) , less depression severity over time ( z = 2.84 , P = .004 ) , a higher rating of patient-rated global improvement at 6 months ( intervention 69.4 % vs usual care 39.3 % ; OR , 3.50 ; 95 % CI , 2.16 - 5.68 ) and 12 months ( intervention 71.9 % vs usual care 42.3 % ; OR , 3.50 ; 95 % CI , 2.14 - 5.72 ) , and higher satisfaction with care at 6 months ( OR , 2.01 ; 95 % CI , 1.18 - 3.43 ) and 12 months ( OR , 2.88 ; 95 % CI , 1.67 - 4.97 ) . Although depressive outcomes were improved , no differences in HbA1c outcomes were observed . CONCLUSION The Pathways collaborative care model improved depression care and outcomes in patients with comorbid major depression and /or dysthymia and diabetes mellitus , but improved depression care alone did not result in improved glycemic control AIMS The aim of this study was to examine whether a nurse-administered minimal psychological intervention for depressive symptoms improves diabetes-specific quality of life and glycaemic control in older persons with diabetes . BACKGROUND Depression is common among persons with diabetes and may have a negative impact on diabetes . Interventions aim ed at reducing depressive symptoms may positively influence diabetes-specific quality of life as well . METHODS A pragmatic , r and omized controlled trial was carried out comparing the intervention with usual care among 208 Dutch primary care patients of ≥60 years with type 2 diabetes and co-occurring minor to moderate depression . Data on symptom distress and emotional distress were collected during 2003 - 2006 , and haemoglobin A1c levels were obtained from general practice s. Data were analysed using mixed model , repeated measures ANCOVAS . Hba1c was collected retrospectively from general practice s between December 2006-February 2007 . In July 2007 we retrieved some additional HbA1c data from the medical records of the university hospital . RESULTS Only in higher-educated persons did the intervention have statistically significant effect on both emotional distress and symptom distress ( DSC-R total score at 9 months P=0.001 ; PAID , 9 months P=0.03 ) . Furthermore , we found an effect on symptom distress in men ( 9 months P=0.01 ) , and on emotional distress in persons with a shorter diabetes duration ( < 7 years ) ( 9 months P=0.04 ) . A significant trend over time for haemoglobin A1c was found in favour of the intervention , with a statistically significant difference between groups after 9 months ( P=0.02 ) . CONCLUSION The nurse-administered intervention had limited effects on diabetes-specific quality of life . As only certain subgroups benefited , ways of increasing effectiveness in other groups should be explored . The potentially beneficial effect on glycaemic control is encouraging and needs further research because of small numbers in the analysis CONTEXT Patients with depression and poorly controlled diabetes mellitus , coronary heart disease ( CHD ) , or both have higher medical complication rates and higher health care costs , suggesting that more effective care management of psychiatric and medical disease control might also reduce medical service use and enhance quality of life . OBJECTIVE To evaluate the cost-effectiveness of a multicondition collaborative treatment program ( TEAMcare ) compared with usual primary care ( UC ) in out patients with depression and poorly controlled diabetes or CHD . DESIGN R and omized controlled trial of a systematic care management program aim ed at improving depression scores and hemoglobin A(1c ) ( HbA(1c ) ) , systolic blood pressure ( SBP ) , and low-density lipoprotein cholesterol ( LDL-C ) levels . SETTING Fourteen primary care clinics of an integrated health care system . PATIENTS Population -based screening identified 214 adults with depressive disorder and poorly controlled diabetes or CHD . INTERVENTION Physician-supervised nurses collaborated with primary care physicians to provide treatment of multiple disease risk factors . MAIN OUTCOME MEASURES Blinded assessment s evaluated depressive symptoms , SBP , and HbA(1c ) at baseline and at 6 , 12 , 18 , and 24 months . Fasting LDL-C concentration was assessed at baseline and at 12 and 24 months . Health plan accounting records were used to assess medical service costs . Quality -adjusted life-years ( QALYs ) were assessed using a previously developed regression model based on intervention vs UC differences in HbA(1c ) , LDL-C , and SBP levels over 24 months . RESULTS Over 24 months , compared with UC controls , intervention patients had a mean of 114 ( 95 % CI , 79 to 149 ) additional depression-free days and an estimated 0.335 ( 95 % CI , -0.18 to 0.85 ) additional QALYs . Intervention patients also had lower mean outpatient health costs of $ 594 per patient ( 95 % CI , -$3241 to $ 2053 ) relative to UC patients . CONCLUSIONS For adults with depression and poorly controlled diabetes , CHD , or both , a systematic intervention program aim ed at improving depression scores and HbA(1c ) , SBP , and LDL-C levels seemed to be a high-value program that for no or modest additional cost markedly improved QALYs . TRIAL REGISTRATION clinical trials.gov Identifier : OBJECTIVE There have been few comparisons of the effectiveness of collaborative depression care between older versus younger adults with comorbid illness , particularly among low-income population s. DESIGN Intent-to-treat analyses are conducted on pooled data from three r and omized controlled trials that tested collaborative care aim ed at improving depression , quality of life , and treatment receipt . SETTING S Trials were conducted in oncology and primary care safety net clinics and diverse home healthcare programs . PARTICIPANTS Thous and eighty-one patients with major depressive symptoms and cancer , diabetes , or other comorbid illness . INTERVENTION Similar intervention protocol s included patient , provider , sociocultural , and organizational adaptations . MEASUREMENTS The Patient Health Question naire (PHQ)-9 depression , Short-Form Health Survey-12/20 quality of life , self-reported hospitalization , ER , intensive care unit utilization , and antidepressant , psychotherapy treatment receipt are assessed at baseline , 6 , and 12 months . RESULTS There are no significant differences in reducing depression symptoms ( p ranged 0.18 - 0.58 ) , improving quality of life ( t = 1.86 , df = 669 , p = 0.07 for physical functioning at 12 months , and p ranged 0.23 - 0.99 for all others ) patients aged between > /=60 years versus 18 - 59 years . Both age group intervention patients have significantly higher rates of a 50 % PHQ-9 reduction ( older : Wald chi[df = 1 ] = 4.82 , p = 0.03 ; younger : Wald chi[df = 1 ] = 6.47 , p = 0.02 ) , greater reduction in major depression rates ( older : Wald chi[df = 1 ] = 7.72 , p = 0.01 ; younger : Wald chi[df = 1 ] = 4.0 , p = 0.05 ) than enhanced-usual-care patients at 6 months and no significant age group differences in treatment type or intensity . CONCLUSION Collaborative depression care in individuals with comorbid illness is as effective in reducing depression in older patients as younger patients , including among low-income , minority patients . Patient , provider , and organizational adaptations of depression care management models may contribute to positive outcomes OBJECTIVE To evaluate the cost-effectiveness of a socioculturally adapted collaborative depression care program among low-income Hispanics with diabetes . RESEARCH DESIGN AND METHODS A r and omized controlled trial of 387 patients with diabetes ( 96.5 % Hispanic ) with clinical ly significant depression followed over 18 months evaluated the cost-effectiveness of the Multifaceted Diabetes and Depression Program aim ed at increasing patient exposure to evidence -based depression psychotherapy and /or pharmacotherapy in two public safety net clinics . Patient medical care costs and utilization were captured from Los Angeles County Department of Health Services cl aims records . Patient-reported outcomes included Short-Form Health Survey-12 and Patient Health Question naire-9-calculated depression-free days . RESULTS Intervention patients had significantly greater Short-Form Health Survey-12 utility improvement from baseline compared with controls over the 18-month evaluation period ( 4.8 % ; P < 0.001 ) and a corresponding significant improvement in depression-free days ( 43.0 ; P < 0.001 ) . Medical cost differences were not statistically significant in ordinary least squares and log-transformed cost regressions . The average costs of the Multifaceted Diabetes and Depression Program study intervention were $ 515 per patient . The program 's cost-effectiveness averaged $ 4053 per quality -adjusted life-year per MDDP recipient and was more than 90 % likely to fall below $ 12,000 per quality -adjusted life-year . CONCLUSIONS Socioculturally adapted collaborative depression care improved utility and quality of life in predominantly low-income Hispanic patients with diabetes and was highly cost-effective PURPOSE Depression commonly accompanies diabetes , result ing in reduced adherence to medications and increased risk for morbidity and mortality . The objective of this study was to examine whether a simple , brief integrated approach to depression and type 2 diabetes mellitus ( type 2 diabetes ) treatment improved adherence to oral hypoglycemic agents and antidepressant medications , glycemic control , and depression among primary care patients . METHODS We undertook a r and omized controlled trial conducted from April 2010 through April 2011 of 180 patients prescribed pharmacotherapy for type 2 diabetes and depression in primary care . Patients were r and omly assigned to an integrated care intervention or usual care . Integrated care managers collaborated with physicians to offer education and guideline -based treatment recommendations and to monitor adherence and clinical status . Adherence was assessed using the Medication Event Monitoring System ( MEMS ) . We used glycated hemoglobin ( HbA1c ) assays to measure glycemic control and the 9-item Patient Health Question naire ( PHQ-9 ) to assess depression . RESULTS Intervention and usual care groups did not differ statistically on baseline measures . Patients who received the intervention were more likely to achieve HbA1c levels of less than 7 % ( intervention 60.9 % vs usual care 35.7 % ; P < .001 ) and remission of depression ( PHQ-9 score of less than 5 : intervention 58.7 % vs usual care 30.7 % ; P < .001 ) in comparison with patients in the usual care group at 12 weeks . CONCLUSIONS A r and omized controlled trial of a simple , brief intervention integrating treatment of type 2 diabetes and depression was successful in improving outcomes in primary care . An integrated approach to depression and type 2 diabetes treatment may facilitate its deployment in real-world practice s with competing dem and s for limited re sources |
2,154 | 20,091,608 | There was no significant difference in the mortality , graft rejection , or in re-transplantation between intervention and control in any of the comparisons that reported these outcomes .
None of the trials reported liver decompensation or quality of life .
Life-threatening adverse effects were not reported in either group in any of the comparisons .
Considering the lack of clinical benefit and the frequent adverse effects , there is currently no evidence to recommend antiviral treatment for recurrent liver graft infection with HCV . | BACKGROUND Antiviral therapy to treat recurrent hepatitis C infection after liver transplantation is controversial due to unresolved balance between benefits and harms .
OBJECTIVES To compare the therapeutic benefits and harms of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation . | Hepatitis C is the most common indication for liver transplantation ( LT ) in the United States . Recurrence of hepatitis C virus ( HCV ) infection post-LT remains a problem for which there is no completely satisfactory treatment . The aim of the present study is to evaluate mycophenolate mofetil ( MMF ) , which has both immunosuppressive and antiviral properties , to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival . Between August 1995 and May 1998 , a total of 106 patients who were HCV positive before LT were r and omized to tacrolimus ( TAC ) and prednisone versus TAC , prednisone , and MMF therapy . The rate of recurrence of HCV , patient and graft survival , incidences of rejection , and histological findings were examined . Fifty six patients were r and omized to TAC and steroid therapy ( double [ D ] drug ; group D ) , and 50 patients were r and omized to TAC , steroid , and MMF therapy ( triple [ T ] drug ; group T ) . Liver biopsies were performed when liver function was abnormal ; protocol liver biopsies were not performed . Mean follow-up was 4.3 + /- 0.8 years . Actuarial patient survivals at 4 years were 72.6 % in group D and 73.8 % in group T ( P = not significant ) . Actuarial graft survivals at 4 years were 65.6 % in group D and 65.4 % in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV . One patient in each group died of recurrent HCV without re-LT . Twenty-six patients in group D ( 46.4 % ) and 23 patients in group T ( 46.0 % ) showed signs of recurrent HCV . Mean hepatitis activity index ( HAI ) scores were 7.4 + /- 2.7 in group D and 7.0 + /- 3.4 in group T , and mean fibrosis scores were 2.9 + /- 1.7 in group D and 2.6 + /- 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period . None of these values reached statistical significance . Rates of HCV recurrence , graft loss or death from recurrent HCV , and 4-year actuarial patient and graft survival were not different between the groups . In liver transplant recipients with HCV , MMF has no impact on patient survival , graft survival , rejection , or rate of HCV recurrence based on biochemical changes and histological findings . In addition , there was no difference in HAI or fibrosis score between the two groups . Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its antiviral effect in the clinical setting Background . In this article , we explore the virological response to two types of interferon based treatment in recurrent hepatitis C virus in liver recipients who received thymoglobulin induction . Methods . Fifty consecutive patients were r and omized to receive PEG interferon alpha 2b ( 1.0 & mgr;g/kg per week ) , ribavirin ( 800 mg/d ) plus amantadine ( 200 mg/d ) , or PEG interferon alpha 2b ( 1.0 & mgr;g/kg per week ) plus ribavirin ( 800 mg/d ) . The primary endpoint was absence of hepatitis C virus RNA 6 months posttreatment . The secondary endpoint was change in fibrosis at 1 year . Results . Only 30 patients completed 1 year of treatment . In an intention to treat analysis , the sustained virological response ( SVR ) rate was 26 % in I/R/A group and 50 % in I/R group . By per protocol , the overall SVR rate was 57 % . Fibrosis progression by at least one stage was noted in 37 % patients . Twenty-nine percent of patients who achieved SVR had shown fibrosis progression by at least one stage whereas 46 % nonresponders showed fibrosis progression ( P = NS ) . Conclusion . This is the first study exploring the efficacy of pegylated interferon-based antiviral treatment in patients who received a steroid-free protocol . Our data is encouraging and shows that if liver transplant recipients can tolerate treatment for 1 year there is a reasonable chance of SVR OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials The aim of the study was to observe the frequency of neutropenia during Pegylated Interferon/Ribavirin therapy in patient with chronic hepatitis C ; to compare the efficacy of two strategies of management of neutropenia -- with Interferon dose modification and with Neupogen administration ; to compare the effectiveness rate of sustained viral response ( SVR ) in patients with Pegylated Interferon dose modification and in patients treated by using granulocyte colony-stimulating factor G-CSF-filgrastim . ( Neupogen ) . Study enrolled 47 patients with chronic active hepatitis C , aged 23 - 64 . ( 38 male and 9 female ) . All patients had HCV genotype 1b . Significant neurtopenia ( ANC<750 mm3 ) and severe neurtopenia ( ANC<500 mm3 ) developed in 41 of 47 patients ( 87 % ) . 41 patients with neurtopenia were r and omized into two groups . The first group--22 patients who received granulocyte colony-stimulating factor ( G-CSF , or filgrastim ) 300 mcg s/c weekly for correction of neutropenia and the second group--19 patients treated either with Interferon dose reduction or temporarily inhibit of Interferon treatment . In all 22 patients of the first group neutropenia was normalized without reduction and /or inhibit of Pegylated interferon . Neupogen was well tolerated and in all 22 patients the improvement of quality of life ( QOL ) was observed . It was concluded that dose reduction or temporary inhibit of Pegylated Interferon in the second group negatively acts on antiviral treatment response in patients with HCV genotype 1 . In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose ( without reduction ) . Neupogen has the potential to improve adherence rates , which may in turn improve SVR Ischemic preconditioning ( IPC ) has the potential to decrease graft injury and morbidity after liver transplantation . We prospect ively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers r and omized 1:1 to st and ard ( STD ) recovery ( N = 28 ) or IPC ( N = 34 ) . Safety was assessed by measurement of heart rate , blood pressure , and visual inspection of abdominal organs during recovery , and efficacy by recipient aminotransferases ( aspartate aminotransferase [ AST ] and alanine aminotransferase [ ALT ] , both measured in U/L ) , total bilirubin , and international normalized ratio of prothrombin time ( INR ) after transplantation . IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion . Recipient median AST , median ALT , and mean INR , in STD vs. IPC were as follows : day 1 AST 696 vs. 841 U/L ; day 3 AST 183 vs. 183 U/L ; day 1 ALT 444 vs. 764 U/L ; day 3 ALT 421 vs. 463 U/L ; day 1 INR 1.7 + /- .4 vs. 2.0 + /- .8 ; and day 3 INR 1.3 + /- .2 vs. 1.4 + /- .3 ; all P > .05 . No instances of nonfunction occurred . The 6-month graft and patient survival STD vs. IPC were 82 vs. 91 % and median hospital stay was 10 vs. 8 days ; both P > .05 . In conclusion , deceased donor livers tolerated 5 minutes of hilar clamping well , but IPC did not decrease graft injury . Further trials with longer periods of preconditioning such as 10 minutes are needed BACKGROUND & AIMS Recurrence of hepatitis C virus ( HCV ) infection is a relevant problem of liver transplantation programs . We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients . METHODS Patients with mild hepatitis C recurrence ( fibrosis stage F0 to F2 , n = 54 ) were r and omized to no treatment ( group A , n = 27 ) or peginterferon alfa-2b/ribavirin for 48 weeks ( group B , n = 27 ) . Patients with severe recurrence ( F3 to F4 , cholestatic hepatitis ) were treated ( group C , n = 27 ) . All patients ( n = 81 ) underwent a liver biopsy at baseline and after follow-up ; paired hepatic venous pressure gradient ( HVPG ) measurements were available in 51 patients . RESULTS Thirteen ( 48 % ) patients of group B and 5 ( 18.5 % ) of group C achieved sustained virological response . Liver fibrosis progressed > or = 1 stage in 40 ( 49 % ) of 81 patients : 19 ( 70 % ) of group A versus 7 ( 26 % ) of group B ( P = .001 ) and in 14 ( 54 % ) of group C. HVPG increased ( 6.5 to 13 mm Hg , P < .01 ) in patients in whom fibrosis worsened , whereas it decreased ( 5 to 3.5 mm Hg , P = .017 ) or remained unchanged in those with fibrosis improvement or stabilization , respectively . The only variable independently associated with fibrosis improvement/stabilization was treatment ( odds ratio [ OR ] = 3.7 , 95 % confidence interval [ CI ] 1.3 to 10 , P = .009 ) . Among treated patients , alanine aminotransferase ( ALT ) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization ( OR 5.3 , 95 % CI 1.5 to 18 , P < .01 ; OR 7.4 , 95 % CI 1.4 to 38 , P = .01 ; respectively ) . CONCLUSIONS Our data demonstrate that in liver transplantation recipients , antiviral therapy slows disease progression ( particularly in sustained virological responders ) , as shown by its effects on liver histology and on HVPG Allograft reinfection with hepatitis C virus ( HCV ) in transplant recipients occurs commonly and represents a major concern in the transplant setting . Suppression of viral replication in HCV transplant patients should prevent or delay progression to cirrhosis and graft failure . In this ongoing study , we present preliminary data from a prospect i ve trial of st and ard interferon ( IFN ) alpha-2b ( 2 million units daily ) for 3 months and subsequent peginterferon ( PEG IFN ) alpha-2b ( 1.5 microg/kg/week ) for 9 months . IFN therapy was combined with ribavirin ( 10 to 12 mg/kg ) . So far , HCV has become undetectable by qualitative PCR in 33 % of patients while 25 % had a reduction of HCV RNA to undetectable by the bDNA assay and 42 % had no virological response after 6 months of therapy . A biochemical response was detected in 42 % of patients . Improvement of inflammatory activity was observed in 42 % of patients after 6 months . In three patients anemia necessitated administration of erythropoietin and three patients received granulocyte-colony stimulating factor ( G-CSF ) due to leucopenia [ corrected ] In conclusion , we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b therapy in combination with ribavirin provides biochemical and virological benefits in transplant recipients with established recurrent HCV infection BACKGROUND / AIMS HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis . Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting . METHODS Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600 - 800 mg/day . Planned duration of treatment was 24 or 48 weeks according to HCV genotype . Patients who failed to respond at week 24 were considered as non-responders . RESULTS 61 patients were enrolled . According to intention-to-treat analysis , 44 ( 72 % ) patients were considered as treatment failure ( 31 non-responders , 4 relapsers , 9 dropout ) . Sustained virological response was achieved in 17 cases ( 28 % ) . Genotype 2 , higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response . In the follow up , patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure ( chi2=6.9 ; P<0.01 ) . CONCLUSIONS Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed . Sustained virological response improves patient survival The effect of ischemic preconditioning ( IPC ) in orthotopic liver transplantation ( OLT ) has not yet been clarified . We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors r and omly assigned to receive ( IPC+ group , n = 23 ) or not ( IPC- group , n = 24 ) IPC ( 10-min ischemia + 15-min reperfusion ) . In 10 cases in the IPC+ group and in 12 in the IPC- group , the expression of inducible nitric oxide synthase ( iNOS ) , neutrophil infiltration , and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies . Median aspartate aminotransferase ( AST ) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 ( 398 vs. 1,234 U/L , P = 0.002 ; and 283 vs. 685 U/L , P = 0.009 ) . Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1 , 2 , and 3 ( 333 vs. 934 U/L , P = 0.016 ; 492 vs. 1,040 U/L , P = 0.008 ; and 386 vs. 735 U/L , P = 0.022 ) . Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks , incidence of graft nonfunction and graft and patient survival rates were similar between groups . Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups . iNOS was higher postreperfusion vs. prereperfusion in the IPC- group ( P = 0.008 ) . Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups ( IPC+ , P = 0.007 ; IPC- , P = 0.003 ) . Prereperfusion and postreperfusion apoptosis was minimal in both groups . In conclusion , IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis , but it showed no clinical benefits BACKGROUND AND AIMS Hepatitis C virus ( HCV ) reinfection after liver transplantation is frequent and leads to chronic hepatitis and cirrhosis . The use of antiviral therapy in this situation remains controversial . This study aim ed to assess the safety and efficacy of interferon alfa-2b plus ribavirin for recurrent hepatitis C following liver transplantation . METHODS Transplant recipients with recurrent chronic hepatitis C were r and omized to receive either no treatment or therapy with interferon alfa-2b ( 3 MU 3 times a week ) plus 1000 - 1200 mg/day ribavirin for 1 year . Patients were followed up for 6 months after the end of treatment . The primary end point was loss of HCV RNA 6 months after the end of treatment . RESULTS Fifty-two patients were r and omized ( treatment , 28 ; placebo , 24 ) . Sixteen patients were withdrawn from the study ; 12 ( 43 % ) were from the treated group ( mainly for anemia [ 7 patients ] ) and 4 ( 17 % ) from the control group . In the treated group , serum HCV RNA was undetectable in 9 patients ( 32 % ) at the end of treatment and 6 ( 21.4 % ) at the end of the follow-up period , whereas no patient in the control group lost HCV RNA at any point ( P = 0.036 at the end of follow-up ) . However , there was no significant histologic improvement . CONCLUSIONS The combination of interferon alfa-2b plus ribavirin induced a sustained virologic response in 21 % of transplant recipients with recurrent hepatitis C. However , 43 % discontinued therapy due to adverse events ( primarily severe anemia ) . Strategies to enable treatment with lower doses of ribavirin need to be explored Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . The aim of the 18 months follow up study was to assess the frequency of anemia during IFN/RBV therapy in patients with chronic hepatitis C ; to manage anemia either with recombinant human erythropoietin (rHuEPO)--epoetin alpha or with RBV dose reduction and to compare the rate of SVR in patients with RBV dose reduction and with administration of epoetin alpha . Study enrolled 61 patients with chronic active hepatitis C aged 33 - 61 years . All patients had HCV genotype 1b . Out of them 41 were male and 20 female . Anemia ( Hb < 10 or > 2 g/dL Hgb drop from baseline ) developed in 41 patients out of 61 ( 67,21 % ) during the therapy . These 41 patients were r and omized into two groups : 21 patients who received 40 000 IU epoetin alpha weekly ( I group ) and 20 patients in whom for managing anemia we used st and ard of care ( SOC ) or RBV dose reductions from 1000/1200 to 800/600 mg ( II group ) . In all 21 patients of the I group the Hb level normalized without reduction of RBV dose . In this group of patients SVR at 6 months after completion of full course of treatment was achieved in 17 ( 66 % ) patients . Improvement of quality of life ( QOL ) was observed in all 21 patients . Out of 20 patients of II group with st and ard of care ( SOC ) 5 patients developed symptomatic anemia with fatigue and dyspnoea ; RBV was stopped temporarily . In 15 patients RBV dose was reduced from 1200 mg to 600 mg for correction of anemia . In this group of patients SVR at 6 months after treatment completion was achieved in 7 ( 25 % ) patients . Lower RBV doses yield a lower treatment response in patients with HCV genotype 1 . In anemic HCV-infected patients on RBV/PEG-IFN therapy , EPO maintains RBV dose and significantly improves anemia and QOL . EPO has the potential to improve adherence rate , which may in turn improve SVR Decompensated liver disease associated with chronic hepatitis C virus ( HCV ) infection is the most common indication for liver transplantation . It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival . The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known . We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b , with or without ribavirin . HCV RNA-positive patients at or near the top of their respective waiting lists were r and omly assigned to one of three treatment regimens until the time of liver transplantation : ( 1 ) group A , interferon alfa-2b , 1 x 10(6 ) U/d ; ( 2 ) group B , interferon alfa-2b , 3 x 10(6 ) U three times weekly ; or ( 3 ) group C , interferon alfa-2b , 1 x 10(6 ) U/d , plus ribavirin , 400 mg twice daily . Less than half the patients screened met entry criteria , with thrombocytopenia and leukopenia the most common reasons for exclusion . Fifteen patients were administered antiviral therapy ; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33 % of patients , whereas 55 % had a decrease in viral titers on therapy . Twenty-three adverse events occurred , including 20 serious adverse events . Thrombocytopenia was the most common adverse event . Two infectious complications occurred ; one of these had a fatal outcome . We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria , adverse events associated with therapy are frequent and often severe in patients with Child 's class B and C cirrhosis Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection . Steroids also have been held responsible for increased infections , posttransplantation diabetes , and recurrent hepatitis after orthotopic liver transplantation ( OLT ) . The purpose of this ongoing prospect i ve r and omized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin ( RATG ) . This is the first report of a prospect i ve r and omized trial in OLT achieving complete absence of steroids . Seventy-one adult patients were prospect ively r and omized to administration of RATG or steroids . Thirty-six patients were r and omized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously ( IV ) beginning during the anhepatic phase . No steroids were administered . Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1 . Thirty-five patients were r and omized to the administration of methylprednisolone , which had been our st and ard immunosuppressive protocol . These patients were administered methylprednisolone , 1,000 mg IV , initiated during the anhepatic phase and followed by steroid taper . Maintenance immunosuppression consisted of tacrolimus and mycophenolate , with or without prednisone . Three patients died in each group , for an overall survival rate of 91 % in each group . One patient in each group required re-OLT , for a graft survival rate of 89 % in each group . Seven patients administered RATG had biopsy-proven rejection ( 20.5 % ) , all of whom were successfully treated by increasing tacrolimus doses . Eleven patients administered steroid had biopsy-proven rejection ( 32 % ) , 7 ( 64 % ) of whom required additional steroids for treatment , whereas 4 patients ( 36 % ) were successfully treated by increasing tacrolimus doses . The incidence of rejection was not statistically significant ; however , there was a significant difference in the incidence of steroid-requiring rejection ( P = .01 ) . The incidence of recurrent hepatitis C was 50 % in RATG patients and 71 % in steroid patients ( P = not significant ) . The incidence and severity of infectious complications were slightly lower in RATG patients , accounted for by a greater incidence of cytomegalovirus ( CMV ) infection in the steroid patients . RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate , decreased incidence of post-OLT diabetes and recurrent hepatitis C , and decreased CMV infection . This prospect i ve r and omized trial gives encouraging support that steroids can be safely eliminated in OLT There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation ( OLT ) . We therefore performed two r and omized , controlled trials -- a prophylaxis trial and a treatment trial -- to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT . The prophylaxis trial enrolled 54 patients within 3 weeks after OLT , and the treatment trial enrolled 67 patients 6 to 60 months after OLT . In each trial , patients were r and omized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter . Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls . However , only 2 treated patients in the prophylaxis trial ( 8 % ) and 3 in the treatment trial ( 12 % ) achieved a sustained virological response . In the prophylaxis trial , 8 patients ( 31 % ) in the peginterferon alfa-2a group and 9 ( 32 % ) in the untreated group were withdrawn prematurely ; whereas in the treatment trial , 10 patients ( 30 % ) in the peginterferon alfa-2a group and 6 ( 19 % ) in the untreated group were withdrawn prematurely . The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis ( 12 % vs. 21 % ; P = .5 ) and treatment ( 12 % vs. 0 % ; P = .1 ) trials . In conclusion , peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting . R and omized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT Hepatitis C virus ( HCV ) infection usually recurs after orthotopic liver transplantation ( OLT ) , and most patients develop graft damage . This study compared the efficacy of interferon alfa ( IFN-alpha ) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft . Thirty OLT recipients with chronic hepatitis C were r and omized to receive either IFN-alpha ( 3 MU three times a week ) or ribavirin ( up to 1.2 g daily ) for 24 weeks . Virological , biochemical , and histological responses to treatment were assessed . Twenty-eight patients completed the treatment regimen , two ribavirin-treated patients being withdrawn because of severe hemolysis . Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin ( 93 % ) and 6 of 14 patients receiving IFN-alpha ( 43 % ; P=.01 ) . Lobular inflammation was reduced in 9/14 ribavirin-treated ( 64 % ) and 3 of 14 IFN-alpha-treated patients ( 21 % ; P=.05 ) , each of whom had a biochemical response . However , the total histological activity index did not improve in either the interferon ( P=.43 ) or the ribavirin ( P=.96 ) group . Posttreatment viremia levels were significantly reduced in IFN-alpha-treated ( P=.05 ) but not in ribavirin-treated ( P=.88 ) patients . Hemolysis occurred in all ribavirin-treated patients , with serum hemoglobin decreasing to < 10 g/dL in 50 % . Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment ( P=.02 and P=.004 , respectively ) . We concluded that in patients with chronic hepatitis C after OLT , IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation , but not the total histological activity index . These findings provide a rationale for combination therapy in the post-OLT setting , although patients must be carefully monitored for hemolysis Background . Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients . St and ard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients . Methods . Twelve patients , at least 7 months posttransplant , with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were r and omized to interferon-&agr;2a , 3 mU daily for 12 months ( n=8 ) or no treatment ( n=4 ) . The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level , quasispecies evolution , and liver histology were studied . Results . Treated patients had an improvement in histological activity index at the end of therapy relative to controls ( median reduction of 2 versus median increase of 1.5 ) ( P = 0.04 ) . Four treated patients had a virological response ( all bDNA negative , one qualitative polymerase chain reaction negative ) compared with none of the untreated patients . Only two of six treated patients tested had evidence of quasispecies diversification on therapy . Seven of eight patients in the treatment group required dose reduction for fatigue and /or depression . They tolerated 1.5 mU of interferon-&agr;2a daily . Two treated patients developed graft dysfunction , one of who had histological evidence of rejection and subsequent graft loss . Conclusions . Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases . These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant BACKGROUND / AIMS We performed a r and omized trial on pegylated interferon alfa-2a ( Peg-IFNalpha ) monotherapy vs Peg-IFNalpha and ribavirin in non-cirrhotic liver transplant recipients with recurrent hepatitis C. METHODS Forty-two patients transplanted for HCV-related cirrhosis 12 - 96 months earlier were r and omized to Peg-IFNalpha monotherapy ( 180 microg weekly ) or Peg-IFNalpha and ribavirin , up to the maximum tolerated dose , for 48 weeks . RESULTS Early virological response ( EVR , i.e. , HCV-RNA2 log drop at week 12 ) occurred in 76 % of the monotherapy and 71 % of the combination groups , respectively ( intention-to treat ) . Sustained virological response ( SVR ) occurred in 8 ( 38 % ) and 7 ( 33 % ) patients , respectively . EVR had a positive predictive value for SVR of 50 % and 47 % , respectively , and a 100 % negative predictive value in both groups . Six drop-outs occurred in the monotherapy ( including 3 rejections ) and 7 in the combination groups ( including one rejection ) . Peg-INFalpha dose was reduced in 7 and 8 patients , respectively . The average daily dose of ribavirin was 435 mg/day . CONCLUSIONS Peg-IFNalpha-2a , with or without ribavirin , induces SVR in one-third of transplant recipients with recurrent hepatitis C. Treatment cessation is indicated in patients without EVR . The low SVR rate is mainly due to inability to sustain full doses of antivirals and lack of the booster effect of ribavirin BACKGROUND & AIMS Combination therapy with interferon alpha ( IFN-alpha ) and ribavirin ( RBV ) or pegylated IFN-alpha (PEG-IFN-alpha)/RBV for chronic hepatitis C virus ( HCV ) infection often causes anemia , prompting RBV dose reduction/discontinuation . This study assessed whether epoetin alfa could maintain RBV dose , improve quality of life ( QOL ) , and increase hemoglobin ( Hb ) in anemic HCV-infected patients . METHODS HCV-infected patients ( n = 185 ) on combination therapy who developed anemia ( Hb < or = 12 g/dL ) were r and omized into a U. S. multicenter , placebo-controlled , clinical trial of epoetin alfa , 40,000 U subcutaneously , once weekly vs. matching placebo . The study design used an 8-week , double-blind phase ( DBP ) followed by an 8-week , open-label phase ( OLP ) , in which placebo patients were crossed over to epoetin alfa . RESULTS At the end of the DBP , RBV doses were maintained in 88 % of patients receiving epoetin alfa vs. 60 % of patients receiving placebo ( P < 0.001 ) . Mean QOL scores at the end of the DBP improved significantly on all domains of the Linear Analog Scale Assessment ( LASA ) and on 7 of the 8 domains of the Short Form-36 , version 2 ( SF-36v2 ) . Mean Hb increased by 2.2 + /- 1.3 g/dL ( epoetin alfa ) and by 0.1 + /- 1.0 g/dL ( placebo ) in the DBP ( P < 0.001 ) . Similar results were demonstrated in patients who switched from placebo to epoetin alfa in the OLP . Epoetin alfa was well tolerated ; the most common adverse effects were headache and nausea . CONCLUSIONS Epoetin alfa maintained RBV dose and improved QOL and Hb in anemic HCV-infected patients receiving combination therapy To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results |
2,155 | 25,799,928 | Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins , these findings could be attributable to reverse causation .
RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia . | Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive .
Here , our objective was to systematic ally review , synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition , so as to assess the current state of knowledge , identify gaps in our underst and ing , and make recommendations for future research . | Objectives To estimate survival after a diagnosis of dementia in primary care , compared with people without dementia , and to determine incidence of dementia . Design Cohort study using data from The Health Improvement Network ( THIN ) , a primary care data base . Setting 353 general practice s in the United Kingdom providing data to THIN . Participants All adults aged 60 years or over with a first ever code for dementia from 1990 to 2007 ( n=22 529 ) ; r and om sample of five participants without dementia for every participant with dementia matched on practice and time period ( n=112 645 ) . Main outcome measures Median survival by age and sex ; mortality rates ; incidence of dementia by age , sex , and deprivation . Results The median survival of people with dementia diagnosed at age 60 - 69 was 6.7 ( interquartile range 3.1 - 10.8 ) years , falling to 1.9 ( 0.7 - 3.6 ) years for those diagnosed at age 90 or over . Adjusted mortality rates were highest in the first year after diagnosis ( relative risk 3.68 , 95 % confidence interval 3.44 to 3.94 ) . This dropped to 2.49 ( 2.29 to 2.71 ) in the second year . The incidence of recorded dementia remained stable over time ( 3 - 4/1000 person years at risk ) . The incidence was higher in women and in younger age groups ( 60 - 79 years ) living in deprived areas . Conclusions Median survival was much lower than in screened population s. These clinical ly relevant estimates can assist patients and carers , clinicians , and policy makers when planning support for this population . The high risk of death in the first year after diagnosis may reflect diagnoses made at times of crisis or late in the disease trajectory . Late recording of diagnoses of dementia in primary care may result in missed opportunities for potential early interventions This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Background Globally , dengue infections constitute a significant public health burden . In recent decades , Malaysia has become a dengue hyper-endemic country with the co-circulation of the four dengue virus serotypes . The cyclical dominance of sub-types contributes to a pattern of major outbreaks . The consequences can be observed in the rising incidence of reported dengue cases and dengue related deaths . Underst and ing the complex interaction of the dengue virus , its human hosts and the mosquito vectors at the community level may help develop strategies for addressing the problem . Methods A prospect i ve cohort study will be conducted in Segamat district of Johor State in Peninsular Malaysia . Research ers received approval from the Malaysian Medical Research Ethics Committee and Monash University Human Research Ethics Committee . The study will be conducted at a Malaysian based health and demographic surveillance site over a 1 year period in three different setting s ( urban , semi-urban and rural ) . The study will recruit healthy adults ( male and female ) aged 18 years and over , from three ethnic groups ( Malay , Chinese and Indian ) . The sample size calculated using the Fleiss method with continuity correction is 333 . Sero-surveillance of participants will be undertaken to identify asymptomatic , otherwise healthy cases ; cases with dengue fever who are managed as out- patients ; and cases with dengue fever admitted to a hospital . A genetic analysis of the participants will be undertaken to determine whether there is a relationship between genetic predisposition and disease severity . A detailed medical history , past history of dengue infection , vaccination history against other flaviviruses such as Japanese encephalitis and Yellow fever , and the family history of dengue infection will also be collected . In addition , a mosquito surveillance will be carried out simultaneously in recruitment areas to determine the molecular taxonomy of circulating vectors . Discussion The research findings will estimate the burden of asymptomatic and symptomatic dengue at the community level . It will also examine the relationship between virus serotypes and host genotypes , and the association of the clinical manifestation of the early phase with the entire course of illness BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people Sleep disturbances and decrements of daytime performance have been attributed to HMG-CoA reductase inhibitors . As a rule , lipophilic compounds more readily cross the blood-brain barrier and are more likely to affect central nervous system function . The authors compared the effects of lovastatin ( 40 mg ) , a lipophilic compound , to pravastatin ( 40 mg ) , a hydrophilic compound , in a 6-week , double-blind , r and omized , placebo-controlled , three-way Latin square design , cross-over study on 22 men with hypercholesterolemia . Patients had LDL cholesterol of more than 165 mg/dL and triglyceride of less than 350 mg/dL after 6 weeks of a low-fat ( < 30 % ) , low-cholesterol ( < 300 mg/day ) diet . Compared with placebo , there were no significant effects of lovastatin or pravastatin on the following subjective and polysomnographic sleep measures : changes in total sleep time , time in each sleep stage , sleep efficiency , sleep latency , REM density , REM activity , and number of arousals . Similarly , there were no effects of the two drugs on measures of cognitive performance . A significant increase in the duration of nocturnal tumescence ( NPT ) was observed after 2 weeks of treatment with both study drugs . This effect was not significant after 6 weeks of treatment . Both lovastatin and pravastatin caused significant ( P < .05 compared with placebo ) decreases in total cholesterol ( by 20.9 and 20.6 % , respectively ) , LDL cholesterol ( by 27.8 and 29.9 % ) , and triglycerides ( by 13.6 and 3.7 % ) . Subjects ' HDL increased by 2.3 % with lovastatin ( NS ) and by 3.1 % with pravastatin ( P < .05 ) . Lipoprotein(a ) increased by 20.5 % with lovastatin and by 1.1 % with pravastatin ; these changes were not significantly different from placebo . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this prospect i ve cohort study was to evaluate the effects of lipid lowering agent ( LLA ) intake on cognitive function in 6,830 community-dwelling elderly persons . Cognitive performance ( global cognitive functioning , visual memory , verbal fluency , psychomotor speed , and executive function ) , clinical diagnosis of dementia , and fibrate and statin use , were evaluated at baseline , and 2 , 4 , and 7 year follow-up . Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics , mental and physical health including vascular risk factors , and genetic vulnerability ( apolipoprotein E and cholesteryl ester transfer protein ) . For women but not men , fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only ( HR = 1.29 , 95 % CI = 1.09 - 1.54 , p = 0.004 ) , and did not increase risk for incident dementia . This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate ( HR = 1.39 , 95 % CI = 1.08 - 1.79 , p = 0.01 ) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment . For both genders , no significant associations were found between statins ( irrespective of their lipophilicity ) and either cognitive decline or dementia incidence . This prospect i ve study , adjusting for multiple confounders , found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia , but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory Because cerebrospinal fl(CSF ) abnormalities in presymptomatic subjects with PSEN1 ( presenilin 1 ) mutations may be observed 4 to 12 years prior to the estimated age at onset , it is possible to test putative therapies on the CSF analytes that correlate with neurodegeneration during this presymptomatic window of clinical opportunity . It is also possible to test the same therapy on a comparison group with increased risk status conferred by both hyperlipidemia and heterozygosity for apolipoprotein Ee4 . To our knowledge , the only putative therapy thus far tested in such a common design has been statin therapy . The results of these tests show increases in soluble amyloid precursor protein (sAPP)α correlating with statininduced decreases in serum cholesterol levels in the non-PSEN1 subjects . This result could be one functional correlate for part of the substantial risk reduction for late onset Alzheimer ’s disease recently reported in the Rotterdam study , a large , long-term prospect i ve statin trial . Statin therapy signifi cantly decreased both sAPPα and sAPPβ in presymptomatic PSEN1 subjects . Initially , elevated phospho-tau levels in PSEN1 subjects did not further increase during the 2 to 3 years of statin therapy , possibly indicative of a prophylactic eff ect . These results suggest that large and longer term trials of statin therapy correlating changes in CSF biomarker levels with clinical course may be warranted in both presymptomatic PSEN1 and non-PSEN1 subjects Background : Previously reported associations between statin use and incident dementia or cognitive decline have been inconsistent . We report the results from a 3-year prospect i ve study on the association of statin use on cognitive decline and incident dementia in elderly African Americans . Methods : A community-based cohort of 1,146 African Americans aged 70 and older living in Indianapolis , Indiana , was evaluated in 2001 and 2004 . The instrument used for cognitive assessment was the Community Screening Interview for Dementia ( CSI-D ) . Cognitive decline was defined as CSI-D scores measured at 2001 minus scores at 2004 . Measurements of low-density lipoprotein cholesterol ( LDL-C ) and C-reactive protein ( CRP ) were obtained from baseline blood sample s. Results : Adjusting for age at baseline , gender , education , and the possession of ApoE ε4 allele , baseline statin use was associated with less cognitive decline ( p = 0.0177 ) . There were no significant interactions of statin use when LDL-C and CRP were included . Logistic regression with the four independent variables showed that statin use may be associated with a reduction in incident dementia ( OR = 0.32 ; p = 0.0673 ) . Association with cognitive decline was less clear when investigating statin use over time . Significance remained only for those who discontinued prior to follow-up compared to continuous users or users who started after baseline . Conclusions : The relationship between statin use and cognitive decline is complex and subjected to unknown confounders . This effect may not be associated with the cholesterol lowering or anti-inflammatory action of statins . GLOSSARY : AD = Alzheimer disease ; ANCOVA = analysis of covariance ; BMI = body mass index ; CAMDEX = Cambridge Examination for Mental Disorders of the Elderly informant interview ; CERAD = Consortium to Establish a Registry for Alzheimer ’s Disease ; CHIF = Clinician Home-based Interview to assess Function ; CRP = C-reactive protein ; CSI-D = Community Screening Instrument for Dementia ; HDL = high-density lipoprotein ; HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A ; LDL-C = low-density lipoprotein cholesterol ; LLAs = lipid-lowering agents ; NSAIDs = nonsteroidal anti-inflammatory drugs BACKGROUND Prior reports suggest reduced occurrence of dementia and Alzheimer disease ( AD ) in statin users , but , to our knowledge , no prospect i ve studies relate statin use and dementia incidence . OBJECTIVE To examine the association of statin use with both prevalence and incidence of dementia and AD . DESIGN Cross-sectional studies of prevalence and incidence and a prospect i ve study of incidence of dementia and AD among 5092 elderly residents ( aged 65 years or older ) of a single county . Participants were assessed at home in 1995 - 1997 and again in 1998 - 2000 . A detailed visual inventory of medicines , including statins and other lipid-lowering agents , was collected at both assessment s. MAIN OUTCOME MEASURES Diagnosis of dementia and of AD . RESULTS From 4895 participants with data sufficient to determine cognitive status , we identified 355 cases of prevalent dementia ( 200 with AD ) at initial assessment . Statin use was inversely associated with prevalence of dementia ( adjusted odds ratio , 0.44 ; 95 % confidence interval , 0.17 - 0.94 ) . Three years later , we identified 185 cases of incident dementia ( 104 with AD ) among 3308 survivors at risk . Statin use at baseline did not predict incidence of dementia or AD ( adjusted hazard ratio for dementia , 1.19 ; 95 % confidence interval , 0.53 - 2.34 ; adjusted hazard ratio for AD , 1.19 ; 95 % confidence interval , 0.35 - 2.96 ) , nor did statin use at follow-up ( adjusted odds ratio for dementia , 1.04 ; 95 % confidence interval , 0.56 - 1.81 ; adjusted odds ratio for AD , 0.85 ; 95 % confidence interval , 0.32 - 1.88 ) . CONCLUSIONS Although statin use might be less frequent in those with prevalent dementia , we found no association between statin use and subsequent onset of dementia or AD . Further research is warranted before costly dementia prevention trials with statins are undertaken Background : Cross-sectional reports suggest that statin users are less likely to have Alzheimer disease ( AD ) . Prospect i ve studies have provided inconsistent evidence . Moreover , it is unclear whether the association differs for lipohilic statins , those that could more easily pass the blood – brain barrier and hydrophilic statins . Objectives : To prospect ively evaluate whether use of statins is associated with the risk of AD , and to determine whether associations differ for lipophilic and hydrophilic statins . Method : 6992 participants of the prospect i ve , population -based Rotterdam Study were followed , from baseline ( 1990–1993 ) until January 2005 for incident AD . Data on all filled prescriptions came from pharmacy records . For each date on which each event occurred , cholesterol-lowering drug use for the person who experienced the event and all remaining persons in the cohort was categorised as “ any ” or “ never ” use . A distinction was made between statin , lipophilic and hydrophilic statins , and non-statin cholesterol-lowering drugs . Data were analysed with the Cox regression analysis , adjusting for sex , age and potential confounders . Results : During follow-up ( mean 9 years ) , 582 persons developed AD . Compared with never use of cholesterol-lowering drugs , statin use was associated with a decreased risk of AD ( HR 0.57 ; 95 % CI 0.37 to 0.90 ) , but non-statin cholesterol-lowering drug use was not ( HR 1.05 ; 95 % CI 0.45 to 2.44 ) . HRs were equal for lipophilic ( HR 0.54 ; 95 % CI 0.32 to 0.89 ) and hydrophilic statins ( HR 0.54 ; 95 % CI 0.26 to 1.11 ) . Conclusion : In the general population , the use of statins , but not of non-statin cholesterol-lowering drugs , was associated with a lower risk of AD compared with never use of cholesterol-lowering drugs . The protective effect was independent of the lipophilicity of statins PURPOSE Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function , mood , and behavior , but few clinical trials have studied these effects . SUBJECTS AND METHODS In this double-blind investigation , 209 generally healthy adults with a serum low-density-lipoprotein ( LDL ) cholesterol level of 160 mg/dL or higher were r and omly assigned to 6-month treatment with lovastatin ( 20 mg ) or placebo . Assessment s of neuropsychological performance , depression , hostility , and quality of life were conducted at baseline and at the end of the treatment period . Summary effect sizes were estimated as z scores on a st and ard deviation ( SD ) scale . RESULTS Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains , consistent with the effects of practice on test performance ( all P < 0.04 ) , whereas those treated with lovastatin improved only on tests of memory recall ( P = 0.03 ) . Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small , but statistically significant , differences for tests of attention ( z score = 0.18 ; 95 % confidence interval ( CI ) , 0.06 to 0.31 ; P = 0.005 ) and psychomotor speed ( z score = 0.17 ; 95 % CI , 0.05 to 0.28 ; P = 0 . 004 ) that were consistent with greater improvement in the placebo group . Psychological well-being , as measured several ways , was not affected by lovastatin . CONCLUSION Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function . Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed , the clinical importance of which is uncertain AIMS To assess the effect of statins on a range of health outcomes . METHODS We undertook a population -based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins . We vali date d our design by comparing our results for vascular outcomes with the effects established in large r and omized trials . The study was based on the United Kingdom Health Improvement Network data base that includes the computerized medical records of over four and a half million patients . RESULTS People who initiated treatment with a statin ( n = 129,288 ) were compared with a matched sample of 600,241 people who did not initiate treatment , with a median follow-up period of 4.4 years . Statin use was not associated with an effect on a wide range of outcomes , including infections , fractures , venous thromboembolism , gastrointestinal haemorrhage , or on specific eye , neurological or autoimmune diseases . A protective effect against dementia was observed ( hazard ratio 0.80 , 99 % confidence interval 0.68 , 0.95 ) . There was no effect on the risk of cancer even after > or = 8 years of follow-up . The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large r and omized trials , suggesting bias and confounding had been well controlled for . CONCLUSIONS We found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease Objective To quantify the unintended effects of statins according to type , dose , and duration of use . Design Prospect i ve open cohort study using routinely collected data . Setting 368 general practice s in Engl and and Wales supplying data to the Q Research data base . Participants 2 004 692 patients aged 30 - 84 years of whom 225 922 ( 10.7 % ) were new users of statins : 159 790 ( 70.7 % ) were prescribed simvastatin , 50 328 ( 22.3 % ) atorvastatin , 8103 ( 3.6 % ) pravastatin , 4497 ( 1.9 % ) rosuvastatin , and 3204 ( 1.4 % ) fluvastatin . Methods Cox proportional hazards models were used to estimate effects of statin type , dose , and duration of use . The number needed to treat ( NNT ) or number needed to harm ( NNH ) was calculated and numbers of additional or fewer cases estimated for 10 000 treated patients . Main outcome measure First recorded occurrence of cardiovascular disease , moderate or serious myopathic events , moderate or serious liver dysfunction , acute renal failure , venous thromboembolism , Parkinson ’s disease , dementia , rheumatoid arthritis , cataract , osteoporotic fracture , gastric cancer , oesophageal cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Results Individual statins were not significantly associated with risk of Parkinson ’s disease , rheumatoid arthritis , venous thromboembolism , dementia , osteoporotic fracture , gastric cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction , acute renal failure , moderate or serious myopathy , and cataract . Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin . A dose-response effect was apparent for acute renal failure and liver dysfunction . All increased risks persisted during treatment and were highest in the first year . After stopping treatment the risk of cataract returned to normal within a year in men and women . Risk of oesophageal cancer returned to normal within a year in women and within 1 - 3 years in men . Risk of acute renal failure returned to normal within 1 - 3 years in men and women , and liver dysfunction within 1 - 3 years in women and from three years in men . Based on the 20 % threshold for cardiovascular risk , for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 ( 95 % confidence interval 27 to 64 ) and for oesophageal cancer was 1266 ( 850 to 3460 ) and for men the respective values were 33 ( 24 to 57 ) and 1082 ( 711 to 2807 ) . In women the NNH for an additional case of acute renal failure over five years was 434 ( 284 to 783 ) , of moderate or severe myopathy was 259 ( 186 to 375 ) , of moderate or severe liver dysfunction was 136 ( 109 to 175 ) , and of cataract was 33 ( 28 to 38 ) . Overall , the NNHs and NNTs for men were similar to those for women , except for myopathy where the NNH was 91 ( 74 to 112 ) . Conclusions Cl aims of unintended benefits of statins , except for oesophageal cancer , remain unsubstantiated , although potential adverse effects at population level were confirmed and quantified . Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely BACKGROUND Statins reduce amyloid-beta ( Abeta ) levels in the brain and cerebrospinal fluid ( CSF ) in animals and may thereby favorably alter the pathobiology of AD . It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD . METHODS In a 4-month r and omized , double-blind , controlled study , we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Abeta42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD . RESULTS Compared to placebo , individuals r and omized to simvastatin for 4 months had similar changes in CSF Abeta42 ( p=0.344 ) and total tau levels ( p=0.226 ) , yet greater improvements in some measures of verbal fluency ( p=0.024 ) and working memory ( p=0.015 ) . APOE4 genotype , gender , and vascular risk factors were associated with CSF biomarker levels , but did not modify treatment effects . CONCLUSION In asymptomatic middle-aged adults at increased risk for AD , simvastatin use improved selected measures of cognitive function without significantly changing CSF Abeta42 or total tau levels . Further studies are needed to clarify the impact of higher dose and /or longer duration statin therapy on not only Abeta metabolism , but also other pre clinical processes related to the development of AD Observational studies have given conflicting results about the effect of statins in preventing dementia and cognitive decline . Moreover , observational studies are subject to prescription bias , making it hard to draw definite conclusions from them . R and omized controlled trials are therefore the preferred study design to investigate the association between statins and cognition . Here we present detailed cognitive outcomes from the r and omized placebo-controlled PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) . Cognitive function was assessed repeatedly in all 5,804 PROSPER participants at six different time points during the study using four neuropsychological performance tests . After a mean follow-up period of 42 months , no difference in cognitive decline at any of the cognitive domains was found in subjects treated with pravastatin compared to placebo ( all p > 0.05 ) . Pravastatin treatment in old age did not affect cognitive decline during a 3 year follow-up period . Employing statin therapy in the elderly in an attempt to prevent cognitive decline therefore seems to be futile BACKGROUND Lipid-lowering medications ( LLMs ) and especially statin drugs can delay cognitive decline and dementia onset in individuals with and without mild cognitive impairment ( MCI ) at baseline . METHODS A longitudinal , observational study was conducted of 3069 cognitively healthy elderly patients ( ≥75 years of age ) who were enrolled in the Ginkgo Evaluation of Memory Study . The primary outcome measure was the time to adjudicated all-cause dementia and Alzheimer dementia ( AD ) . The secondary outcome measure was the change in global cognitive function over time measured by scores from the Modified Mini-Mental State Exam ( 3MSE ) and the cognitive subscale of the AD Assessment Scale ( ADAS-Cog ) . RESULTS Among participants without MCI at baseline , the current use of statins was consistently associated with a reduced risk of all-cause dementia ( hazard ratio [ HR ] , 0.79 ; 95 % confidence interval [ 95 % CI ] , 0.65 - 0.96 ; P = .021 ) and AD ( HR , 0.57 ; 95 % CI , 0.39 - 0.85 ; P = .005 ) . In participants who initiated statin therapy , lipophilic statins tended to reduce dementia risk more than nonlipophilic agents . In contrast , there was no significant association between LLM use ( including statins ) , dementia onset , or cognitive decline in individuals with baseline MCI . However , in individuals without MCI at baseline , there was a trend for a neuroprotective effect of statins on cognitive decline . CONCLUSIONS Statins may slow the rate of cognitive decline and delay the onset of AD and all-cause dementia in cognitively healthy elderly individuals , whereas individuals with MCI may not have comparable cognitive protection from these agents . However , the results from this observational study need to be interpreted with caution and will require confirmation by r and omized clinical trials stratifying treatment groups based on MCI status at baseline The HMG‐CoA reductase inhibitors lovastatin and pravastatin have both proven to be effective and well tolerated in the treatment of hypercholesterolemia . To evaluate whether lovastatin or pravastatin might affect daytime cognitive function , a double‐blind , placebo‐controlled , two‐period , incomplete block , crossover study was performed in 36 patients ( 24 per treatment ) with primary hypercholesterolemia . Patients received placebo , Iovastatin ( 40 mg ) , or pravastatin ( 40 mg ) for 4 weeks . Following a 1‐week washout period , patients were crossed over to either lovastatin , pravastatin , or placebo for an additional 4 weeks . Mental performance tests ( digit symbol substitution , choice reaction time , auditory vigilance , selective reminding word recall , finger tapping ) , visual analogue rating scales , and the Profile of Mood States were administered before test drug administration and after 2 and 4 weeks of each treatment . After 4 weeks , no statistically significant differences between treatments in changes from baseline were observed on any parameter with the exception of digit symbol substitution , for which lovastatin and pravastatin were both significantly better than placebo but did not differ from each other . Low‐density lipoprotein cholesterol was reduced 38 % by lovastatin and 30 % by pravastatin . In summary , neither of these chemically distinct HMG‐CoA reductase inhibitors impaired daytime cognitive performance after 4 weeks of treatment in patients with primary hypercholesterolemia 1 . The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind , placebo-controlled , r and omised crossover study . 2 . Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin , 40 mg day-1 pravastatin or placebo for 4 weeks , separated by a 4 - 6 week washout phase . 3 . CNS measures included EEG evoked potentials , power spectral analysis , Leeds Sleep Question naire , Hospital Anxiety Depression ( HAD ) Scale , and Digit Symbol Substitution Test ( DSST ) ; biochemical measures included plasma cholesterol , liver enzymes ( gamma-GT , AST , ALT ) and creatine kinase . 4 . Mean cholesterol concentrations with both drugs were significantly lower than with placebo , and the cholesterol-lowering effect was greater with simvastatin . There were no significant differences between treatment in EEG evoked potentials , HAD Scale , or DSST scores . On the sleep measure , subjects reported significantly greater difficulty in getting to sleep while on simvastatin than on pravastatin , but neither score differed from placebo . No significant correlations were observed between sleep ratings and either plasma cholesterol concentrations or EEG evoked potentials . 5 . The study showed that , while both drugs reduced plasma cholesterol concentrations , neither exerted significant effects , compared with placebo , on EEG evoked potentials , mood , sleep , or cognitive performance after 4 weeks of chronic administration in healthy volunteers Pravastatin and lovastatin , two HMG‐CoA reductase inhibitors with similar cholesterol‐lowering effects , differ in their lipid solubility . The hydrophilic characteristics of pravastatin may explain why the drug has not been detected in cerebrospinal fluid . On the other h and , lovastatin , a lipophilic compound , has been detected in the cerebrospinal fluid . Previous reports have suggested that lovastatin administration may be associated with insomnia , which reflects an action in the central nervous system . The effects of the two drugs on nocturnal sleep and daytime performance in young , healthy men have been assessed in r and omized , double‐blind , placebo‐controlled studies . Computer‐based performance tests were administered on two consecutive days before drug administration and at the end of a 3‐week active drug or placebo treatment period . Results from both sites were combined for analysis . Neither pravastatin nor lovastatin significantly affected nocturnal sleep or daytime sleepiness in this study population , but lovastatin significantly affected daytime performance . In subjects treated with lovastatin , the results showed that two measures of performance , divided attention ( p<0.05 ) and vigilance ( p<0.01 ) , worsened significantly from baseline as did global performance ( p<0.01 ) . Performance was not affected in the pravastatin and placebo groups . These results provide preliminary evidence of an adverse effect of lovastatin on daytime performance According to the amyloid cascade hypothesis , sporadic Alzheimer ’s disease ( AD ) is caused by the production and aggregation of β-amyloid ( Aβ ) , and the production of Aβ has recently been linked to the metabolism of cholesterol . We have previously published clinical studies where the effect of statin treatment on Aβ production has been investigated . No effect on Aβ was found , which is in disagreement with cell and animal studies . In the present study we investigated the effect of statin treatment on a disease-specific pattern consisting of a C-terminally-truncated quintet of Aβ peptides . Nineteen patients with AD were treated with simvastatin for 12 months and the quintet of Aβ peptides were analysed in cerebrospinal fluid before and after treatment . Also included was a group of 15 untreated patients with AD . We found that the Aβ peptide pattern at baseline was in agreement with earlier findings ; however , we did not find any change in the Aβ peptide pattern after statin treatment . We suggest that clinical studies with extended treatment periods are performed where higher dosages of statins are used . We also believe that the pleiotropic effects of statins should be investigated further in order to eluci date the connection between Alzheimer ’s disease and statin treatment OBJECTIVES To determine the association between prescribed medication and life long changes in cognitive ability . DESIGN Retrospective cohort study . SETTING Community residents of a largely urban region of South East Scotl and . PARTICIPANTS Four hundred and seventy-eight survivors of the 1932 Scottish Mental Health Survey ( n=87,498 ) without dementia . MEASUREMENTS The Moray House Test ( MHT ) of intelligence administered at age 11 and age 80 years . Hospital Anxiety and Depression Scale ( HADS ) score , history of disease and current prescribed medications age 80 years . RESULTS After adjusting for sex , neuroactive drugs had a detrimental effect on life long cognitive change age ( F=12.2 , p=0.001 , partial eta-squared=0.026 ) , statins a beneficial effect ( F=5.78 , p=0.017 , partial eta-squared=0.013 ) and polypharmacy a detrimental effect ( F=6.46 , p=0.011 , partial eta-squared=0.014 ) . In the optimal model estimated marginal means revealed : a relative improvement for statin users , IQ age 11=93.2 ( 95 % CI 87.9 - 98.4 ) and age 80=100.6 ( 95 % CI 95.3 - 105.9 ) ; compared with non-users , IQ age 11=100.9 ( 95 % CI 99.4 - 102.3 ) and age 80=100.0 ( 95 % CI 98.6 - 101.5 ) . CONCLUSIONS Clinical ly , the degree to which drugs impair cognition in relatively fit , older people may not be apparent . However , in population terms , medication use , particularly polypharmacy , is important . Statins , used as currently indicated for cardiovascular disease , appear promising in ameliorating cognitive decline in older people . However , firm recommendation of their use should await the outcome of ongoing r and omised clinical trials BACKGROUND As evidence has accumulated for the role of HMG-CoA reductase inhibitors in the primary prevention of coronary artery disease , younger individuals with no other co-morbid conditions will be increasingly exposed to these agents . Some HMG-CoA reductase inhibitors have been reported to cause impairment of daytime cognitive processes that have the potential to directly impact the ability of pilots and other aircrew to perform . These studies suggested that there might be cognitive effects of these medications that would argue against their routine use in population s whose activities required high , sustained levels of cognitive performance . The objective of this study is to establish the effects of pravastatin and lovastatin on aircrew daytime cognitive function using tests that are correlated with actual cockpit tasks and inflight performance . METHODS Military aircrew with hypercholesterolemia were enrolled in the study and assigned to lovastatin , pravastatin or placebo groups . Baseline cognitive and vigilance testing was performed with computerized test instruments . Following a 4-wk treatment period , subjects were retested on both cognitive and vigilance tasks . RESULTS Laboratory studies confirmed that both medications were effective in lowering cholesterol . No major treatment-related side effects were encountered . Cognitive performance was not affected by either active treatment , and was not different from that of the placebo group . CONCLUSIONS The tested medications did not have significant effects on performance as measured by two computerized performance tests . The data suggest that neither medication has significant effects on flight-related performance The effects of equi-efficacious doses of the cholesterol-lowering drugs simvastatin ( 20 mg day-1 ) and pravastatin ( 40 mg day-1 ) on tests of cognitive function were investigated in a double-blind , placebo-controlled , 2-period ( 4 weeks per period ) , incomplete block , crossover study of 36 patients ( 24 per treatment ) with hypercholesterolaemia . After 4 weeks neither of the active treatments differed significantly from placebo on any cognitive measure STUDY OBJECTIVE To examine the effect of atorvastatin on cognitive function by testing two hypotheses : that atorvastatin 10 mg/day would impair cognitive function , and that other biochemical and demographic measures would better predict cognitive performance than atorvastatin alone . DESIGN R and omized , double-blind , placebo-controlled study . SETTING Two primary acute care setting s in the north and northwest of Tasmania , Australia . PATIENTS Fifty-seven patients from the Lipid Lowering and Onset of Renal Disease ( LORD ) trial . INTERVENTION Participants were r and omly assigned to receive either atorvastatin 10 mg/day or matching placebo . Cognitive testing was performed in two sessions occurring 12 weeks apart and involved three repeated measures of attention and concentration . MEASUREMENTS AND MAIN RESULTS Performance was measured using three st and ard neuropsychological tests : Digit Symbol Coding subtest , Trail Making Test , and Stroop Color-Word Reading Test . Patients received atorvastatin for a mean of 72.93 weeks and placebo for a mean of 68.85 weeks . Repeated- measures multivariate analysis of variance failed to identify any significant differences between the two groups on any of the three cognitive measures . Multiple regression analyses identified no single factor or combination of plasma cholesterol levels , renal function , liver function , or age that predicted cognitive performance in either the atorvastatin or placebo group on the three measures at either testing session . CONCLUSION Atorvastatin 10 mg/day did not produce decrements to cognitive performance . In addition , biochemical and demographic measures and the receipt of atorvastatin versus placebo did not individually or in combination predict cognitive performance on measures of attention and concentration PURPOSE In our initial study of the potential effects of cholesterol-lowering interventions on cognitive functioning , treatment with lovastatin as compared with placebo caused performance decrements on several neuropsychological tests , whereas scores on other tests were unaffected . The current study was design ed to confirm and extend those findings . METHODS The study comprised 308 hypercholesterolemic adults between 35 and 70 years of age . Employing a r and omized double-blind design , we assigned participants to daily treatment with placebo , 10 mg of simvastatin , or 40 mg of simvastatin for 6 months . A neuropsychological test battery was administered to assess cognitive functioning at baseline and at the end of the treatment period . RESULTS A total of 283 subjects completed the study : 94 subjects on placebo , 96 taking 10 mg of simvastatin , and 93 taking 40 mg of simvastatin . Compared with placebo , decremental effects of simvastatin treatment were found on tests previously observed to be sensitive to statins ( P = 0.008 ; difference in summary z scores = 0.18 ; 95 % confidence interval [ CI ] : 0.07 to 0.29 ) and on tests not previously administered ( P = 0.04 ; difference in summary z scores = 0.17 ; 95 % CI : 0.05 to 0.29 ) , but not on tests previously observed to be insensitive to statins ( P = 0.84 ; difference in summary z scores = 0.02 ; 95 % CI : -0.07 to 0.10 ) . For the three tests specifically affected by simvastatin , effects on cognitive performance were small , manifest only as failure to improve during the 6 months of treatment ( compared with placebo ) , and were confounded by baseline differences on one test . CONCLUSION This study provides partial support for minor decrements in cognitive functioning with statins . Whether such effects have any long-term sequelae or occur with other cholesterol-lowering interventions is not known Background : Studies of hypertension and cognition variously report adverse , null , and protective associations . We evaluated evidence supporting three potential explanations for this variation : an effect of hypertension duration , an effect of age at hypertension initiation , and selection bias due to dependent censoring . Methods : The Normative Aging Study is a prospect i ve cohort study of men in the greater Boston area . Participants completed study visits , including hypertension assessment , every 3–5 years starting in 1961 . Seven hundred fifty-eight of 1,284 men eligible at baseline completed cognitive assessment between 1992 and 2005 ; we used the mean age-adjusted cognitive test Z score from their first assessment to quantify cognition . We estimated how becoming hypertensive and increasing age at onset and duration since hypertension initiation affect cognition . We used inverse probability of censoring weights to reduce and quantify selection bias . Results : A history of hypertension diagnosis predicted lower cognition . Increasing duration since hypertension initiation predicted lower mean cognitive Z score ( −0.02 st and ard units per year increase [ 95 % confidence interval= −0.04 to −0.001 ] ) , independent of age at onset . Comparing participants with and without hypertension , we observed noteworthy differences in mean cognitive score only for those with a long duration since hypertension initiation , regardless of age at onset . Age at onset was not associated with cognition independent of duration . Analyses design ed to quantify selection bias suggested upward bias . Conclusions : Previous findings of null or protective associations between hypertension and cognition likely reflect the study of persons with short duration since hypertension initiation . Selection bias may also contribute to cross- study heterogeneity Statins have been reported to reduce the risk and be of benefit in the treatment of Alzheimer 's disease ( AD ) . Individuals enrolling in the r and omized controlled trial testing two anti-inflammatory agents for primary prevention of AD ( Alzheimer 's Disease Anti-inflammatory Prevention Trial ; ADAPT ) were allowed the elective use of statins . Our objective was to assess whether statin use is associated with reduced risk of incident AD among ADAPT participants . In primary ADAPT study , participants were assessed annually for cholesterol levels and cognitive status . If impairment in cognition was noted , a dementia evaluation was performed . Onset of mild cognitive impairment ( MCI ) or AD was taken as the date of this evaluation . Time-to-onset was analyzed in six-month intervals following enrollment . Without knowledge of primary treatment assignment in ADAPT , participants were grouped by their self-reported use of lipid-lowering agents ( LLA ) . In the current ancillary ADAPT study we found that elective statin use was associated with significantly reduced risk of incident AD after adjustment for age , gender , education and Apolipoprotein E ( ApoE ) genotype . The findings were similar when comparing all LLA use ( statin and non-statin LLA ) to non-LLA use . Cholesterol levels were lower among statin users compared with non-LLA users , but the MMSE scores were equivalent . The data suggest that statin therapy may be of benefit in reducing the risk of AD BACKGROUND Throughout the usual LDL cholesterol range in Western population s , lower blood concentrations are associated with lower cardiovascular disease risk . In such population s , therefore , reducing LDL cholesterol may reduce the development of vascular disease , largely irrespective of initial cholesterol concentrations . METHODS 20,536 UK adults ( aged 40 - 80 years ) with coronary disease , other occlusive arterial disease , or diabetes were r and omly allocated to receive 40 mg simvastatin daily ( average compliance : 85 % ) or matching placebo ( average non- study statin use : 17 % ) . Analyses are of the first occurrence of particular events , and compare all simvastatin-allocated versus all placebo-allocated participants . These " intention-to-treat " comparisons assess the effects of about two-thirds ( 85 % minus 17 % ) taking a statin during the scheduled 5-year treatment period , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( about two-thirds of the effect of actual use of 40 mg simvastatin daily ) . Primary outcomes were mortality ( for overall analyses ) and fatal or non-fatal vascular events ( for subcategory analyses ) , with subsidiary assessment s of cancer and of other major morbidity . FINDINGS All-cause mortality was significantly reduced ( 1328 [ 12.9 % ] deaths among 10,269 allocated simvastatin versus 1507 [ 14.7 % ] among 10,267 allocated placebo ; p=0.0003 ) , due to a highly significant 18 % ( SE 5 ) proportional reduction in the coronary death rate ( 587 [ 5.7 % ] vs 707 [ 6.9 % ] ; p=0.0005 ) , a marginally significant reduction in other vascular deaths ( 194 [ 1.9 % ] vs 230 [ 2.2 % ] ; p=0.07 ) , and a non-significant reduction in non-vascular deaths ( 547 [ 5.3 % ] vs 570 [ 5.6 % ] ; p=0.4 ) . There were highly significant reductions of about one-quarter in the first event rate for non-fatal myocardial infa rct ion or coronary death ( 898 [ 8.7 % ] vs 1212 [ 11.8 % ] ; p<0.0001 ) , for non-fatal or fatal stroke ( 444 [ 4.3 % ] vs 585 [ 5.7 % ] ; p<0.0001 ) , and for coronary or non-coronary revascularisation ( 939 [ 9.1 % ] vs 1205 [ 11.7 % ] ; p<0.0001 ) . For the first occurrence of any of these major vascular events , there was a definite 24 % ( SE 3 ; 95 % CI 19 - 28 ) reduction in the event rate ( 2033 [ 19.8 % ] vs 2585 [ 25.2 % ] affected individuals ; p<0.0001 ) . During the first year the reduction in major vascular events was not significant , but subsequently it was highly significant during each separate year . The proportional reduction in the event rate was similar ( and significant ) in each subcategory of participant studied , including : those without diagnosed coronary disease who had cerebrovascular disease , or had peripheral artery disease , or had diabetes ; men and , separately , women ; those aged either under or over 70 years at entry ; and --most notably -- even those who presented with LDL cholesterol below 3.0 mmol/L ( 116 mg/dL ) , or total cholesterol below 5.0 mmol/L ( 193 mg/dL ) . The benefits of simvastatin were additional to those of other cardioprotective treatments . The annual excess risk of myopathy with this regimen was about 0.01 % . There were no significant adverse effects on cancer incidence or on hospitalisation for any other non-vascular cause . INTERPRETATION Adding simvastatin to existing treatments safely produces substantial additional benefits for a wide range of high-risk patients , irrespective of their initial cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rates of myocardial infa rct ion , of stroke , and of revascularisation by about one-quarter . After making allowance for non-compliance , actual use of this regimen would probably reduce these rates by about one-third . Hence , among the many types of high-risk individual studied , 5 years of simvastatin would prevent about 70 - 100 people per 1000 from suffering at least one of these major vascular events ( and longer treatment should produce further benefit ) . The size of the 5-year benefit depends chiefly on such individuals ' overall risk of major vascular events , rather than on their blood lipid concentrations alone OBJECTIVE To determine the effect of lovastatin therapy on health-related quality of life in older persons . DESIGN A prospect i ve , r and omized , double blind clinical trial . SETTING Four university medical center research clinics . PARTICIPANTS There were 431 men and women , primarily 65 years of age or older , with low density lipoprotein levels greater than 159 mg/dL and less than 221 mg/dL. Exclusion criteria included a Mini-Mental state score less than 24 or presence of recent cardiovascular events or other serious chronic disease likely to shorten survival . INTERVENTION All participants were administered the National Cholesterol Education Program step one diet and were then r and omized to placebo , 20 mg lovastatin , or 40 mg lovastatin . MEASUREMENTS Areas of health-related quality of life assessed in the Cholesterol Reduction in Seniors Program ( CRISP ) included : ( 1 ) physical functioning , ( 2 ) sleep behavior , ( 3 ) social support , ( 4 ) depression , ( 5 ) cognitive function , and ( 6 ) health perception . Three global change questions asked the patients to judge change in general health since starting the study diet or the study medication and change in ability to function or care for self . Although some patients were followed for a total of 12 months , all participants were followed for 6 months , and 6-month data have been used for the primary analysis in this paper . RESULTS Patients treated with 20 mg of lovastatin had a 17 % and 24 % reduction in total cholesterol and LDL-cholesterol , respectively . Patients treated with the 40-mg lovastatin dose achieved reductions of 20 % for total cholesterol and 28 % for LDL-cholesterol . Complaints of possible adverse events were remarkably similar in the two active treatment groups and the placebo group . At 6 months of follow-up there were no statistically significant differences found in mean change scores from baseline between treatment groups on the health-related quality of life measures ( physical functioning , sleep , social support , depression , cognitive function scales , health perception ) or global questions . CONCLUSIONS This study demonstrates that lovastatin was extremely well tolerated in an older cohort , both with regard to symptoms and to health-related quality of life BACKGROUND The statin treatment of dyslipidemia is associated with a reduced risk of development of Alzheimer disease ( AD ) . The effect may be mediated by a reduction in cholesterol bio synthesis in the brain , by lowering levels of apolipoprotein E ( apo E)-containing lipoproteins , or by pleitropic effects such as reduction in beta-amyloid production . In the brain , cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase ( CYP46 ) . The oxysterol is subsequently transferred across the blood-brain barrier , transported to the liver by low-density lipoproteins ( LDLs ) , and excreted as bile acids . Most of plasma 24S-hydroxycholesterol is derived from brain cholesterol ; consequently , plasma levels of the oxysterol reflect brain cholesterol catabolism . OBJECTIVE To examine the effect of 3 statins and a nonstatin hypolipidemic agent on plasma levels of 24S-hydroxycholesterol and apo E in patients with AD . STUDY DESIGN The study had a sequential parallel design . It was open-labeled and involved lipoprotein and 24S-hydroxycholesterol evaluations at baseline and at 6 weeks of treatment with 40 mg of lovastatin , simvastatin , or pravastatin sodium per day , or 1 g of extended-release niacin per day . Blood sample s were drawn after a 12-hour fast for measurement of plasma sterols , oxysterols , lipoprotein cholesterol , and levels of apo E , plasma transaminases , and glucose . Measurements were made at baseline and during treatment . RESULTS Statin treatment reduced levels of plasma lathosterol by 49.5 % , 24S-hydroxycholesterol by 21.4 % , LDL cholesterol by 34.9 % , and total cholesterol by 25 % . The ratios of lathosterol-campesterol and 24S-hydroxycholesterol-LDL cholesterol were reduced significantly , but the ratio of 24S-hydroxycholesterol-total cholesterol was unchanged . Extended-release niacin also significantly reduced levels of 24S-hydroxycholesterol by 10 % and LDL cholesterol by 18.1 % . None of the agents lowered plasma concentration of apo E. CONCLUSIONS Statins lowered levels of plasma 24S-hydroxycholesterol without affecting levels of apo E. The LDL lowering was more pronounced than 24S-hydroxycholesterol reductions . The effect of statins on LDL partially explains the reduction of plasma oxysterol level Objective : To assess the association between statin therapy and risk of Alzheimer disease ( AD ) in a prospect i ve cohort study with documented statin exposure and incident dementia . Methods : This is a prospect i ve , cohort study of statin use and incident dementia and probable AD . A cohort of 2,356 cognitively intact persons , aged 65 and older , were r and omly selected from a health maintenance organization ( HMO ) , and were assessed biennially for dementia . Statin use was identified using the HMO pharmacy data base . A proportional hazards model with statin use as a time-dependent covariate was used to assess the statin – dementia/AD association . Results : Among 312 participants with incident dementia , 168 had probable AD . The unadjusted hazard ratios ( HRs ) with statin use were 1.33 ( 95 % CI 0.95 to 1.85 ) for all-cause dementia and 0.90 ( CI 0.54 to 1.51 ) for probable AD . Adjusted corresponding HRs were 1.19 ( CI 0.82 to 1.75 ) and 0.82 ( CI 0.46 to 1.46 ) . A subgroup analysis of participants with at least one APOE-ε4 allele who entered the study before age 80 produced an adjusted HR of 0.33 ( CI 0.10 to 1.04 ) . Conclusion : Employing time-dependent proportional hazards modeling , the authors found no significant association between statin use and incident dementia or probable AD . In contrast , when the data were analyzed , inappropriately , as a case-control study , the authors found an OR of 0.55 for probable AD , falsely indicating a protective effect of statins . Study design and analytic methods may explain the discrepancy between the current null findings and earlier findings BACKGROUND / AIMS Hypercholesterolemia in midlife increases risk for Alzheimer 's disease ( AD ) and contributes to cerebrovascular dysregulation - an early finding in pre clinical AD pathology . Statins improve vascular reactivity , but it is unknown if they increase regional cerebral blood flow ( CBF ) in individuals at risk for AD . METHODS In a r and omized , controlled , double-blind pilot study , 16 asymptomatic middle-aged adults with parental history of AD were r and omized to atorvastatin or placebo daily for 4 months . At baseline and month 4 , regional CBF was measured using arterial spin-labeling magnetic resonance imaging and endothelial function was measured using brachial artery ultrasound . RESULTS At baseline , participants with low HDL-cholesterol , higher global vascular risk , and greater endothelial dysfunction had reduced regional CBF in areas of the brain related to memory and learning ( all p < 0.03 ) . Using voxel-based analysis , 4 months of atorvastatin increased CBF in bilateral hippocampi , fusiform gyrus , putamen and insular cortices compared to placebo . CONCLUSION In this pilot study , atorvastatin increased regional CBF in persons at risk for AD . Further research is warranted to confirm whether statins increase CBF in areas of the brain related to memory and learning and whether such perfusion changes are associated with a delay in the onset of AD . CLINICAL TRIAL REGISTRATION http:// clinical trials.gov Identifier : NCT00751907 |
2,156 | 25,408,915 | Intervention and participant characteristics did not predict success in decreasing depressive symptoms .
Conclusions Indicated prevention and early intervention programs targeting eating disorder symptoms are limited in their success in decreasing concurrent depressive symptoms . | Background Depressive and eating disorder symptoms are highly comorbid .
To date , however , little is known regarding the efficacy of existing programs in decreasing concurrent eating disorder and depressive symptoms . | Abstract The goal of this study was to develop a cognitive – behavioral self-help manual for anorexia nervosa . Patients diagnosed with anorexia nervosa ( N=102 ) , binge eating/purging type ( AN-B/P ) , were consecutively assigned to one of two conditions : 6-week manualized guided self-help or a wait-list control . All patients thereafter received inpatient treatment in a hospital for behavioral medicine . The primary outcome variable was the number of days in inpatient treatment . Secondary outcome variables were measures of psychopathology . Results showed that duration of inpatient treatment was significantly shorter ( by 5.2 days ) among participants receiving guided self-help . Body image , slimness ideal , general psychopathology , and some bulimic symptoms improved significantly during self-help . The authors conclude that , to increase effects of therapist-guided self-help in AN-B/P , additional variants of a self-help manual should be tried in different therapeutic setting The present study investigated the efficacy of self-help based on cognitive behaviour therapy in combination with Internet support in the treatment of bulimia nervosa and binge eating disorder . After confirming the diagnosis with an in-person interview , 73 patients were r and omly allocated to treatment or a waiting list control group . Treated individuals showed marked improvement after 12 weeks of self-help compared to the control group on both primary and secondary outcome measures . Intent-to-treat analyses revealed that 37 % ( 46 % among completers ) had no binge eating or purging at the end of the treatment and a considerable number of patients achieved clinical ly significant improvement on most of the other measures as well . The results were maintained at the 6-month follow-up , and provide evidence to support the continued use and development of self-help programmes OBJECTIVE The objective was to examine the effectiveness of a self-help treatment as a first line primary care intervention for binge eating disorder ( BED ) in obese patients . This study compared the effectiveness of a usual care plus self-help version of cognitive behavioral therapy ( shCBT ) to usual care ( UC ) only in ethnically/racially diverse obese patients with BED in primary care setting s in an urban center . METHOD 48 obese patients with BED were r and omly assigned to either shCBT ( N = 24 ) or UC ( N = 24 ) for four months . Independent assessment s were performed monthly throughout treatment and at post-treatment . RESULTS Binge-eating remission rates did not differ significantly between shCBT ( 25 % ) and UC ( 8.3 % ) at post-treatment . Mixed models of binge eating frequency determined using the Eating Disorder Examination ( EDE ) revealed significant decreases for both conditions but that shCBT and UC did not differ . Mixed models of binge eating frequency from repeated monthly EDE- question naire assessment s revealed a significant treatment-by-time interaction indicating that shCBT had significant reductions whereas UC did not during the four-month treatments . Mixed models revealed no differences between groups on associated eating disorder psychopathology or depression . No weight loss was observed in either condition . CONCLUSIONS Our findings suggest that pure self-help CBT did not show effectiveness relative to usual care for treating BED in obese patients in primary care . Thus , self-help CBT may not have utility as a front-line intervention for BED for obese patients in primary care and future studies should test guided-self-help methods for delivering CBT in primary care generalist setting OBJECTIVE A group dissonance-based eating disorder prevention program , in which young women critique the thin ideal , reduces eating disorder risk factors and symptoms , but it can be difficult to identify school clinicians with the time and expertise to deliver the intervention . Thus , we developed a prototype Internet version of this program and evaluated it in a preliminary trial . METHOD Female college students with body dissatisfaction ( N = 107 ; M age = 21.6 years , SD = 6.6 ) were r and omized to the Internet intervention , group intervention , educational video condition , or educational brochure condition . RESULTS Internet and group participants showed greater pre-post reductions in eating disorder risk factors and symptoms than video controls ( M ds = 0.47 and 0.54 , respectively ) and brochure controls ( M ds = 0.75 and 0.72 , respectively ) , with many effects reaching significance . Effects did not differ significantly for Internet versus group participants ( M ds = -0.13 ) or for video versus brochure controls ( M d = 0.25 ) . Effect sizes for the Internet intervention were similar to those previously observed for group versions of this intervention . CONCLUSIONS Results suggest that this prototype Internet intervention is as efficacious as the group intervention , implying that there would be merit in completing this intervention and evaluating it in a fully powered trial This study evaluated a targeted intervention design ed to alleviate body image and eating problems in adolescent girls that was delivered over the internet so as to increase access to the program . The program consisted of six , 90-minute weekly small group , synchronous on-line sessions and was facilitated by a therapist and manual . Participants were 73 girls ( mean age=14.4 years , SD=1.48 ) who self-identified as having body image or eating problems and were r and omly assigned to an intervention group ( n=36 ) ( assessed at baseline , post-intervention and at 2- and 6-months follow-up ) or a delayed treatment control group ( n=37 ) ( assessed at baseline and 6–7 weeks later ) . Clinical ly significant improvements in body dissatisfaction , disordered eating , and depression were observed at post-intervention and maintained at follow-up . Internet delivery was enthusiastically endorsed . The program offers a promising approach to improve body image and eating problems that also addresses geographic access problems The purpose of this study was to conduct an assessment of binge eating severity among obese persons . Two question naires were developed . A 16-item Binge Eating Scale was constructed describing both behavioral manifestations ( e.g. , eating large amounts of food ) and feeling/cognitions surrounding a binge episode ( e.g. , guilt , fear of being unable to stop eating ) . An 11-item Cognitive Factors Scale was developed measure two cognitive phenomena thought to be related to binge eating : the tendency to set unrealistic st and ards for a diet ( e.g. , eliminating " favorite foods " ) and low efficacy expectations for sustaining a diet . The results showed that the Binge Eating Scale successfully discriminated among persons judged by trained interviewers to have either no , moderate or severe binge eating problems . Significant correlation between the scales were obtained such that severe bingers tended to set up diets which were unrealistically strict while reporting low efficacy expectations to sustain a diet . The discussion highlighted the differences among obese persons on binge eating severity and emphasized the role of cognitions in the relapse of self control of eating OBJECTIVE This study examined the outcome of a body image and disordered eating intervention for midlife women . The intervention was specifically design ed to address risk factors that are pertinent in midlife . METHOD Participants were 61 women aged 30 to 60 years ( M = 43.92 , SD = 8.22 ) r and omly assigned to intervention ( n = 32 ) or ( delayed treatment ) control ( n = 29 ) groups . Following an 8-session facilitated group cognitive behavioral therapy-based intervention , outcomes from the Body Shape Question naire ; Eating Disorder Examination Question naire ; Body Image Avoidance Question naire ; Physical Appearance Comparison Scale ; Sociocultural Attitudes Towards Appearance Scale , Internalization subscale ; measures of appearance importance , cognitive re appraisal , and self-care ; Dutch Eating Behavior Question naire ; and Kessler Psychological Distress Scale were compared for statistical and clinical significance from baseline to posttest and 6-month follow-up . RESULTS Following the intent-to-treat principle , mixed-model analyses with a mixed within-between design demonstrated that the intervention group had large improvements that were statistically significantly different from the control group in body image , disordered eating , and risk factor variables and that were maintained at 6-month follow-up . Furthermore , the improvements were also of clinical importance . CONCLUSIONS This study provides support for the efficacy of an intervention to reduce body image and eating concerns in midlife women . Further research into interventions tailored for this population is warranted We performed a r and omized controlled study to test the relative efficacy of guided self-help ( gsh ) cognitive-behavioral therapy ( CBTgsh ) and behavioral weight loss treatment ( BWLgsh ) treatments for binge eating disorder ( BED ) . To provide an additional partial control for non-specific influences of attention , a third control ( CON ) treatment condition was included . We tested the treatments using a guided self-help approach given the promising results from initial studies using minimal therapist guidance . Ninety consecutive overweight patients ( 19 males , 71 females ) with BED were r and omly assigned ( 5:5:2 ratio ) to one of three treatments : CBTgsh ( N=37 ) , BWLgsh ( N=38 ) , or CON ( N=15 ) . The three 12-week treatment conditions were administered individually following guided self-help protocol s. Overall , 70 ( 78 % ) completed treatments ; CBTgsh ( 87 % ) and CON ( 87 % ) had significantly higher completion rates than BWLgsh ( 67 % ) . Intent-to-treat analyses revealed that CBTgsh had significantly higher remission rates ( 46 % ) than either BWLgsh ( 18 % ) or CON ( 13 % ) . Weight loss was minimal and differed little across treatments . The findings suggest that CBT , administered via guided self-help , demonstrates efficacy for BED , but not for obesity . The findings support CBT administered via guided self-help as a first step in the treatment of BED and provide evidence for its specific effects CONTEXT Eating disorders , an important health problem among college-age women , may be preventable , given that modifiable risk factors for eating disorders have been identified and interventions have been evaluated to reduce these risk factors . OBJECTIVE To determine if an Internet-based psychosocial intervention can prevent the onset of eating disorders ( EDs ) in young women at risk for developing EDs . SETTING San Diego and the San Francisco Bay Area in California . PARTICIPANTS College-age women with high weight and shape concerns were recruited via campus e-mails , posters , and mass media . Six hundred thirty-seven eligible participants were identified , of whom 157 were excluded , for a total sample of 480 . Recruitment occurred between November 13 , 2000 , and October 10 , 2003 . Intervention A r and omized controlled trial of an 8-week , Internet-based cognitive-behavioral intervention ( Student Bodies ) that included a moderated online discussion group . Participants were studied for up to 3 years . MAIN OUTCOME MEASURES The main outcome measure was time to onset of a sub clinical or clinical ED . Secondary measures included change in scores on the Weight Concerns Scale , Global Eating Disorder Examination Question naire , and Eating Disorder Inventory drive for thinness and bulimia subscales and depressed mood . Moderators of outcome were examined . RESULTS There was a significant reduction in Weight Concerns Scale scores in the Student Bodies intervention group compared with the control group at postintervention ( P < .001 ) , 1 year ( P < .001 ) , and 2 years ( P < .001 ) . The slope for reducing Weight Concerns Scale score was significantly greater in the treatment compared with the control group ( P = .02 ) . Over the course of follow-up , 43 participants developed sub clinical or clinical EDs . While there was no overall significant difference in onset of EDs between the intervention and control groups , the intervention significantly reduced the onset of EDs in 2 subgroups identified through moderator analyses : ( 1 ) participants with an elevated body mass index ( BMI ) ( > or = 25 , calculated as weight in kilograms divided by height in meters squared ) at baseline and ( 2 ) at 1 site , participants with baseline compensatory behaviors ( eg , self-induced vomiting , laxative use , diuretic use , diet pill use , driven exercise ) . No intervention participant with an elevated baseline BMI developed an ED , while the rates of onset of ED in the comparable BMI control group ( based on survival analysis ) were 4.7 % at 1 year and 11.9 % at 2 years . In the subgroup with a BMI of 25 or higher , the cumulative survival incidence was significantly lower at 2 years for the intervention compared with the control group ( 95 % confidence interval , 0 % for intervention group ; 2.7 % to 21.1 % for control group ) . For the San Francisco Bay Area site sample with baseline compensatory behaviors , 4 % of participants in the intervention group developed EDs at 1 year and 14.4 % , by 2 years . Rates for the comparable control group were 16 % and 30.4 % , respectively . CONCLUSIONS Among college-age women with high weight and shape concerns , an 8-week , Internet-based cognitive-behavioral intervention can significantly reduce weight and shape concerns for up to 2 years and decrease risk for the onset of EDs , at least in some high-risk groups . To our knowledge , this is the first study to show that EDs can be prevented in high-risk groups Previous research has addressed the issues of behavior change and eating disorder prevention among adolescents and young women . The current study was design ed to evaluate : ( a ) whether an 8-week psychoeducational intervention can reduce maladaptive weight-management practice s in women ( University females , N=24 ) with sub- clinical levels of eating pathology ; and ( b ) whether its implementation reduces the risk of developing more severe eating pathology across time . Participants were r and omly assigned to an experimental ( EX ) group or a self-monitoring control ( SMC ) group . Statistically significant changes on measures of eating pathology , including the Eating Attitudes Test-26 [ Garner , D. M. , Olmsted , M. P. , Bohr , Y. , & Garfinkel , P. ( 1982 ) . The Eating Attitudes Test : psychometric features and clinical correlates . Psychological Medicine , 12 , 871 - 878 ] ; Forbidden Food Survey [ Ruggerio , L. , Williamson , D. A. , Davis , C. J. , Schlundt , D. G. , & Carey , M. P. ( 1988 ) . Forbidden Food Survey : Measure of bulimic 's anticipated emotional reactions to specific foods . Addictive Behaviors , 13 , 267 - 274 ] ; and Bulimia Test-Revised [ Thelen , M. H. , Farmer , J. , Wonderlich , S. , & Smith , M. ( 1991 ) . A revision of the bulimia test : The BULIT-R. Journal of Consulting and Clinical Psychology , 3(1 ) , 119 - 124 ] were observed , as were changes in body image , as measured by the Body Shape Question naire [ Cooper , P. J. , Taylor , M. J. , Cooper , Z. , & Fairburn , C. G. ( 1987 ) . The development and validation of the body shape question naire . International Journal of Eating Disorders , 6(4 ) , 485 - 494 ] . Additional significant between-group differences in eating behavior , as measured by daily meal records , were also seen . Participants in the EX group evidence d improvements in scores which were significantly different from those observed in the SMC group . Unfortunately , attrition limited the utility of follow up data Binge eating disorder ( BED ) is a common and under-treated condition with major health implication s. Cognitive behavioural therapy ( CBT ) self-help manuals have proved to be efficient in BED treatment . Increasing evidence also support the use of new technology to improve treatment access and dissemination . This is the first r and omised controlled study to evaluate the efficacy of an Internet guided self-help treatment programme , based on CBT , for adults with threshold and subthreshold BED . Seventy-four women were r and omised into two groups . The first group received the six-month online programme with a six-month follow-up . The second group was placed in a six-month waiting list before participating in the six-month intervention . Guidance consisted of a regular e-mail contact with a coach during the whole intervention . Binge eating behaviour , drive for thinness , body dissatisfaction and interoceptive awareness significantly improved after the Internet self-help treatment intervention . The number of objective binge episodes , overall eating disorder symptoms score and perceived hunger also decreased . Improvements were maintained at six-month follow-up . Dropouts exhibited more shape concern and a higher drive for thinness . Overall , a transfer of CBT-based self-help techniques to the Internet was well accepted by patients , and showed positive results for eating disorders psychopathology BACKGROUND Women reporting initial eating disorder ( ED ) symptoms are at highest risk for the development of an eating disorder . Preventive interventions should , therefore , be specifically tailored for this subgroup . AIMS To adapt and evaluate the effects of the Internet-based prevention program " Student Bodies ™ " for women with symptoms of disordered eating and /or subthreshold eating disorder ( ED ) syndromes . METHOD 126 women , reporting subthreshold ED symptoms ( high weight and shape concerns and below threshold bingeing , purging , chronic dieting or several of these symptoms ) were r and omly assigned to a Student Bodies ™ + ( SB+ ) intervention or a wait-list control group and assessed at pre-intervention , post-intervention , and 6-month follow-up . " Student Bodies ™ " was adapted to be suitable for subthreshold EDs . Main outcome measures were attitudes and symptoms of disordered eating . Pre-follow-up data were analyzed by ANCOVAS with mixed effects . RESULTS At 6-month follow-up , compared to participants in the control group , participants in the intervention group showed significantly greater improvements on ED-related attitudes . Intervention participants also showed 67 % ( 95 % CI = 20 - 87 % ) greater reductions in combined rates of subjective and objective binges , and 86 % ( 95 % CI = 63 - 95 % ) greater reduction in purging episodes . Also , the rates of participants abstinent from all symptoms of disordered eating ( restrictive eating , binge eating and any compensatory behavior ) were significantly higher in the intervention group ( 45.1 % vs. 26.9 % ) . Post-hoc subgroup analyses revealed that for participants with binge eating the effect on EDE-Q scores was larger than in the pure restricting subgroup . CONCLUSION The adapted " SB+ " program represents an effective intervention for women with subthreshold EDs of the binge eating subtype OBJECTIVE Efficacy trials found that a dissonance-based eating disorder prevention program in which female high school and college students with body image concerns critique the thin ideal reduced eating disorder risk factors , eating disorder symptoms , and future eating disorder onset . The present effectiveness trial tested whether this program produces effects through long-term follow-up when high school clinicians recruit students and deliver the intervention under real-world conditions . METHOD Female high school students with body image concerns ( N = 306 ; M age = 15.7 years , SD = 1.1 ) were r and omized to the dissonance intervention or an educational brochure control condition and completed assessment s through 3-year follow-up . RESULTS Dissonance participants showed significantly greater decreases in body dissatisfaction at 2-year follow-up and eating disorder symptoms at 3-year follow-up than controls ; effects on other risk factors , risk for eating disorder onset , and other outcomes ( e.g. , body mass ) were marginal or nonsignificant . CONCLUSIONS Although it was encouraging that some key effects persisted over long-term follow-up , effects were on average smaller in this effectiveness trial than previous efficacy trials , which could be due to ( a ) facilitator selection , training , and supervision ; ( b ) the lower risk status of participants ; or ( c ) the use of a control condition that produces some effects OBJECTIVE The present preliminary trials tested whether undergraduate peer leaders can effectively deliver a dissonance-based eating disorder prevention program , which could facilitate broad dissemination of this efficacious intervention . METHOD In Study 1 , female undergraduates ( N=171 ) were r and omized to peer-led groups , clinician-led groups , or an educational brochure control condition . In Study 2 , which improved a design limitation of Study 1 by using completely parallel outcome measures across conditions , female undergraduates ( N=148 ) were r and omized to either immediate peer-led groups or a waitlist control condition . RESULTS In Study 1 , participants in peer- and clinician-led groups showed significantly greater pre-post reductions in risk factors and eating disorder symptoms than controls ( M d=.64 and .98 respectively ) , though clinician- versus peer-led groups had higher attendance and competence ratings , and produced stronger effects at posttest ( M d=.32 ) and at 1-year follow-up ( M d=.26 ) . In Study 2 , participants in peer-led groups showed greater pre-post reductions in all outcomes than waitlist controls ( M d=.75 ) . CONCLUSIONS Results provide novel evidence that dissonance-based eating disorder prevention groups led by undergraduate peers are feasible and produce greater reductions in eating disorder risk factors and symptoms than minimal-intervention control conditions , but indicate that effects are smaller for peer- versus clinician-led groups BACKGROUND To increase access to cognitive behavioural therapy for bulimia nervosa new delivery modes are being examined . Guided Self-Help ( GSH ) in primary care is potentially valuable in this respect . This research aim ed to compare outcomes following GSH delivered by general practitioners ( GPs ) in the normal course of their practice to a delayed treatment control ( DTC ) condition , and to examine the maintenance of treatment gains at 3 and 6 months following completion of GSH . METHOD Participants were 109 women with full syndrome or sub-threshold bulimia nervosa , r and omly allocated to GSH ( n = 54 ) and DTC ( n = 55 ) . The GSH group received direction and support from a GP over a 17-week period while working through the manual in Bulimia Nervosa and Binge-Eating : A Guide to Recovery by P. J. Cooper ( 1995 ) . GSH and DTC groups were assessed pre-treatment and 1 week following the 17-week intervention or waiting interval . The GSH group was reassessed at 3- and 6-month follow-up . RESULTS Intention-to-treat analyses at end of treatment revealed significant improvements in bulimic and psychological symptoms in GSH compared with DTC , reduction in mean frequency of binge-eating episodes by 60 % in GSH and 6 % in DTC , and remission from all binge-eating and compensatory behaviours in 28 % of the GSH and 11 % of the DTC sample . Treatment gains were maintained at 3- and 6-month follow-up . CONCLUSION Outcomes in GSH compare favourably with those of specialist-delivered psychological treatments . These findings are considered in light of the nature of the therapy offered and the primary care context OBJECTIVE Evaluate a selective prevention program targeting both eating disorder symptoms and unhealthy weight gain in young women . METHOD Female college students at high-risk for these outcomes by virtue of body image concerns ( N = 398 ; M age = 18.4 years , SD = 0.6 ) were r and omized to the Healthy Weight group-based 4-hr prevention program , which promotes gradual lasting healthy improvements to dietary intake and physical activity , or an educational brochure control condition . RESULTS Compared to controls , intervention participants showed significantly greater reductions in body dissatisfaction and eating disorder symptoms , and greater increases in physical activity , at posttest and significantly greater reductions in body mass index ( BMI ) and self-reported dieting at 6-month follow-up . Moderator analyses revealed significantly greater reductions in eating disorder symptoms for those with initially elevated symptoms and pressure to be thin and significantly greater reductions in BMI for those with initially elevated eating disorder symptoms . CONCLUSIONS Results indicate that this intervention reduced both eating disorder symptoms and unhealthy weight gain , but suggest it should be improved to produce stronger and more persistent effects , and that it may be useful to target young women with both body image and eating disturbances OBJECTIVE Efficacy trials indicate that a dissonance-based prevention program in which female high school and college students with body image concerns critique the thin-ideal reduced risk factors , eating disorder symptoms , and future eating disorder onset , but weaker effects emerged from an effectiveness trial wherein high school clinicians recruited students and delivered the program under real-world conditions . The present effectiveness trial tested whether a new enhanced dissonance version of this program produced larger effects when college clinicians recruited students and delivered the intervention using improved procedures to select , train , and supervise clinicians . METHOD Young women recruited from seven universities across the US ( N = 408 , M age = 21.6 , SD = 5.64 ) were r and omized to the dissonance intervention or an educational brochure control condition . RESULTS Dissonance participants showed significantly greater decreases in risk factors ( thin-ideal internalization , body dissatisfaction , dieting , negative affect ) and eating disorder symptoms versus controls at posttest and 1-year follow-up , result ing in medium average effect size ( d = .60 ) . Dissonance participants also reported significant improvements in psychosocial functioning , but not reduced health care utilization or unhealthy weight gain . CONCLUSIONS This novel multisite effectiveness trial with college clinicians found that the enhanced dissonance version of this program and the improved facilitator selection /training procedures produced average effects that were 83 % larger than effects observed in the high school effectiveness trial OBJECTIVE Because conventional preventive interventions have had little success in reducing eating pathology , we developed and evaluated a more intensive psychoeducational intervention . METHOD Female college students who underwent this intervention and a matched control sample of students ( N = 66 ) completed pretest and posttest surveys . RESULTS Intervention participants showed significant decreases in thin-ideal internalization , body dissatisfaction , dieting , eating disorder symptoms , and weight over the 4-month study period , whereas matched control participants did not show changes in these outcomes with the exception that they gained weight . DISCUSSION These preliminary findings suggest that this intervention may prove useful in reducing eating disturbances and overweight among college students , as well as the risk factors for this serious mental and physical health problem One hundred and ten people in an university population responded to emailed eating disorder question naires . Ninty-seven fulfilling criteria for eating disorders ( bulimia nervosa ( BN ) , binge eating disorder ( BED ) , EDNOS ) were r and omised to therapist administered email bulimia therapy ( eBT ) , unsupported Self directed writing ( SDW ) or Waiting list control ( WLC ) . Measures were repeated at 3 months . Diagnosis , Beck depression inventory ( BDI ) and Bulimia investigatory test ( BITE ) scores were recorded . Follow-up rate was 63 % and results must be interpreted cautiously . However significantly fewer participants who had received eBT or SDW fulfilled criteria for eating disorders at follow up compared to WLC . There was no significant difference between eBT and SDW in the analysis of variance ( ANOVA ) , although in separate analyses , eBT was significantly superior to WLC ( p < 0.02 ) and the difference for SDW approached significance ( p = 0.06 ) . BDI and BITE scores showed no significant change . For eBT participants there was a significant positive correlation between words written and improvement in BITE severity score . BN , BED and EDNOS can be treated via email OBJECTIVE Despite proven efficacy of cognitive behavioral therapy ( CBT ) for treating eating disorders with binge eating as the core symptom , few patients receive CBT in clinical practice . Our blended efficacy-effectiveness study sought to evaluate whether a manual-based guided self-help form of CBT ( CBT-GSH ) , delivered in 8 sessions in a health maintenance organization setting over a 12-week period by master's-level interventionists , is more effective than treatment as usual ( TAU ) . METHOD In all , 123 individuals ( mean age = 37.2 ; 91.9 % female , 96.7 % non-Hispanic White ) were r and omized , including 10.6 % with bulimia nervosa ( BN ) , 48 % with binge eating disorder ( BED ) , and 41.4 % with recurrent binge eating in the absence of BN or BED . Baseline , posttreatment , and 6- and 12-month follow-up data were used in intent-to-treat analyses . RESULTS At 12-month follow-up , CBT-GSH result ed in greater abstinence from binge eating ( 64.2 % ) than TAU ( 44.6 % ; number needed to treat = 5 ) , as measured by the Eating Disorder Examination ( EDE ) . Secondary outcomes reflected greater improvements in the CBT-GSH group in dietary restraint ( d = 0.30 ) ; eating , shape , and weight concern ( ds = 0.54 , 1.01 , 0.49 , respectively ; measured by the EDE Question naire ) ; depression ( d = 0.56 ; Beck Depression Inventory ) ; and social adjustment ( d = 0.58 ; Work and Social Adjustment Scale ) , but not weight change . CONCLUSIONS CBT-GSH is a viable first-line treatment option for the majority of patients with recurrent binge eating who do not meet diagnostic criteria for BN or anorexia nervosa Predictors and moderators of outcomes were examined in 75 overweight patients with binge-eating disorder ( BED ) who participated in a r and omized clinical trial of guided self-help treatments . Age variables , psychiatric and personality disorder comorbidity , and clinical characteristics were tested as predictors and moderators of treatment outcomes . Current age and age of BED onset did not predict outcomes . Key dimensional outcomes ( binge frequency , eating psychopathology , and negative affect ) were predominately predicted , but not moderated , by their respective pretreatment levels . Presence of personality disorders , particularly Cluster C , predicted both posttreatment negative affect and eating disorder psychopathology . Negative affect , but not major depressive disorder , predicted attrition , posttreatment negative affect , and eating disorder psychopathology . Despite the prognostic significance of these findings for dimensional outcomes , none of the variables tested were predictive of binge remission ( i.e. , a categorical outcome ) . No moderator effects were found . The present study found poorer prognosis for patients with negative affect and personality disorders , suggesting that treatment outcomes may be enhanced by attending to the cognitive and personality styles of these patients BACKGROUND Bulimic eating disorders are common among female students , yet the majority do not access effective treatment . Internet-based cognitive-behavioural therapy ( iCBT ) may be able to bridge this gap . METHOD Seventy-six students with bulimia nervosa ( BN ) or eating disorder not otherwise specified ( EDNOS ) were r and omly assigned to immediate iCBT with e-mail support over 3 months or to a 3-month waiting list followed by iCBT [ waiting list/delayed treatment control ( WL/DTC ) ] . ED outcomes were assessed with the Eating Disorder Examination ( EDE ) at baseline , 3 months and 6 months . Other outcomes included depression , anxiety and quality of life . RESULTS Students who had immediate iCBT showed significantly greater improvements at 3 and 6 months than those receiving WL/DTC in ED and other symptoms . CONCLUSIONS iCBT with e-mail support is efficacious in students with bulimic disorders and has lasting effects OBJECTIVE Eating-disordered behavior is prevalent among college women . Few interventions have successfully reduced risk factors for these behaviors , however . The most promising interventions are both selective and interactive . This study compared two newer types of interventions that meet these criteria : cognitive dissonance and yoga programs . METHOD This study advertised programs for women who were dissatisfied with their bodies . Participants ( N = 93 ) were r and omly assigned to dissonance , yoga , or control groups . RESULTS Hierarchical regression analyses revealed that there were no significant post-intervention differences between the yoga and control groups . Dissonance group participants had significantly lower scores than the scores of both other groups on measures of disordered eating , drive for thinness , body dissatisfaction , alexithymia , and anxiety . CONCLUSION These findings have important implication s for interventions on college campuses . In particular , dissonance interventions appear to be an efficient and inexpensive approach to reducing eating disorder risk factors . Additional research regarding the value of yoga interventions is needed OBJECTIVE The authors examined the effectiveness of unguided self-help as a first step in the treatment of bulimia nervosa . METHOD A total of 85 women with bulimia nervosa who were on a waiting list for treatment at a hospital-based clinic participated . The patients were r and omly assigned to receive one of two self-help manuals or to a waiting list control condition for 8 weeks . One of the self-help manuals addressed the specific symptoms of bulimia nervosa ( cognitive behavior self-help ) , while the other focused on self-assertion skills ( nonspecific self-help ) . RESULTS Twenty patients ( 23.5 % ) dropped out of the study . The data were analyzed with intention-to-treat analysis . Although the group-by-time interaction for binge eating and purging was not statistically significant , simple effects showed that there was a significant reduction in symptom frequency in both self-help conditions at posttreatment but not in the waiting list condition . There were no statistically significant changes in levels of dietary restraint , eating concerns , concerns about shape and weight , or general psychopathology . A greater proportion of patients in the cognitive behavior self-help ( 53.6 % ) and nonspecific self-help ( 50.0 % ) conditions reported at least a 50 % reduction in binge eating or purging at posttreatment , compared with the waiting list condition ( 31.0 % ) . A lower baseline knowledge about eating disorders , more problems with intimacy , and higher compulsivity scores predicted a better response . CONCLUSIONS The findings suggest that a subgroup of patients with bulimia nervosa may benefit from unguided self-help as a first step in their treatment . Cognitive behavior self-help and nonspecific self-help had equivalent effects Because depressive and bulimic pathologies often co-occur among adolescent girls , a preventive program focusing on both disturbances would have clinical utility . Thus , we developed a cognitive-behavioral intervention targeting body dissatisfaction , an established risk factor for both conditions . A r and omized prevention trial with late adolescent girls suggested that the intervention reduced body dissatisfaction , negative affect , depressive symptoms , and bulimic symptoms , but not dieting . Effects persisted through 3-month follow-up , but most faded by 6-month follow-up . Intervention effects on negative affect , depressive symptoms , and bulimic symptoms appeared to be mediated by change in body dissatisfaction . Participant age , ethnicity , and body mass did not moderate intervention effects . Results suggest that an intervention that improves body satisfaction might reduce depressive and bulimic symptoms but imply that greater emphasis on preventing future symptoms might be necessary for persistent effects OBJECTIVE The aim of this study was to compare the outcomes following an eight-session , small group , therapist-led , intervention for body dissatisfaction , and disordered eating in adult women , delivered either in face-to-face or synchronous , internet mode . METHOD Community women with high body dissatisfaction and internet access were r and omly assigned to either face-to-face delivery ( N = 42 ) , internet delivery ( N = 37 ) , or delayed treatment control ( N = 37 ) . All groups were assessed at baseline and 8 - 9 weeks later . The intervention groups were reassessed at 6-months follow-up . RESULTS Both intervention groups showed large improvements in body dissatisfaction compared with the delayed treatment control and these improvements were maintained at follow-up . However , posttreatment improvements were greater in the face-to-face than internet intervention . CONCLUSION In adult women , it is desirable to deliver the body image intervention in a face-to-face mode , but the internet mode is effective and has the potential to increase access to therapy |
2,157 | 26,891,915 | Comparison of the available studies showed lower maximum concentrations ( Cmax ) and exposure ( AUC ) of dihydroartemisinin , the active metabolite of all artemisinin derivatives , after oral administration of artemether , artesunate and dihydroartemisinin in pregnant women .
Low day 7 concentrations were commonly seen in lumefantrine studies , indicating a low exposure and possibly reduced efficacy .
The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinical ly relevant .
Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy , while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence .
For atovaquone , the available data showed a lower maximum concentration and exposure .
Finally , the maximum concentration of cycloguanil , the active metabolite of proguanil , was significantly lower , possibly compromising the efficacy .
Conclusion These findings suggest that re assessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women . | Abstract Background Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs , including the different components of artemisinin-based combination therapy ( ACT ) .
However , small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies .
The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations . | Abstract Objective : Atovaquone plus proguanil is a new , well-tolerated and highly effective antimalarial drug . In order to protect it from the development of resistance , it may be deployed in combination with an artemisinin derivative . To investigate whether artesunate affects the pharmacokinetics of atovaquone plus proguanil , and to provide preliminary information regarding the tolerability of the triple drug combination ( artesunate plus atovaquone plus proguanil ) , a cross over study was conducted in adult volunteers . Methods : Twelve healthy Karen adults were r and omised to receive atovaquone-proguanil ( 1000/400 mg ) with or without artesunate ( 250 mg ) and , at least 90 days later , the study was repeated . Blood was sample d over a 10-day period . Results : The three-drug combination was well tolerated . Artesunate did not alter the pharmacokinetic properties of atovaquone and proguanil ( maximum plasma concentrations : 13.02 μg/ml and 742 ng/ml ; elimination half-lives : 42.2 h and 14.4 h ; oral plasma clearance estimates : 90 ml/h/kg and 710 ml/h/kg ; and apparent volumes of distribution : 4.9 l/kg and 14.5 l/kg , respectively ) . There was also no effect of artesunate on the biotransformation of proguanil to cycloguanil . The pharmacokinetic variables were similar to those reported previously for the individual drugs . Conclusion : Artesunate does not influence atovaquone or proguanil pharmacokinetics . The triple-drug combination of atovaquone and proguanil and artesunate was well tolerated The efficacy of artemether and artemether followed by mefloquine was evaluated in 45 pregnant women with drug resistant Plasmodium falciparum malaria during the second and third trimesters . There was prompt clinical response to both treatment regimens . The parasite and fever clearance times and the cure rate were similar in both groups . Except for the correlation between initial parasite density and fever clearance time in the artemether-mefloquine group , there was no correlation between initial parasite density and parasite or fever clearance times in the two groups . Similarly , there was no correlation between parasite and fever clearance . Both treatment regimens were well tolerated . All newborn babies of the participating women were normal at birth . Physical and neurodevelopmental assessment of the newborn babies followed up for a period varying between 6 and 36 months were within normal limits . Artemether alone or with mefloquine are effective and do not produce undue deleterious effects in pregnant patients with drug-resistant falciparum malaria during the second and third trimesters To compare the effectiveness and safety of quinine sulfate and artesunate with mefloquine for treating second trimester pregnancy in women who suffered from Plasmodium falciparum malaria . The prospect i ve study was done in Srisangwal Hospital , Mae Hong Son , Thail and . Sixty , second to third trimester pregnant patients with P. falciparum infection , were recruited at r and om . They received either quinine sulfate 10 mg/kg/day for at least 7 days , 29 women ( group I ) , or oral artesunate 2 mg/kg as the first dose , 1 mg/kg every 12 hours orally for at least 5 days together with split doses of mefloquine , 15 mg/kg and 6 hours later 10 mg/kg orally 1 day after artesunate was stopped , 28 women ( group II ) . Three cases ( 5 % ) were lost to follow-up before delivery , one case in group I and two cases in group II . After treatment , the mean hematocrit of group I was significantly less than group II ( p = 0.000 ) . The PCT ( parasite clearance time ) and FCT ( fever clearance time ) of group II were significantly shorter than group I ( p = 0.000 ) . None of the patients in both groups had recrudescences within 28 days . Group I had more adverse effects than group II . No adverse neurological effects in pregnancy were found in both groups . The calcification of placenta and IUGR ( Intrauterine growth retard ) were not different between the two groups ( p = 0.964 , 0.363 respectively ) . The PCT was not different between the calcified placenta group and normal placenta group ( p = 0.058 ) , but the TTPP ( Total time of parasite presentation ) was ( p = 0.000 ) . TTPP related to low birth weight and low apgar score at 1 minute might be the cause ( p = 0.000 , 0.000 F = 5.261 , 21.627 respectively ) . TTPP and PCT related to neonatal blood pH and caused low neonatal blood pH ( p = 0.000 , 0.001 F = 24.351 , 11.162 respectively ) . The physical and neurological development of the babies at 2 , 4 , 6 and 12 months follow-up , were normal and there were no congenital abnormalities in either group . TTPP relating to fetal outcome , the longer the TTPP , the worse the fetal outcome , so we should diagnose early and treat P. falciparum malaria in pregnancy to prevent fetal jeopardy . Artesunate with mefloquine could shorten the PCT more than quinine sulfate in pregnancy , so the fetal outcome was better than that of quinine sulfate . In cases of prolonged infection before treatment , artesunate might be the alternative treatment of P. falciparum malaria in pregnancy . However , its safety should be carefully studied further with a larger sample size Objective New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance . We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre , Malawi . Methods / Findings This was a r and omized open-label clinical trial , conducted at two rural health centers in Blantyre district , Malawi . A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and r and omly allocated to 3 treatment groups : sulfadoxine-pyrimethamine ( SP ; 3 tablets , 500 mg sulfadoxine and 25 mg pyrimethamine per tablet ) ; SP plus azithromycin ( 1 g/day × 2 days ) ; or SP plus artesunate ( 200 mg/day × 3 days ) . Women received two doses administered at least 4 weeks apart . Heteroduplex tracking assays were performed to distinguish recrudescence from new infections . Main outcome measures were incidence of adverse outcomes , parasite and fever clearance times and recrudescence rates . All treatment regimens were well tolerated . Two women vomited soon after ingesting azithromycin . The parasite clearance time was significantly faster in the SP-artesunate group . Recrudescent episodes of malaria were less frequent with SP-azithromycin [ Hazard Ratio 0.19 ( 95 % confidence interval 0.06 to 0.63 ) ] and SP-artesunate [ Hazard Ratio 0.25 ( 95 % confidence interval 0.10 to 0.65 ) ] compared with SP monotherapy . With one exception ( an abortion in the SP-azithromycin group ) , all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes . Because of the small sample size , the effect on birth outcomes , maternal malaria or maternal anemia could not be evaluated . Conclusions Both SP-artesunate and SP-azithromycin appeared to be safe , well tolerated and efficacious for the treatment of malaria during pregnancy . A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes . Trial Registration ClinialTrials.gov OBJECTIVE : To investigate the pharmacokinetics , safety and efficacy of the recommended 3-day treatment regimen of Malarone in third-trimester pregnant women with acute uncomplicated falciparum malaria . METHODS : Twenty-six pregnant women in their third trimester ( gestational age : 24–34 weeks ) with acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrollment criteria were recruited from the antenatal clinics of Mae Sot Hospital , Tak Province , Thail and , ( n=8 ) and the Tropical Diseases Research Centre , Ndola , Zambia ( n=18 ) . Patients were treated with four Malarone tablets ( GlaxoSmithKline : each tablet contains 250 mg atovaquone and 100 mg proguanil ) once daily for 3 consecutive days . Blood sample s were taken for pharmacokinetic investigations of atovaquone , proguanil , and cycloguanil up to 288 h ( day 14 ) after the last dose . Urine sample s were collected for the evaluation of proguanil and cycloguanil 0–8 , 8–16 , 16–24 and 24–48 h after the last dose . Efficacy assessment s included the clinical and parasitological evaluation of mothers and newborns . Adverse events were evaluated at each visit to the antenatal clinics . RESULTS : Malarone appeared to be effective and well tolerated when used for the treatment of falciparum malaria in pregnant women . All patients showed prompt clinical improvement and the disappearance of parasitaemia after treatment . There were no serious adverse effects or unexpected adverse effects and no stillbirths or spontaneous abortions . The plasma concentration-time profiles of atovaquone and proguanil in most cases were best characterised by the two-compartment open model with zero-order input with/without absorption lag time and first-order elimination . There were no significant differences in any of the pharmacokinetic parameters of atovaquone , proguanil or cycloguanil between patients from Thail and and Zambia . For atovaquone , a Cmax of 1.33–8.33 μg/ml was reached at 2.0–9.3 h after the last dose on day 2 . V/F , CL/F and t1/2β were 6.9–39.5 l/kg , 83–384 ml/h/kg , and 57.8–130.8 h , respectively . The Cmax and tmax values for proguanil versus cycloguanil were 383–918 versus 0–129 ng/ml and 3.3–8.6 versus 3–12 h , respectively . V/F , CL/F , and t1/2β values for proguanil were 10.7–34.0 l/kg , 431–1,662 ml/h/kg and 11.2–30.3 h. The CLR-CG , t1/2z , CG , proguanil/cycloguanil metabolic ratios , AUC ratios for proguanil to cycloguanil ( AUCPG/CG ) were 107.2–1,001 ml/h/kg , 5–95 ml/h/kg , 7.8–20.7 h , 5–57 , and 4.7–20.2 , respectively . CONCLUSION : The pharmacokinetics of atovaquone and cycloguanil appeared to be influenced by the pregnancy status , result ing in an decrease in the Cmax and AUC of approximately twofold Malaria during pregnancy is associated with maternal and fetal morbidity and mortality . In order to minimize the burden , sulfadoxine – pyrimethamine ( SP ) is widely used in Africa as an intermittent preventive treatment of malaria in pregnancy ( IPTp ) . However , only limited data are available on the pharmacokinetics of sulfadoxine and pyrimethamine during pregnancy . We conducted a prospect i ve , self‐matched , multicenter study of 98 pregnant women in four African countries in order to determine the effects of pregnancy on SP pharmacokinetics . After adjusting for the effects of potential confounders , blood concentrations ( associated with therapeutic efficacy ) of pyrimethamine were higher ( geometric mean ratio ( GMR ) 1.33 ; 95 % confidence interval ( CI ) 1.18–1.51 ; P < 0.001 ) and those of sulfadoxine were lower ( GMR 0.91 ; 95 % CI 0.84–0.98 ; P = 0.013 ) on day 7 after SP administration during pregnancy than after the postpartum period . SP pharmacokinetic parameters differed significantly among the study sites . Given the inconsistency of changes in pharmacokinetic parameters between sulfadoxine and pyrimethamine as well as among the study sites , it is not possible to recommend any dose adjustment to prolong the therapeutic life span of the fixed dose combination of SP for IPTp on the basis of our study findings BACKGROUND There is no safe , practical , and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum . METHODS We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a r and omized , open-label trial with a restricted sequential trial design of 7 days of supervised quinine ( SQ7 ) versus 3 days of artesunate-atovaquone-proguanil ( AAP ) . RESULTS Eight-one pregnant women entered the study between December 2001 and July 2003 ; 42 were treated with SQ7 and 39 were treated with AAP . Fever , parasite clearance , and duration of anemia were significantly better with AAP ; the treatment failure rate was 7 times lower ( 5 % [ 2/39 ] vs. 37 % [ 15/41 ] ; relative risk , 7.1 [ 95 % confidence interval , 1.7 - 29.2 ] ; P = .001 ) . There were no significant differences in birth weight , duration of gestation , or congenital abnormality rates in newborns or in growth and developmental parameters of infants monitored for 1 year . CONCLUSION AAP is a well-tolerated , effective , practical , but expensive treatment for multidrug-resistant falciparum malaria during the second or third trimesters of pregnancy . Despite the small number of subjects , our results add to the growing body of evidence that AAP is safe for the mother and the fetus Background To date no comparative trials have been done , to our knowledge , of fixed-dose artemisinin combination therapies ( ACTs ) for the treatment of Plasmodium falciparum malaria in pregnancy . Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world . The objective of this study was to compare the efficacy , tolerability , and safety of artemether-lumefantrine , the most widely used fixed ACT , with 7 d artesunate monotherapy in the second and third trimesters of pregnancy . Methods and Findings An open-label r and omised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d ( AL ) or artesunate monotherapy 7 d ( AS7 ) was conducted in Karen women in the border area of northwestern Thail and who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy . The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery , as estimated by Kaplan-Meier survival analysis . Infants were assessed at birth and followed until 1 y of life . Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy . Both regimens were very well tolerated . The cure rates ( 95 % confidence interval ) for the intention to treat ( ITT ) population were : AS7 89.2 % ( 82.3%–96.1 % ) and AL 82.0 % ( 74.8%–89.3 % ) , p = 0.054 ( ITT ) ; and AS7 89.7 % ( 82.6%–96.8 % ) and AL 81.2 % ( 73.6%–88.8 % ) , p = 0.031 ( per- protocol population ) . One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up . Birth outcomes and infant ( up to age 1 y ) outcomes did not differ significantly between the two groups . The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL . Conclusion The current st and ard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with uncomplicated falciparum malaria , but efficacy was inferior to 7 d artesunate monotherapy and was unsatisfactory for general deployment in this geographic area . Reduced efficacy probably results from low drug concentrations in later pregnancy . A longer or more frequent AL dose regimen may be needed to treat pregnant women effectively and should now be evaluated . Parasitological endpoints in clinical trials of any antimalarial drug treatment in pregnancy should be extended to delivery or day 42 if it comes later . Trial Registration : Current Controlled Trials IS RCT Background The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy . However , the effects of pregnancy on the pharmacokinetics of artemisinin derivatives , such as artesunate ( AS ) , are poorly understood . In this analysis , the population pharmacokinetics of oral AS , and its active metabolite dihydroartemisinin ( DHA ) , were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC . Methods Data were obtained from 26 pregnant women in the second ( 22 - 26 weeks ) or the third ( 32 - 36 weeks ) trimester of pregnancy and from 25 non-pregnant female controls . All subjects received 200 mg AS . Plasma AS and DHA were measured using a vali date d LC-MS method . Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling . Results A simultaneous parent-metabolite model was developed consisting of mixed zero-order , lagged first-order absorption of AS , a one-compartment model for AS , and a one-compartment model for DHA . Complete conversion of AS to DHA was assumed . The model displayed satisfactory goodness-of-fit , stability , and predictive ability . Apparent clearance ( CL/F ) and volume of distribution ( V/F ) estimates , with 95 % bootstrap confidence intervals , were as follows : 195 L ( 139 - 285 L ) for AS V/F , 895 L/h ( 788 - 1045 L/h ) for AS CL/F , 91.4 L ( 78.5 - 109 L ) for DHA V/F , and 64.0 L/h ( 55.1 - 75.2 L/h ) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant , with a pregnancy-associated increase in DHA CL/F of 42.3 % ( 19.7 - 72.3 % ) . Conclusions In this analysis , pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS . These findings , in conjunction with a previous non-compartmental analysis of the modelled data , provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls BACKGROUND Malaria infection during pregnancy is a major public health problem . Due to increasing resistance to Chloroquine and Sulphadoxine/Pyrimethamine , the Ug and an national policy on malaria treatment was changed in 2005 to Artemisinin-based combination therapy ( ACT ) as the first-line treatment for uncomplicated malaria . The policy recommends assessment of safety and efficacy of alternative drugs for treatment of uncomplicated malaria . We compared the efficacy and safety of Artemether-Lumefantrine ( Coartem ) and Chlorproguanil-Dapsone ( Lapdap ) in the management of uncomplicated malaria in pregnancy . METHODOLOGY We enrolled 110 pregnant women in the second and third trimester of pregnancy who presented to Mulago hospital , Ug and a , with uncomplicated malaria . The study design was an open-label r and omized clinical trial . Participants were r and omized to receive either Artemether-Lumefantrine ( Coartem 20 mg/120 mg ) orally or Chlorproguanil-Dapsone ( Lapdap ) orally for 3 consecutive days . Primary endpoints were clinical and parasitological response assessed on days 0 , 1 , 2 , 4 , 7 , 14 and 28 . Adverse effects , clinical response ( treatment failure ) and parasitological response were compared . Analysis was by intention to treat . RESULTS Of the 100 women who completed the study , there was no statistically significant difference in clinical and parasitological response by Day 4 . The mean fever clearance time 3.0 days with Lapdap versus 2.5 days with Coartem was comparable . Likewise , mean parasite clearance time of 2.4 and 2.2 days for Lapdap and Coartem respectively was comparable . The adverse effects were comparable between the two groups . CONCLUSION Artemether-Lumefantrine and Chlorproguanil-Dapsone have high and comparable cure rates and similar safety profiles when used for treatment of uncomplicated malaria in pregnancy BACKGROUND Malaria in pregnancy is associated with maternal and fetal morbidity and mortality . In 2006 , WHO recommended use of artemisinin-based combination treatments during the second or third trimesters , but data on efficacy and safety in Africa were scarce . We aim ed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara , Ug and a. METHODS We did an open-label , r and omised , non-inferiority trial between October , 2006 , and May , 2009 , at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Ug and a. Pregnant women were r and omly assigned ( 1:1 ) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine , and were followed up weekly until delivery . Our primary endpoint was cure rate at day 42 , confirmed by PCR . The non-inferiority margin was a difference in cure rate of 5 % . Analysis of efficacy was for all r and omised patients without study deviations that could have affected the efficacy outcome . This study was registered with Clinical Trials.gov , number NCT00495508 . FINDINGS 304 women were r and omly assigned , 152 to each treatment group . By day 42 , 16 patients were lost to follow-up and 25 were excluded from the analysis . At day 42 , 137 ( 99.3 % ) of 138 patients taking artemether-lumefantrine and 122 ( 97.6 % ) of 125 taking quinine were cured-difference 1.7 % ( lower limit of 95 % CI -0.9 ) . There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group . INTERPRETATION Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy . FUNDING Médecins Sans Frontières and the European Commission Background Intermittent preventive treatment in pregnancy ( IPTp ) with sulfadoxine-pyrimethamine ( SP ) is recommended in HIV-negative women to avert malaria , while this relies on cotrimoxazole prophylaxis ( CTXp ) in HIV-positive women . Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high . The cost-effectiveness of IPTp with alternative drugs is needed to inform policy . Methods The cost-effectiveness of 2-dose IPTp-mefloquine ( MQ ) was compared with IPTp-SP in HIV-negative women ( Benin , Gabon , Mozambique and Tanzania ) . In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone ( Kenya , Mozambique and Tanzania ) . The outcomes used were maternal clinical malaria , anaemia at delivery and non-obstetric hospital admissions . The poor tolerability to MQ was included as the value of women ’s loss of working days . Incremental cost-effectiveness ratios ( ICERs ) were calculated and threshold analysis undertaken . Results For HIV-negative women , the ICER for IPTp-MQ versus IPTp-SP was 136.30 US$ ( 2012 US$ ) ( 95%CI 131.41 ; 141.18 ) per disability-adjusted life-year ( DALY ) averted , or 237.78 US$ ( 95%CI 230.99 ; 244.57 ) , depending on whether estimates from Gabon were included or not . For HIV-positive women , the ICER per DALY averted for IPTp-MQ added to CTXp , versus CTXp alone was 6.96 US$ ( 95%CI 4.22 ; 9.70 ) . In HIV-negative women , moderate shifts of variables such as malaria incidence , drug cost , and IPTp efficacy increased the ICERs above the cost-effectiveness threshold . In HIV-positive women the intervention remained cost-effective for a substantial ( up to 21 times ) increase in cost per tablet . Conclusions Addition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women . IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women . However , the poor tolerability of MQ does not favour its use as IPTp . Regardless of HIV status , prevention of malaria in pregnancy with a highly efficacious , well tolerated antimalarial would be cost-effective despite its high price . Trials Registration Clinical Trials.gov NCT 00811421 ; Pan African Trials Registry PACTR2010020001429343 and A trial was conducted in 32 Thai children with uncomplicated multidrug-resistant falciparum malaria to assess the efficacy , safety and pharmacokinetics of atovaquone and proguanil ; plasma concentrations of atovaquone , proguanil and its metabolite , cycloguanil , were measured in a subset of 9 children . The children received atovaquone ( 17 mg/kg/d for 3 d ) plus proguanil ( 7 mg/kg/d for 3 d ) . Twenty-six children who had only Plasmodium falciparum infection and remained in hospital for 28 d were assessed for drug efficacy . The combination regimen produced a cure rate of 100 % . Parasite and fever clearance times were 47 h ( range 8 - 75 ) and 50 h ( range 7 - 111 ) , respectively . Atovaquone and proguanil were rapidly absorbed , with median time to peak concentrations of 6 h ( range 6 - 24 ) and 6 h ( range 6 - 12 ) , respectively . Peak concentrations of cycloguanil were achieved between 6 and 12 h ( median 6 ) after administration of proguanil . Mean peak plasma concentration of atovaquone on day 3 was 5.1 micrograms/mL ( SD = 2.1 ) . The day 3 mean peak plasma concentration of proguanil was 306 ng/mL ( SD = 108 ) compared with 44.3 ng/mL ( SD = 27.3 ) for cycloguanil . Mean values for the AUC ( area under plasma concentration-time curve ) were 161.8 micrograms/mL.h ( SD = 126.9 ) for atovaquone , 4646 ng/mL.h ( SD = 1226 ) for proguanil , and 787 ng/mL.h ( SD = 397 ) for cycloguanil . Terminal elimination half-lives of atovaquone , proguanil and cycloguanil were estimated as 31.8 h ( SD = 8.9 ) , 14.9 h ( SD = 3.3 ) and 14.6 h ( SD = 2.6 ) , respectively . No major adverse effect was attributable to the study drugs . Atovaquone/proguanil combination is safe and highly effective , and should be especially valuable for treatment of multidrug-resistant falciparum malaria Objective To determine the effects of late pregnancy and also oestrogen supplementation on the CYP2C19-mediated biotransformation of proguanil ( PG ) to its active antifol triazine metabolite cycloguanil ( CG ) . Methods Case control study conducted on the NW border of Thail and ; a single dose of PG ( 4 mg/kg ) was administered to Karen women in late pregnancy and a single blood and urine sample taken 6 h later . Women were studied in late pregnancy ( > 36 weeks ) and restudied 2 months after delivery . A separate cohort of Karen women newly attending a birth-control clinic were studied before and 3 weeks into their first course of oral contraceptives ( OCP : levonorgestrel 0.15 mg and ethinyloestradiol 0.03 mg ) . Forty-five pregnant women and forty-two healthy OCP users were studied . Results The results were similar in both groups ; pregnancy and OCP use were both associated with reduced formation of cycloguanil ( CG ) . Impaired PG biotransformation was seen in women with the " extensive metaboliser " phenotype ( urine PG/CG ratio < 10 ) . CG levels , adjusted for dose , were a median ( range ) 73 % ( −59 to 420 % ) higher following the pregnancy than during the pregnancy in women characterised as extensive metabolisers ( P<0.001 ) . CG levels in women characterised as extensive metabolisers were 34 % ( −54 to 323 % ) higher before than while taking the OCP ( P<0.01 ) . Conclusion Late pregnancy and OCP use impair biotransformation of the active antimalarial metabolite CG from the parent PG . This may be mediated by oestrogen inhibition of CYP2C19 activity . The dose of PG should be increased by 50 % in these groups ABSTRACT In order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy , 24 pregnant women in the second and third trimesters of pregnancy and with Plasmodium vivax malaria were treated with amodiaquine ( 10 mg/kg of body weight/day ) for 3 days . The same women were studied again at 3 months postpartum . Plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-t and em mass spectrometry method . Individual concentration-time data were evaluated using noncompartmental analysis . There were no clinical ly relevant differences in the pharmacokinetics of amodiaquine and desethylamodiaquine between pregnant ( n = 24 ) and postpartum ( n = 18 ) women . The results suggest that the current amodiaquine dosing regimen is adequate for the treatment of P. vivax infections during pregnancy OBJECTIVES Mefloquine/artesunate has recently been developed as a fixed-dose combination , providing a promising rescue/alternative treatment for malaria during pregnancy . However , limited data are available on the effect of pregnancy on its pharmacokinetic properties . This study was conducted to assess the pharmacokinetic properties of mefloquine/carboxymefloquine and artesunate/dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria . METHODS Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled . All patients were treated for uncomplicated Plasmodium falciparum malaria with a st and ard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days . Frequent blood sample s were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses . The study was registered at www . clinical trials.gov ( identifier : NCT00701961 ) . RESULTS The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women ( P>0.05 ) . There was a trend of higher exposure to mefloquine in the pregnant women , but this difference did not reach statistical significance ( 656700 versus 542400 h × ng/mL ; P=0.059 ) . However , the total exposure to carboxymefloquine was 49 % lower during pregnancy ( 735600 versus 1499000 h × ng/mL ; P<0.001 ) and the total drug exposure to artesunate was 42 % higher during pregnancy ( 89.0 versus 62.9 h × ng/mL ; P=0.039 ) compared with non-pregnant controls . CONCLUSIONS The plasma levels of mefloquine and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant women , but there were significant differences in carboxymefloquine and artesunate exposure . The data presented here do not warrant a dose adjustment in pregnant patients , but an extensive analysis of the data could provide a better underst and ing of these findings Background Malaria in pregnancy is serious , and drug resistance in Africa is spreading . Drugs have greater risks in pregnancy and determining the safety and efficacy of drugs in pregnancy is therefore a priority . This study set out to determine the efficacy and safety of several antimalarial drugs and combinations in pregnant women with uncomplicated malaria . Methods Pregnant women with non-severe , slide proven , falciparum malaria were r and omised to one of 4 regimes : sulfadoxine-pyrimethamine [ SP ] ; chlorproguanil-dapsone [ CD ] ; SP+amodiaquine [ SP+AQ ] or amodiaquine+artesunate [ AQ+AS ] . R and omisation was on a 1∶2∶2∶2 ratio . Women were admitted for treatment , and followed at days 7 , 14 , 21 , 28 after the start of treatment , at delivery and 6 weeks after delivery to determine adverse events , clinical and parasitological outcomes . Primary outcome was parasitological failure by day 28 . Results 1433 pregnant women were screened , of whom 272 met entry criteria and were r and omised ; 28 to SP , 81 to CD , 80 to SP+AQ and 83 to AQ+AS . Follow-up to day 28 post treatment was 251/272 ( 92 % ) , and to 6 weeks following delivery 91 % . By day 28 parasitological failure rates were 4/26 ( 15 % , 95%CI 4–35 ) in the SP , 18/77 ( 23 % , 95%CI 14–34 ) in the CD , 1/73 ( 1 % 95%CI 7–0.001 ) in the SP+AQ and 7/75 ( 9 % 95%CI 4–18 ) in the AQ+AS arms respectively . After correction by molecular markers for reinfection the parasitological failure rates at day 28 were 18 % for CD , 1 % for SP+AQ and 4.5 % for AQ+AS . There were two maternal deaths during the trial . There was no apparent excess of stillbirths or adverse birth outcomes in any arm . Parasitological responses were strikingly better in pregnant women than in children treated with the same drugs at this site . Conclusions Failure rates with monotherapy were unacceptably high . The two combinations tested were efficacious and appeared safe . It should not be assumed that efficacy in pregnancy is the same as in children . Trial Registration Clinical Trials.gov Aim The aim was to compare the pharmacokinetic properties of artesunate and dihydroartemisinin in the same women : i ) pregnant with acute uncomplicated malaria on day 1 and 2 , ii ) pregnant with convalescent malaria on day 7 and iii ) in a healthy state 3 months post-partum on day 1 , 2 and 7 . Methods Non-linear mixed-effects modelling was used to compare plasma concentration – time profiles of artesunate and dihydroartemisinin over 7 days of treatment following oral and intravenous artesunate administration to pregnant women with uncomplicated Plasmodium falciparum malaria during their second or third trimesters of pregnancy . The same women were restudied 3 months after delivery when fully recovered . Non-compartmental results of the same study have been published previously . Results Twenty pregnant patients on the Thail and -Myanmar border were studied and 15 volunteered to be restudied 3 months post-partum . Malaria and pregnancy had no effect on the pharmacokinetic properties of artesunate or dihydroartemisinin after intravenous artesunate administration . However , malaria and pregnancy had opposite effects on the absorption of orally administered artesunate . Malaria increased the absolute oral bioavailability of artesunate by 87 % , presumably by inhibiting first pass effect , whereas pregnancy decreased oral bioavailability by 23 % . Conclusions The population pharmacokinetic analysis demonstrated opposite effects of malaria and pregnancy on the bioavailability of orally administered artesunate . Lower drug exposures during the second and third trimesters of pregnancy may contribute to lower cure rates and thus the development of drug resistance . Dose optimization studies are required for artesunate containing artemisinin-based combination therapies ( ACTs ) in later pregnancy Objective To determine the pharmacokinetic properties of atovaquone , proguanil , and the triazine metabolite cycloguanil in women with recrudescent multi-drug resistant falciparum malaria during the second and third trimesters of pregnancy treated by artesunate-atovaquone-proguanil . Methods Serial plasma concentrations of atovaquone , proguanil and cycloguanil were measured in 24 women at baseline and after the final dose of the 3-day treatment with atovaquone ( 20 mg/kg/day ) plus proguanil ( 8 mg/kg/day ) plus artesunate ( 4 mg/kg/day ) daily . Results The triple combination was well tolerated and highly effective . The outcomes of pregnancy were all normal . Population mean ( ± SEM ) oral clearance ( Cl/F ) estimates were 313±33 ml/h/kg and 1109±43 ml/h/kg , total apparent volume of distribution ( Vd/F ) 13.0±1.3 l/kg and 22.9±1.4 l/kg , and terminal elimination half-life ; 29.1 h and 14.3 h , for atovaquone and proguanil , respectively . Using conventional and population pharmacokinetic analyses , Cl/F and Vd/F estimates for both drugs were approximately twice , and plasma concentrations less than half those reported previously in healthy subjects and patients with acute malaria . Conclusion Artesunate-atovaquone-proguanil is a promising treatment for multi-drug resistant falciparum malaria during pregnancy , but the dose of atovaquone-proguanil may need to be increased ABSTRACT The tolerability , safety , and disposition of dihydroartemisinin ( DHA ) and piperaquine ( PQ ) were assessed in 32 pregnant ( second/third trimester ) and 33 nonpregnant Papua New Guinean women r and omized to adult treatment courses of DHA-PQ ( three daily doses ) or sulfadoxine-pyrimethamine (SP)-PQ ( three daily PQ doses , single dose of SP ) . All dose adminstrations were observed , and subjects fasted for 2 h postdose . Plasma PQ was assayed by using high-performance liquid chromatography , and DHA was assessed by using liquid chromatography-mass spectrometry . Compartmental pharmacokinetic models were developed using a population -based approach . Both regimens were well tolerated . There was an expected increase in the rate-corrected electrocardiographic QT interval which was independent of pregnancy and treatment . Two pregnant and two nonpregnant women had Plasmodium falciparum parasitemia which cleared within 48 h , and no other subject became slide positive for malaria during 42 days of follow-up . Of 30 pregnant women followed to delivery , 27 ( 90 % ) delivered healthy babies and 3 ( 10 % ) had stillbirths ; these obstetric outcomes are consistent with those in the general population . The area under the plasma PQ concentration-time curve ( AUC0–∞ ) was lower in the pregnant patients ( median [ interquartile range ] , 23,721 μg · h/liter [ 21,481 to 27,951 μg · h/liter ] versus 35,644 μg · h/liter [ 29,546 to 39,541 μg · h/liter ] ; P < 0.001 ) in association with a greater clearance relative to bioavailability ( 73.5 liters/h [ 69.4 to 78.4 ] versus 53.8 liters/h [ 49.7 to 58.2 ] ; P < 0.001 ) , but pregnancy did not influence the pharmacokinetics of DHA . The apparent pharmacokinetic differences between the present study and results from other studies of women with uncomplicated malaria that showed no effect of pregnancy on the AUC0–∞ of PQ and greater bioavailability may reflect differences in postdose fat intake , proportions of women with malaria , and /or racial differences in drug disposition 1 . A dose finding pharmacokinetic study was performed in 20 Karen women in the third trimester of pregnancy receiving antimalarial prophylaxis with mefloquine . Ten received 250 mg mefloquine base weekly and ten received identical tablets of 125 mg base/week . 2 . Both dose regimens were well tolerated . Malaria was prevented effectively , there were no serious adverse effects , all pregnancies proceeded normally , and there were no abnormalities in the babies followed up to 2 years . 3 . The median time from dose administration to peak whole blood mefloquine concentration was 6 ( range 3 - 24 ) h. Mean ( + /- s.d . ) peak and trough concentrations in the seventh week were 722 + /- 279 and 488 + /- 155 ng ml-1 with the 250 mg/week dose , and 390 + /- 81 and 185 + /- 53 ng ml-1 with the 125 mg/week dose regimens respectively . These blood concentration values are lower than those reported previously in non-pregnant adults . 4 . One and two compartmental models were fitted to the whole blood concentration-time data . Mean ( + /- s.d . ) clearance ( CL/F ) was 0.78 + /- 0.27 ml min-1 kg-1 , and the apparent terminal elimination half-life ( t1/2 ) was 11.6 + /- 7.9 days . 5 . Further studies to determine the oral bioavailability of mefloquine are needed , but these results suggest that clearance may be increased in late pregnancy . These preliminary results of good efficacy without significant toxicity are encouraging , and a more extensive evaluation of mefloquine antimalarial prophylaxis in pregnancy is now warranted ABSTRACT To determine the pharmacokinetic disposition of sulfadoxine ( SDOX ) and pyrimethamine ( PYR ) when administered as intermittent presumptive treatment during pregnancy ( IPTp ) for malaria , 30 Papua New Guinean women in the second or third trimester of pregnancy and 30 age-matched nonpregnant women were given a single dose of 1,500 mg of SDOX plus 75 mg of pyrimethamine PYR . Blood was taken at baseline and 1 , 2 , 4 , 6 , 12 , 18 , 24 , 30 , 48 , and 72 h and at 7 , 10 , 14 , 28 , and 42 days posttreatment in all women . Plasma sample s were assayed for SDOX , N-acetylsulfadoxine ( NASDOX ) , and PYR by high-performance liquid chromatography . Population pharmacokinetic modeling was performed using NONMEM v6.2.0 . Separate user-defined mamillary models were fitted to SDOX/NASDOX and PYR . When the covariate pregnancy was applied to clearance , there was a significant improvement in the base model for both treatments . Pregnancy was associated with a significantly lower area under the concentration-time curve from 0 to ∞ for SDOX ( 22,315 versus 33,284 mg·h/liter ) , NASDOX ( 801 versus 1,590 mg·h/liter ) , and PYR ( 72,115 versus 106,065 μg·h/liter ; P < 0.001 in each case ) . Because lower plasma concentrations of SDOX and PYR could compromise both curative efficacy and posttreatment prophylaxis in pregnant patients , IPTp regimens incorporating higher mg/kg doses than those recommended for nonpregnant patients should be considered ABSTRACT Artemether-lumefantrine has become one of the most widely used antimalarial drugs in the world . The objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multidrug-resistant Plasmodium falciparum malaria on the northwestern border of Thail and . Burmese and Karen women ( n = 103 ) with P. falciparum malaria and in the second and third trimesters of pregnancy were treated with artemether-lumefantrine ( 80/480 mg ) twice daily for 3 days . All patients provided five capillary plasma sample s for drug quantification , and the collection times were r and omly distributed over 14 days . The concentration-time profiles of lumefantrine were assessed by nonlinear mixed-effects modeling . The treatment failure rate ( PCR-confirmed recrudescent infections at delivery ) was high ; 16.5 % ( 95 % confidence interval , 9.9 to 25.1 ) . The population pharmacokinetics of lumefantrine were described well by a two-compartment open model with first-order absorption and elimination . The final model included interindividual variability in all pharmacokinetic parameters and a linear covariate relationship between the estimated gestational age and the central volume of distribution . A high proportion of all women ( 40 % , 41/103 ) had day 7 capillary plasma concentrations of < 355 ng/ml ( which corresponds to approximately < 280 ng/ml in venous plasma ) , a threshold previously associated with an increased risk of therapeutic failure in nonpregnant patients in this area . Predictive modeling suggests that a twice-daily regimen given for 5 days would be preferable in later pregnancy . In conclusion , altered pharmacokinetic properties of lumefantrine contribute to the high rates of failure of artemether-lumefantrine treatment in later pregnancy . Dose optimization is urgently needed The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine ( Coartem/Riamet ; Novartis Pharma AG , Basel , Switzerl and ) were assessed in a r and omized trial in 219 patients ( > or = 12 years old ) with acute , uncomplicated Plasmodium falciparum malaria in Thail and . One hundred and sixty-four patients received artemether-lumefantrine and 55 received the st and ard treatment combination of mefloquine-artesunate . Both drugs induced rapid clearance of parasites and malaria symptoms . The 28-day cure rates were 95.5 % ( 90 % confidence interval [ CI ] = 91.7 , 97.9 % ) for artemether-lumefantrine and 100 % ( 90 % CI = 94.5 , 100 % ) for mefloquine-artesunate . This high-dose regimen of artemether-lumefantrine was very well tolerated , with very good compliance . The most frequent adverse events were headache , dizziness , nausea , abdominal pain , dyspepsia , vomiting , and skin rash . Overall , only 2 % of patients in both groups showed QTc prolongations but without any cardiac complication , and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine . Plasma levels of artemether , dihydroartemisinin , and lumefantrine were consistent with historical data for the same dose regimen , and were higher , particularly for lumefantrine , than those previously observed with the four-dose regimen , explaining the greater efficacy of the six-dose regimen in a drug-resistant setting . These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria BACKGROUND Sulfadoxine-pyrimethamine ( SP ) is among the most commonly used antimalarial drugs during pregnancy , yet the pharmacokinetics of SP are unknown in pregnant women . HIV-infected ( HIV(+ ) ) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected ( HIV(- ) ) women . We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP . METHODS Seventeen pregnant HIV(- ) women and 16 pregnant HIV(+ ) women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine . Five HIV(- ) and 6 HIV(+ ) postpartum women returned 2 - 3 months after delivery for another dose . The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups . RESULTS HIV status did not affect the area under the curve ( AUC(0 - ->infinity ) ) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women , although partum status did have a significant affect on sulfadoxine pharmacokinetics . Among prepartum women , the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women ( 148 vs 256 h ; P<.001 ) , and the median AUC(0 - ->infinity ) was ~40 % lower ( 22,816 vs 40,106 microg/mL/h , P<.001 ) . HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics . CONCLUSION Pregnancy significantly modifies the disposition of SP , whereas HIV status has little influence on pharmacokinetic parameters in pregnant women ABSTRACT The pharmacokinetic properties of oral and intravenous artesunate ( 2 mg/kg of body weight ) were studied in 19 adult patients with acute uncomplicated Plasmodium falciparum malaria by using a r and omized crossover design . A sensitive bioassay was used to measure the antimalarial activity in plasma which results from artesunate and its principal metabolite , dihydroartemisinin . The oral study was repeated with 15 patients during convalescence . The mean absolute oral bioavailability of the antimalarial agent in patients with acute malaria was 61 % ( 95 % confidence interval [ CI ] , 52 to 70 % ) . The absorption and elimination of oral artesunate were rapid , with a mean elimination half-life of antimalarial activity of 43 min ( 95 % CI , 33 to 53 min ) . Following oral administration to patients with acute falciparum malaria , peak antimalarial activity in plasma and the area under the plasma concentration-time curve were approximately double those during convalescence and the apparent volume of distribution and clearance were approximately half those during convalescence ( P ≤ 0.005 ) . Acute malaria is associated with a significant reduction in the clearance of artesunate-associated antimalarial activity Since no effective malaria prevention measures have been identified for pregnant women living on the western border of Thail and , prompt diagnosis and efficient treatment are paramount , although drug resistance in Plasmodium falciparum has narrowed the treatment options . An open r and omized comparison of supervised quinine ( 10 mg salt/kg every 8 h ) for 7 days ( Q7 ) versus mefloquine 25 mg base/kg ( total dose ) plus artesunate 4 mg/kg per day for 3 days ( MAS3 ) was conducted in 1995 - 97 in 108 Karen women with acute uncomplicated falciparum malaria in the second or third trimesters of pregnancy . The MAS3 regimen was more effective than the Q7 regimen : day 63 cure rates were 98.2 % ( 95 % CI 94.7 - 100 ) ( n = 65 ) for MAS3 and 67.0 % ( 95 % CI 43x3 - 90x8 ) ( n = 41 ) for Q7 , P = 0x001 . The MAS3 regimen was also associated with less gametocyte carriage ; the average person-gametocyte-weeks for MAS3 was 2.3 ( 95 % CI 0 - 11 ) and for Q7 was 46x9 ( 95 % CI 26 - 78 ) per 1000 person-weeks , respectively ( P < 0.001 ) . MAS3 was significantly better tolerated . These evident advantages must be balanced against a possible increased risk of stillbirth with the use of mefloquine in pregnancy . Further r and omized studies assessing the safety and efficacy of other artemisinin-containing combination regimens in pregnancy are needed urgently |
2,158 | 26,987,641 | Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas .
Research in animals tends to consistently suggest that Δ9-THC depresses glutamate synaptic transmission via CB1 receptor activation , affecting glutamate release , inhibiting receptors and transporters function , reducing enzyme activity , and disrupting glutamate synaptic plasticity after prolonged exposure | Use of cannabis or delta-9-tetrahydrocannabinol ( Δ9-THC ) , its main psychoactive ingredient , is associated with psychotic symptoms or disorder .
However , the neurochemical mechanism that may underlie this psychotomimetic effect is poorly understood .
Although dopaminergic dysfunction is generally recognized as the final common pathway in psychosis , evidence of the effects of Δ9-THC or cannabis use on dopaminergic measures in the brain is equivocal .
In fact , it is thought that cannabis or Δ9-THC may not act on dopamine firing directly but indirectly by altering glutamate neurotransmission . | CONTEXT Cannabis sativa use can impair verbal learning , provoke acute psychosis , and increase the risk of schizophrenia . It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms . OBJECTIVES To investigate the effects of 2 main psychoactive constituents of C. sativa , Delta9-tetrahydrocannabinol ( Delta9-THC ) and cannabidiol , on regional brain function during verbal paired associate learning . DESIGN Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task . Each imaging session was preceded by the ingestion of Delta9-THC ( 10 mg ) , cannabidiol ( 600 mg ) , or placebo in a double-blind , r and omized , placebo-controlled , repeated- measures , within-subject design . SETTING University research center . PARTICIPANTS Fifteen healthy , native English-speaking , right-h and ed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygen level-dependent response ) , performance in a verbal learning task , and objective and subjective ratings of psychotic symptoms , anxiety , intoxication , and sedation . RESULTS Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety , intoxication , and sedation , whereas no significant effect was noted on these parameters following administration of cannabidiol . Performance in the verbal learning task was not significantly modulated by either drug . Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident . Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs , which was directly correlated with concurrently induced psychotic symptoms . In contrast , administration of cannabidiol had no such effect . CONCLUSION The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms , respectively |
2,159 | 26,658,333 | Otherwise , the results revealed no consistent benefits on spasticity in other neurological conditions studied .
There is little evidence that change in spasticity was related to change in functional performance .
There is insufficient evidence to support or refute the notion that whole-body vibration can reduce spasticity in stroke , spinocerebellar ataxia or multiple sclerosis | Objectives : To examine the effects of whole-body vibration on spasticity among people with central nervous system disorders . | Whole‐body vibration ( WBV ) training is commonly practice d and may enhance peripheral blood flow . Here , we investigated muscle morphology and acute microcirculatory responses before and after a 6‐week resistive exercise training intervention without ( RE ) or with ( RVE ) simultaneous whole‐body vibrations ( 20 Hz , 6 mm peak‐to‐peak amplitude ) in 26 healthy men in a r and omized , controlled parallel‐ design study . Total haemoglobin ( tHb ) and tissue oxygenation index ( TOI ) were measured in gastrocnemius muscle ( GM ) with near‐infrared spectroscopy ( NIRS ) . Whole‐body oxygen consumption ( VO2 ) was measured via spirometry , and skeletal muscle morphology was determined in soleus ( SOL ) muscle biopsies . Our data reveal that exercise‐induced muscle deoxygenation both before and after 6 weeks training was similar in RE and RVE ( P = 0·76 ) , although VO2 was 20 % higher in the RVE group ( P<0·001 ) . The RVE group showed a 14%‐point increase in reactive hyperaemia ( P = 0·007 ) and a 27 % increase in blood volume ( P<0·01 ) in GM after 6 weeks of training . The number of capillaries around fibres was increased by 15 % after 6 weeks training in both groups ( P<0·001 ) with no specific effect of superimposed WBV ( P = 0·61 ) . Neither of the training regimens induced fibre hypertrophy in SOL . The present findings suggest an increased blood volume and vasodilator response in GM as an adaptation to long‐term RVE , which was not observed after RE alone . We conclude that RVE training enhances vasodilation of small arterioles and possibly capillaries . This effect might be advantageous for muscle thermoregulation and the delivery of oxygen and nutrients to exercising muscle and removal of carbon dioxide and metabolites Abstract The aim of the study was to compare the effect of an unsupervised whole body vibration ( WBV ) training and two different supervised multi- purpose exercise programmes , with and without WBV , on body composition , functional fitness and self-reported well-being in middle-aged adults . Fifty-four healthy participants ( age 48.6 ± 6.7 years ) were r and omly assigned to a vibration group ( VG ) , a multi- purpose exercise group ( MG ) and a multi- purpose exercise with vibration group ( VMG ) and trained 3 days a week for 4 months . VG performed a st and ardised unsupervised WBV protocol , MG a supervised multi- purpose exercise and VMG a multi- purpose exercise including vibration . After training , drop out was significantly higher in VG group ( P = 0.016 ) when compared to VMG group . In both MG and VMG , body composition , sit-up , push-up , sit and reach , agility test , hopping test and self-reported general health significantly improved ( P < 0.05 ) . No additive effects were generated by the vibration stimulus . Percentage of body fat and agility test in VG had a significant opposite trend compared to VMG group ( P < 0.05 ) . In summary , an unsupervised WBV training should not be chosen for training protocol . However , positive effects on physical fitness and the best results in adherence could be achieved integrating WBV practice into a multi- purpose exercise training This study compared the rate of muscle temperature ( Tm ) increase during acute whole-body vibration ( WBV ) , to that of stationary cycling and passive warm-up . Additionally we wanted to determine if the purported increase in counter-movement jump and peak power cycling from acute WBV could be explained by changes in muscle temperature . Eight active participants volunteered for the study , which involved a rest period of 30 min to collect baseline measures of muscle , core , skin temperature , heart rate ( HR ) , and thermal leg sensation ( TLS ) , which was followed by three vertical jumps and 5 s maximal cycle performance test . A second rest period of 40 min was enforced followed by the intervention and performance tests . The change in Tm elicited during cycling was matched in the hot bath and WBV interventions . Therefore cycling was performed first , proceeded by , in a r and om order of hot bath and acute WBV . The rate of Tm was significantly greater ( P < 0.001 ) during acute WBV ( 0.30 ° C min−1 ) compared to cycle ( 0.15 ° C min−1 ) and hot bath ( 0.09 ° C min−1 ) however there was no difference between the cycle and hot bath , and the metabolic rate was the same in cycling and WBV ( 19 mL kg−1 min−1 ) . All three interventions showed a significant ( P < 0.001 ) increase in countermovement jump peak power and height . For the 5 s maximal cycle test ( MIC ) there were no significant differences in peak power between the three interventions . In conclusion , acute WBV elevates Tm more quickly than traditional forms of cycling and passive warm-up . Given that all three warm-up methods yielded the same increase in peak power output , we propose that the main effect is caused by the increase in Tm OBJECTIVE The aim of this study was to evaluate the effect on spasticity , muscle strength and motor performance after 8 weeks of whole-body vibration training compared with resistance training in adults with cerebral palsy . METHODS Fourteen persons with spastic diplegia ( 21 - 41 years ) were r and omized to intervention with either whole-body vibration training ( n=7 ) or resistance training ( n=7 ) . Pre- and post-training measures of spasticity using the modified Ashworth scale , muscle strength using isokinetic dynamometry , walking ability using Six-Minute Walk Test , balance using Timed Up and Go test and gross motor performance using Gross Motor Function Measure were performed . RESULTS Spasticity decreased in knee extensors in the whole-body vibration group . Muscle strength increased in the resistance training group at the velocity 30 degrees /s and in both groups at 90 degrees /s . Six-Minute Walk Test and Timed Up and Go test did not change significantly . Gross Motor Function Measure increased in the whole-body vibration group . CONCLUSION These data suggest that an 8-week intervention of whole-body vibration training or resistance training can increase muscle strength , without negative effect on spasticity , in adults with cerebral palsy Objective : To examine the effectiveness of whole body vibration ( WBV ) on tone , muscle force , sensation and functional performance in people with multiple sclerosis . Design : A r and omized cross-over pilot study . Setting : Revive MS Support Therapy Centre . Glasgow , UK . Subjects : Sixteen people with multiple sclerosis were r and omly allocated to one of two groups . Intervention : Group 1 received four weeks of whole body vibration plus exercise three times per week , two weeks of no intervention and then four weeks of exercise alone three times per week . Group 2 were given the two treatment interventions in the reverse order to group 1 . Main measures : Ten-metre walk , Timed Up and Go Test , Modified Ashworth Scale , Multiple Sclerosis Spasticity Scale ( MSSS-88 ) , lower limb muscle force , Nottingham Sensory Assessment and Multiple Sclerosis Impact Scale ( MSIS-29 ) were used before and after intervention . Results : The exercise programme had positive effects on muscle force and well-being , but there was insufficient evidence that the addition of whole body vibration provided any further benefit . The Modified Ashworth Scale was generally unaffected by either intervention , although , for each group , results from the MSSS-88 showed whole body vibration and exercises reduced muscle spasms ( P = 0.02 ) . Although results for the 10-m walk and Timed Up and Go Test improved , this did not reach statistical significance ( P = 0.56 ; P = 0.70 , respectively ) . For most subjects sensation was unaffected by whole body vibration . Conclusion : Exercise may be beneficial to those with multiple sclerosis , but there is limited evidence that the addition of whole body vibration provides any additional improvements . Further larger scale studies into the effects of whole body vibration in people with multiple sclerosis are essential OBJECTIVE To evaluate the effects of whole-body vibration ( WBV ) training in individuals after stroke . DESIGN A double-blind r and omized controlled study with assessment s pre- and posttraining . SETTING A university hospital rehabilitation department . PARTICIPANTS Participants ( N=31 ; mean age ± SD , 62±7 y ; 6 - 101 mo poststroke ) were r and omized to an intervention group or a control group . INTERVENTIONS Supervised WBV training ( 2 sessions/wk for 6wk ; 12 repetitions of 40 - 60s WBV per session ) . The intervention group trained on a vibrating platform with a conventional amplitude ( 3.75 mm ) and the control group on a " placebo " vibrating platform ( 0.2 mm amplitude ) ; the frequency was 25Hz on both platforms . All participants and examiners were blinded to the amplitudes of the 2 platforms . MAIN OUTCOME MEASURES Primary outcome measures were isokinetic and isometric knee muscle strength ( dynamometer ) . Secondary outcome measures were balance ( Berg Balance Scale ) , muscle tone ( Modified Ashworth Scale ) , gait performance ( Timed Up & Go , comfortable gait speed , fast gait speed , and six-minute walk tests ) , and perceived participation ( Stroke Impact Scale ) . RESULTS There were no significant differences between the 2 groups after the WBV training . Significant but small improvements ( P<.05 ) in body function and gait performance were found within both groups , but the magnitude of the changes was in the range of normative variation . CONCLUSIONS Six weeks of WBV training on a vibration platform with conventional amplitude was not more efficient than a placebo vibrating platform . Therefore , the use of WBV training in individuals with chronic stroke and mild to moderate disability is not supported Objective : To investigate the effects of a single session of whole body vibration training on ankle plantarflexion spasticity and gait performance in chronic stroke patients . Design : R and omized controlled trial . Setting : Rehabilitation unit in university hospital . Participants : Thirty subjects with chronic stroke were r and omized into either a control group ( n = 15 ) or a group receiving a single session of whole body vibration ( n = 15 ) . Intervention : The intervention group was actually treated with whole body vibration while the control group was treated with placebo treatment . Main measures : The spastic changes were measured clinical ly and neurophysiologically . Subjective evaluation of ankle spasticity was performed via a visual analogue scale . Gait performances were evaluated by the timed up and go test , 10-meter walk test and cadence . A forceplate was used for measuring foot pressure . Results : The changes between whole body vibration and control groups were significantly different in Modified Ashworth Scale ( 1.33 , 95 % confidence interval ( CI ) = 1.06~1.60 ) . The Hmax/Mmax ratio ( 0.14 , 95 % CI = 0.01~0.26 ) and visual analogue scale ( 1.87 , 95 % CI = 1.15~2.58 ) were significantly decreased . Whole body vibration could significantly improve gait velocity , timed up and go test ( 6.03 , 95 % CI = 3.17~8.89 ) and 10-meter walk test ( 1.99 , 95 % CI = 0.11~3.87 ) . The uneven body weight posture on bilateral feet was also improved after vibration . Conclusion : These results suggest that a single session of whole body vibration training can reduce ankle plantarflexion spasticity in chronic stroke patients , thereby potentially increasing ambulatory capacity The effect of whole‐body vibration dosage on leg blood flow was investigated . Nine healthy young adult males completed a set of 14 r and om vibration and non‐vibration exercise bouts whilst squatting on a Galileo 900 plate . Six vibration frequencies ranging from 5 to 30 Hz ( 5 Hz increments ) were used in combination with a 2·5 mm and 4·5 mm amplitude to produce twelve 1‐min vibration bouts . Subjects also completed two 1‐min bouts where no vibration was applied . Systolic and diastolic diameters of the common femoral artery and blood cell velocity were measured by an echo Doppler ultrasound in a st and ing or rest condition prior to the bouts and during and after each bout . Repeated measures MANOVAs were used in the statistical analysis . Compared with the st and ing condition , the exercise bouts produced a four‐fold increase in mean blood cell velocity ( P<0·001 ) and a two‐fold increase in peak blood cell velocity ( P<0·001 ) . Compared to the non‐vibration bouts , frequencies of 10–30 Hz increased mean blood cell velocity by approximately 33 % ( P<0·01 ) whereas 20–30 Hz increased peak blood cell velocity by approximately 27 % ( P<0·01 ) . Amplitude was additive to frequency but only achieved significance at 30 Hz ( P<0·05 ) . Compared with the st and ing condition , squatting alone produced significant increases in mean and peak blood cell velocity ( P<0·001 ) . The results show leg blood flow increased during the squat or non‐vibration bouts and systematic ally increased with frequency in the vibration bouts BACKGROUND Whole-body vibration ( WBV ) has been used in older adults to improve bone health and neuromuscular function , and may have potential applications for stroke patients . AIM To investigate the effects of WBV on bone turnover , leg muscle strength , motor function , and spasticity among chronic stroke patients . DESIGN R and omized controlled trial ( RCT ) . SETTING Community . POPULATION Eighty-two chronic stroke patients . METHODS The experimental group underwent exercise training with WBV stimulation for a maximum of 15 minutes , 3 days per week for 8 weeks . The controls received the same exercises without WBV . Participants were evaluated for isokinetic knee muscle strength , serum levels of bone formation and resorption markers , spasticity and motor function of the paretic leg at baseline , immediately after the 8-week training period , and 1-month follow-up . RESULTS Intention-to-treat analysis revealed no significant changes in levels of bone turnover markers and motor function of the paretic leg over time in both groups . Muscle strength outcomes showed no significant group × time interaction , with similar significant improvements found in both groups . Spasticity of the paretic knee was significantly reduced in the experimental group ( P=0.005 ) , but not in controls ( P=0.465 ) . No serious adverse events were reported . CONCLUSION The WBV protocol used in this study did not induce additional effects on bone turnover , knee muscle strength and paretic leg motor function among chronic stroke patients . WBV may have potential to modulate spasticity , but this requires further investigation . CLINICAL REHABILITATION IMPACT More study on WBV is required before it can be recommended as an adjunct treatment in rehabilitation of chronic stroke patients Jacobs , PL and Burns , P. Acute enhancement of lower-extremity dynamic strength and flexibility with whole-body vibration . J Strength Cond Res 23(1 ) : 51 - 57 , 2009-The purpose of this investigation was to examine the acute effects of whole-body vibration ( WBV ) on muscular strength , flexibility , and heart rate ( HR ) . Twenty adults ( 10 men , 10 women ) untrained to WBV participated in the study . All subjects completed assessment of lower-extremity isokinetic torque , flexibility , and HR immediately before and after 6 minutes of WBV and 6 minutes of leg cycling ergometry ( CYL ) , in r and omized order . During WBV , subjects stood upright on a vibration platform for a total of 6 minutes . Vibration frequency was gradually increased during the first minute to a frequency of 26 Hz , which was maintained for the remaining 5 minutes . During CYL , power output was gradually increased to 50 W during the first minute and maintained at that power output for the remaining 5 minutes . Lower-extremity flexibility was determined using the sit- and -reach box test . Peak and average isokinetic torque of knee extension and flexion were measured by means of a motor-driven dynamometer with velocity fixed at 120 ° ·s−1 . Change scores for the outcome measures were compared between treatments using Student 's paired t-tests . Analysis revealed significantly greater HR acceleration with CYL ( 24.7 bpm ) than after WBV ( 15.8 bpm ) . The increase of sit- and -reach scores after WBV ( 4.7 cm ) was statistically greater ( p < 0.05 ) than after CYL ( 0.8 cm ) . After WBV , increases in peak and average isokinetic torque of knee extension , 7.7 % and 9.6 % , were statistically greater than after CYL ( p < 0.05 ) . Average torque of knee flexion also increased more with WBV ( + 7.8 % ) than with CYL ( −1.5 % ) ( p < 0.05 ) . The findings of this study indicate that short-term WBV st and ing elicits acute enhancements of lower-extremity muscular torque and flexibility , suggesting the application of this technology as a preparatory activity before more intense exercise CONTEXT Despite the widespread use of whole-body vibration ( WBV ) , especially in recent years , its neurophysiological mechanism is still unclear and it is yet to be determined whether acute and short-term WBV exposure produce neurogenic enhancement for agility . OBJECTIVE To compare the acute and short-term effects of WBV on the H-reflex-recruitment curve and agility . DESIGN Cross-over study . SETTING Clinical electrophysiology laboratory . PARTICIPANTS 20 nonathlete male volunteers ( mean age 24.85 ± 3.03 y ) . MAIN OUTCOME MEASURES Subjects were r and omly divided into 2 groups , H-reflex and agility . In the sham protocol , subjects stood on the turned-off vibration plate while maintaining the semisquat position , and then , after a 2-wk washout , vibration-training sessions were performed in the same position with a frequency of 30 Hz and an amplitude of 3 mm . H-reflex-recruitment curve was recorded and the agility test of a shuttle run was performed before and after the first session and also 48 h after the 11th session in both sham and vibration-training protocol s. RESULTS Acute effects of WBV training caused a significant decrease of threshold amplitude and H-max/M-max ( P = .01 and P = .04 , respectively ) . Short-term WBV training significantly decreased the threshold intensity of the soleus H-reflex-recruitment curve ( P = .01 ) and caused a decrease and increase respectively , in the threshold intensity and the area under the recruitment curve . CONCLUSIONS The results suggest an inhibitory effect of acute WBV training on the H-reflex response OBJECTIVES To investigate the effects of a 6-week whole body vibration ( WBV ) training program in patients with chronic stroke . DESIGN R and omized controlled pilot trial with 6 weeks ' follow-up . SETTING University hospital . PARTICIPANTS Adults with chronic stroke ( N=15 ) were r and omly assigned to an intervention ( n=7 ) or a control group ( n=8 ) . INTERVENTIONS Supervised , intensive WBV training . The vibration group performed a variety of static and dynamic squat exercises on a vibration platform with vibration amplitudes of 1.7 and 2.5 mm and frequencies of 35 and 40Hz . The vibration lasted 30 to 60 seconds , with 5 to 17 repetitions per exercise 3 times weekly for 6 weeks . Participants in the control group continued their usual activities and were not involved in any additional training program . MAIN OUTCOME MEASURES The primary outcome variable was the isometric and isokinetic muscle strength of the quadriceps ( isokinetic dynamometer ) . Additionally , hamstrings muscle strength , static and dynamic postural control ( dynamic posturography ) , and muscle spasticity ( Ashworth Scale ) were assessed . RESULTS Compliance with the vibration intervention was excellent , and the participants completed all 18 training sessions . Vibration frequencies of both 35 and 40Hz were well tolerated by the patients , and no adverse effects result ing from the vibration were noted . Overall , the effect of intensive WBV intervention result ed in significant between-group differences in favor of the vibration group only in isometric knee extension strength ( knee angle , 60 ° ) ( P=.022 ) after 6 weeks of intervention and in isokinetic knee extension strength ( velocity , 240 ° /s ) after a 6-week follow-up period ( P=.005 ) , both for the paretic leg . Postural control improved after 6 weeks of vibration in the intervention group when the patients had normal vision and a sway-referenced support surface ( P<.05 ) . Muscle spasticity was not affected by vibration ( P>.05 ) . CONCLUSIONS These preliminary results suggest that intensive WBV might potentially be a safe and feasible way to increase some aspect of lower limb muscle strength and postural control in adults with chronic stroke . Further studies should focus on evaluating how the training protocol should be administered to achieve the best possible outcome , as well as comparing this training protocol to other interventions |
2,160 | 24,157,952 | They concluded that ASCT done as part of frontline treatment for PTCL does not improve overall survival .
The results of the meta- analysis reported in this issue of Acta Haematologica do not support the use of ASCT as part of the initial treatment of PTCL . | A systematic review attempts to collect all empirical evidence that fits prespecified eligibility criteria in order to answer a specific research question .
Up to now , there have been five prospect i ve trials of ASCT in untreated T cell lymphomas constitute a heterogeneous group of disorders , accounting for 10–15 % of non-Hodgkin lymphomas .
The most common types in the Unites States and Europe include : peripheral T cell lymphoma ( PTCL ) not otherwise specified , angioimmunoblastic T cell lymphoma and anaplastic large cell lymphoma positive and negative for anaplastic lymphoma kinase [ 1 ] , which together account for approximately 75 % of new diagnoses .
The most commonly used treatments consist of combination chemotherapy , usually anthracycline-containing regimens , with moderate response rates and poor progression-free survival across most subtypes , with the exception of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma [ 1 , 2 ] .
Most patients are treated with paradigms primarily defined for aggressive B-cell lymphomas using regimens such as CHOP , CHOEP or EPOCH as initial therapy .
Due to the poor prognosis with conventional therapy , some groups use intensification with high-dose chemotherapy and autologous stem cell transplantation ( ASCT ) as part of the initial therapy in order to improve progression-free and overall survival .
Yet , the evidence supporting this approach is not robust . | PURPOSE Peripheral T-cell lymphomas ( PTCLs ) are a heterogeneous group of malignancies characterized by a poor prognosis . We performed a pilot study to investigate the role of reduced-intensity conditioning ( RIC ) followed by allogeneic stem-cell transplantation in relapsed or refractory PTCLs . PATIENTS AND METHODS We have conducted a phase II trial on 17 patients receiving salvage chemotherapy followed by RIC and allogeneic transplantation of hematopoietic cells . The RIC regimen consisted of thiotepa , fludarabine , and cyclophosphamide . The acute graft-versus-host disease prophylaxis consisted of cyslosporine and short course methotrexate . RESULTS Patients had a median age of 41 years ( range , 23 to 60 years ) . Two patients were primary chemorefractory , and 15 had relapsed disease ; eight patients ( 47 % ) had a disease relapse after an autologous transplantation . After a median follow-up of 28 months from the day of study entry ( range , 3 to 57 months ) , 14 of 17 patients were alive ( 12 in complete remission , one in partial remission , and one with stable disease ) , two died as a result of progressive disease , and one died as a result of sepsis concomitant to acute graft-versus-host disease . The estimated 3-year overall and progression-free survival rates were 81 % ( 95 % CI , 62 % to 100 % ) and 64 % ( 95 % CI , 39 % to 89 % ) , respectively . The estimated probability of nonrelapse mortality at 2 years was 6 % ( 95 % CI , 1 % to 17 % ) . Donor lymphocyte infusions induced a response in two patients progressing after allografting . CONCLUSION RIC followed by allogeneic stem-cell transplantation is feasible , has a low treatment-related mortality , and seems to be a promising salvage treatment for relapsed PTCL . These findings suggest that the existence of a graft-versus-T-cell lymphoma effect T-cell NHL represent 10 - 15 % of all malignant lymphomas making systematic prospect i ve clinical trials difficult . Therefore , the prognostic significance of the T-cell phenotype has been a matter of controversy in recent years . In a retrospective analysis of 681 patients ( pts ) with NHL accrued from 1992 to 1997 at a single institution , 66 patients with T-cell NHL were identified . According to the REAL classification , histologies were as follows : 28 peripheral T-cell lymphomas ( PTCL ) , 19 large cell anaplastic lymphoma ( LCAL ) , 12 precursor lymphoblastic lymphoma ( Lb ) , and seven AILD . Multiagent anthracycline containing regimens were used as initial therapy in 91 % of cases . T-cell NHL represent 9.8 % of all NHL patients at our institution accrued over a 6-year period . Overall response rate was 76 % , 21 % had progressive disease and 3 % died during first line treatment . Mean overall survival ( OS ) was 8.22 ± 0.94 years . There was a significant difference in OS between the four different histological subgroups ( log rank P = 0.0288 ) . LCAL : mean OS 11.05 ± 1.55 years ( 95 % CI 8.00 - 14.09 ) ; LB : mean OS 7.09 ± 1.40 years ( 95 % CI 4.33 - 9.84 ) ; PTCL : mean 6.62 ± 1.17 years ( 95 % CI 4.33 - 8.90 ) ; AILD : 1.54 ± 0.44 years ( 95 % CI 0.67 - 2.40 ) . OS was also significantly different for patients classified according to the International Prognostic Index (IPI)-score ( log rank P = 0.002 ) . Mean OS for patients with low risk , intermediate low risk , intermediate high risk and high risk was 10.46 ± 1.02 , 6.46 ± 1.79 , 4.50 ± 1.20 and 1.15 ± 0.46 years , respectively . Univariate analysis ( log-rank test ) for prognostic factors also revealed elevated LDH , B-symptoms and extranodal involvement as significant factors for OS . The presence of bulky disease ( > 7.5 cm ) , advanced stage III/IV and bone marrow involvement did not influence OS . In conclusion , it is evident that histological subtype and IPI-score have a strong prognostic impact on OS in pts with T-cell NHL . Thus , the distribution of risk factors in patients with T-cell NHL may be more important for OS than T-cell histology per se PURPOSE Aggressive T-cell lymphomas ( ATCLs ) represent 10 % to 15 % of non-Hodgkin 's lymphomas ( NHLs ) in adults . ATCLs show a worse prognosis than B-cell lymphomas . PATIENTS AND METHODS On behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire , we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation ( alloSCT ) . RESULTS The different diagnosis included anaplastic large-cell lymphoma ( ALCL ; n = 27 ) , peripheral T-cell lymphoma not otherwise specified ( PTCL-NOS ; n = 27 ) , angioimmunoblastic T-cell lymphoma ( AITL ; n = 11 ) , hepatosplenic gamma/delta lymphoma ( HSL ; n = 3 ) , T-cell granular lymphocytic leukemia ( T-GLL ; n = 1 ) , nasal natural killer (NK)/T-cell lymphoma ( nasal-NK/L ; n = 3 ) or non-nasal NK/T-cell lymphoma ( non-nasal-NK/L ; n = 2 ) , enteropathy-type T-cell ( n = 1 ) , and human T-lymphotropic virus (HTLV)-1 lymphoma ( n = 2 ) . Fifty-seven patients received a myeloablative conditioning regimen . Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases . Thirty-one patients were in complete remission ( CR ) at the time of alloSCT , whereas 26 were in partial response ( PR ) . Five-year toxicity-related mortality ( TRM ) incidence was 33 % ( 95 % CI , 24 % to 46 % ) . The 5-year overall survival ( OS ) and event-free survival ( EFS ) rates were 57 % ( 95 % CI , 45 % to 68 % ) and 53 % ( 95 % CI , 41 % to 64 % ) , respectively . In multivariate analysis , chemoresistant disease ( stable , refractory , or progressing disease ) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease ( aGVHD ) were the strongest adverse prognostic factors for OS ( P = .03 and .03 , respectively ) . Disease status at transplantation significantly influenced the 5-year EFS ( P = .003 ) , and an HLA-mismatched donor increased TRM ( P = .04 ) . CONCLUSION We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospect i ve clinical trials PURPOSE Systemic peripheral T-cell lymphomas ( PTCLs ) respond poorly to conventional therapy . To evaluate the efficacy of a dose-dense approach consoli date d by up-front high-dose chemotherapy ( HDT ) and autologous stem-cell transplantation ( ASCT ) in PTCL , the Nordic Lymphoma Group ( NLG ) conducted a large prospect i ve phase II study in untreated systemic PTCL . This is the final report , with a 5-year median follow-up , of the NLG-T-01 study . PATIENTS AND METHODS Treatment-naive patients with PTCL age 18 to 67 years ( median , 57 years ) were included . Anaplastic lymphoma kinase ( ALK ) -positive anaplastic large-cell lymphoma ( ALCL ) was excluded . An induction regimen of six cycles of biweekly CHOEP ( cyclophosphamide , doxorubicin , vincristine , etoposide , and prednisone ) was administered ( in patients age > 60 years , etoposide was omitted ) . If in complete or partial remission , patients proceeded to consolidation with HDT/ASCT . RESULTS Of 166 enrolled patients , 160 had histopathologically confirmed PTCL . The majority presented with advanced-stage disease , B symptoms , and elevated serum lactate dehydrogenase . A total of 115 underwent HDT/ASCT , with 90 in complete remission at 3 months post-transplantation . Early failures occurred in 26 % . Treatment-related mortality was 4 % . At 60.5 months of median follow-up , 83 patients were alive . Consoli date d 5-year overall and progression-free survival ( PFS ) were 51 % ( 95 % CI , 43 % to 59 % ) and 44 % ( 95 % CI , 36 % to 52 % ) , respectively . Best results were obtained in ALK-negative ALCL . CONCLUSION Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44 % of treatment-naive patients with PTCL . This represents an encouraging outcome , particularly considering the high median age and adverse risk profile of the study population . Therefore , dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL |
2,161 | 31,256,710 | Conclusion : Quality of clinical practice guidelines for orthotic treatment of knee osteoarthritis in the Nordic region is variable . | Background : High- quality clinical practice guidelines are necessary for effective use of re sources both at an individual patient- and national-level .
Nordic clinical practice guidelines recommendations for orthotic treatment of knee osteoarthritis vary and little is known about their quality .
Objectives : The aim of the study was to critically evaluate the quality of clinical practice guidelines in orthotic management of knee osteoarthritis in the Nordic countries . | OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis ( OA ) . DESIGN 6-month prospect i ve r and omized controlled study . PATIENTS out patients with painful medial femoro-tibial knee OA . OUTCOME MEASURES patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis . Main criterion : improvement in the patient 's assessment of activity ( defined as a reduction of 1 grade or more at month 6 compared to baseline , and no intraarticular injection or lavage during the study ) . Secondary criteria for assessment : ( a ) improvement in the patient 's assessment of activity at months 1 and 3 compared to baseline , ( b ) improvement in the WOMAC subscales at months 1 , 3 and 6 , compared to baseline ( defined as an improvement of at least 30 % , and no intraarticular injection or lavage during the study ) and ( c ) concomitant therapies ( analgesics and NSAIDs ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the two treatment groups . At months 1 , 3 and 6 the percentages of patients with improvement in assessment of disease activity , in WOMAC pain , joint stiffness , and physical functioning subscales were similar in the two groups . The number of days with NSAIDs intake during the previous 3 months was decreased at month 6 compared with baseline in the group furnished with laterally wedged insoles ( 14.1 days+/-28 vs 9.9 days+/-27 , P=0.04 , Wilcoxon paired test ) , while it remained unchanged in the other group ( 15.5 days+/-24 vs 15+/-28 , P=0.56 ) . Compliance and tolerance were satisfactory . Compliance was different between the two groups at month 6 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 87.8 % vs 74.3%;P=0.032 ) . CONCLUSION This study failed to demonstrate a relevant short-term symptomatic effect of laterally-wedged insoles in medial femoro-tibial OA . However , the decrease in NSAIDs consumption together with better compliance in the treated group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA OBJECTIVE To assess the effect of an insole with subtalar strapping on patients with medial compartment osteoarthritis ( OA ) of the knee . METHODS Novel lateral wedged insoles with elastic subtalar strapping ( the subtalar strapping support group ) and ankle supporters with a lateral wedged heel insert ( the sock-type ankle support group ) were prepared . Eighty-eight female out patients with knee OA were treated with 1 of the 2 insoles for 8 weeks . Femorotibial angle was assessed by st and ing radiographs with and without unilateral insole use for each subject . Symptoms of knee OA were evaluated according to the severity index of Lequesne et al at baseline and at the final assessment . RESULTS Participants wearing the insole with subtalar strapping ( n = 42 ) demonstrated significantly decreased femorotibial angle ( an average of change : -3.1 degrees + /- 2.5 degrees , P < 0.0001 ) , but a significant difference was not found in the sock-type ankle support group ( n = 46 ; -0.4 degrees + /- 1.1 degrees , P > 0.05 ) . In the subtalar strapping support group , pain during bed rest with full extension of the knee ( P < 0.0001 ) , pain after getting up ( P = 0.04 ) , pain on getting up from a seated position ( P = 0.021 ) , maximum distance walked ( P = 0.009 ) , and aggregate severity score ( P < 0.0001 ) were significantly improved compared with baseline . In contrast , significant symptomatic improvement was detected only in the aggregate score ( P = 0.016 ) in the sock-type ankle support group , but not in any of the 10 specific categories . CONCLUSION The lateral wedged insole with subtalar strapping induces correction of the femorotibial angle and symptomatic relief in patients with varus-deformity knee OA OBJECTIVE To assess the optimal duration of daily wear for a laterally wedged insole with subtalar strapping in subjects with medial compartment osteoarthritis of the knee ( knee OA ) . DESIGN The setting was an outpatient clinic . Eighty-one patients with knee OA were prospect ively r and omized according to birth date and to either 2 weeks of treatment with a lateral wedge with subtalar strapping for less than 5 h ( the short group ) , 5 - 10 h ( the medium group ) or greater than 10 h ( the long group ) each day , or to treatment with a subtalar strapping b and without lateral wedge ( the placebo group ) . St and ing radiographs were used to analyze the femorotibial angle for each subject , both with and without their respective orthotic device . The remission scores of Lequesne index were compared among the four groups at the conclusion . RESULTS The short ( n=21 ) , medium ( n=20 ) and long ( n=18 ) groups demonstrated a significant greater valgus correction of the femorotibial angle than the placebo group ( n=22 ) ( P<0.0001 ) . The remission score was significantly improved in the medium group compared to the placebo ( P=0.001 ) and long ( P=0.001 ) groups . CONCLUSIONS An optimal duration of insole with subtalar strapping wear for patients with varus deformity knee OA may be between 5 and 10 h each day Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 The purpose of the study was to examine the clinical efficacy of individually prescribed laterally wedged orthoses and walking shoes in the treatment of medial knee osteoarthritis using a prospect i ve , single-blind , block-r and omized controlled design . Sixty-six subjects ( 29 males , 37 females , mean age 62.4 years , mean BMI 33.0 kg/m(2 ) ) were block-r and omized to a lateral wedge ( treatment ) or neutral ( control ) orthotic group . Both groups were issued a st and ardized walking shoe for use with the orthoses . Primary outcome measures included the pain , stiffness , and functional limitations subscales of the Western Ontario and McMaster Universities index . Secondary outcome measures included the 6-minute walk distance and pain change , and stair negotiation time and pain change . A significant interaction ( p=0.039 ) favoring the treatment group was observed for pain change during the 6-minute walk . The treatment group demonstrated significant improvements at both 1 month ( p<0.001 ) and 1 year ( p<0.001 ) compared to baseline . The control group only demonstrated significant improvements at 1 year ( p=0.017 ) . No other interactions were observed . Both groups were improved at each follow-up in the WOMAC subscales for pain ( p<0.001 ) , stiffness ( p<0.001 ) , and physical function ( p<0.001 ) . Both groups also improved in 6-minute walk test distance ( p<0.001 ) , stair negotiation test time ( p=0.004 ) , and stair negotiation test pain change ( p<0.001 ) . The results suggest that both neutral and laterally wedged orthoses may be beneficial in the management of medial knee osteoarthritis when used with walking shoes . However , the addition of lateral wedging was associated with early improvements in 6-minute walk test pain change not seen in the control group OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis . METHODS STUDY DESIGN 24-month prospect i ve r and omized controlled study . PATIENTS Out patients with painful medial femoro-tibial knee osteoarthritis . OUTCOME MEASURES Patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis , with the last observation carried forward ( LOCF ) . Main symptomatic criterion : Improvement in the patient 's assessment of activity ( defined as a reduction of one grade or more at the end of the study as compared to baseline , and no intra-articular injection or lavage during the 6 months previous to the last visit ) . Secondary criteria for assessment : ( a ) Changes in the WOMAC subscales at month 24 , and ( b ) concomitant therapies ( analgesics , NSAIDs and intra-articular injections or lavages ) . Structural criterion : Joint space width ( JSW ) at the narrowest point . Non-compliance was defined as intermittent or lack of insole fitting at two consecutive visits . Compliance within groups was compared by using a life table analysis technique ( Log-Rank ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the 2 treatment groups . At year 2 , there was no statistically significant difference between the 2 groups concerning the percentages of patients with improvement in both global assessment of disease activity and in WOMAC subscales ( pain , stiffness , function ) . The number of days with NSAIDs intake was lower in the group with laterally wedged insoles than in the neutrally wedged group ( 71+/-173 days vs. 127+/-193 days , P=0.003 , Mann-Whitney test ) . The mean joint space narrowing rate did not differ between the two groups : 0.21+/-0.59 mm/year in the laterally wedged group vs 0.12+/-0.32 mm/year in the neutrally wedged group . Compliance and tolerance were satisfactory . Compliance was different between the 2 groups at month 24 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 85.8 % vs 71.9 % , P=0.023 ) . CONCLUSION This study failed to demonstrate a relevant symptomatic and /or structural effect of laterally-wedged insoles in medial femoro-tibial OA . However , the reduced NSAIDs intake and the better compliance in the treatment group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA BACKGROUND The purpose of this study was to compare a custom-made valgus-producing functional knee ( unloader ) brace , a neoprene sleeve , and medical treatment only ( control group ) with regard to their ability to improve the disease-specific quality of life and the functional status of patients who had osteoarthritis in association with a varus deformity of the knee ( varus gonarthrosis ) . METHODS The study design was a prospect i ve , parallel-group , r and omized clinical trial . Patients who had varus gonarthrosis were screened for eligibility . The criteria for exclusion included arthritides other than osteoarthritis ; an operation on the knee within the previous six months ; symptomatic disease of the hip , ankle , or foot ; a previous fracture of the tibia or femur ; morbid obesity ( a body-mass index of more than thirty-five kilograms per square meter ) ; skin disease ; peripheral vascular disease or varicose veins that would preclude use of a brace ; a severe cardiovascular deficit ; blindness ; poor English- language skills ; and an inability to apply a brace because of physical limitations such as arthritis in the h and or an inability to bend over . Treatment was assigned on the basis of a computer-generated block method of r and omization with use of sealed envelopes . The patients were stratified according to age ( less than fifty years or at least fifty years ) , deformity ( the mechanical axis in less than 5 degrees of varus or in at least 5 degrees of varus ) , and the status of the anterior cruciate ligament ( torn or intact ) . The patients were r and omly assigned to one of three treatment groups : medical treatment only ( control group ) , medical treatment and use of a neoprene sleeve , or medical treatment and use of an unloader brace . The disease-specific quality of life was measured with use of the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and the McMaster-Toronto Arthritis Patient Preference Disability Question naire ( MACTAR ) , and function was assessed with use of the six-minute walking and thirty-second stair-climbing tests . The primary outcome measure consisted of an analysis of covariance of the change in scores between the baseline and six-month evaluations . RESULTS One hundred and nineteen patients were r and omized . The control group consisted of forty patients ( thirty-one men and nine women ; mean age , 60.9 years ) ; the neoprene-sleeve group , of thirty-eight patients ( twenty-seven men and eleven women ; mean age , 58.2 years ) ; and the unloader-brace group , of forty-one patients ( twenty-eight men and thirteen women ; mean age , 59.5 years ) . Nine patients withdrew from the study . At the six-month follow-up evaluation , there was a significant improvement in the disease-specific quality of life ( p = 0.001 ) and in function ( p < or = 0.001 ) in both the neoprene-sleeve group and the unloader-brace group compared with the control group . There was a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to pain after both the six-minute walking test ( p = 0.021 ) and the thirty-second stair-climbing test ( p = 0.016 ) . There was a strong trend toward a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to the change in the WOMAC aggregate ( p = 0.062 ) and WOMAC physical function scores ( p = 0.081 ) . CONCLUSIONS The results indicate that patients who have varus gonarthrosis may benefit significantly from use of a knee brace in addition to st and ard medical treatment . The unloader brace was , on the average , more effective than the neoprene sleeve . The ideal c and i date s for each of these bracing options remain to be identified OBJECTIVE To assess the efficacy of medial-wedge insoles in valgus knee osteoarthritis ( OA ) . METHODS Thirty consecutive women with valgus-deformity knee OA > or = 8 degrees were r and omized into 2 groups : medial insole ( insoles with 8-mm medial elevation at the rearfoot [ n = 16 ] ) and neutral insole ( similar insole without elevation [ n = 14 ] ) . Both groups also wore ankle supports . A blinded examiner assessed pain on movement , at rest , and at night with a visual analog scale ( VAS ) , the Lequesne index , and Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) Index . Femorotibial , talocalcaneal , and talar tilt angles were evaluated at baseline and after 8 weeks of insole use . RESULTS Significant reductions in the medial insole group were observed for pain on movement ( mean + /- SD VAS pre- and postintervention 8.1 + /- 1.5 versus 4.2 + /- 2.4 ; P = 0.001 ) , at rest ( 5.1 + /- 2.3 versus 2.7 + /- 2.4 ; P = 0.002 ) , and at night ( 6.1 + /- 2.7 versus 3.1 + /- 2.1 ; P = 0.001 ) . In addition , a decrease in Lequesne ( 14.7 + /- 3.4 versus 9.6 + /- 3.8 ; P = 0.001 ) and WOMAC scores ( 74.1 + /- 14.2 versus 56.1 + /- 14.9 ; P = 0.001 ) was observed for the medial insole group . In the neutral insole group , a significant reduction was observed only for night pain ( mean + /- SD VAS pre- and postintervention 5.8 + /- 2.4 versus 4.6 + /- 2.4 ; P = 0.019 ) . An increase in femorotibial angle ( 169.0 + /- 3.4 versus 170.8 + /- 3.7 ; P = 0.001 ) occurred only in the medial insole group . Moreover , the difference in measured femorotibial angles pre- and postintervention was 1.84 + /- 1.42 versus -0.18 + /- 0.67 ( P < 0.001 ) for the medial and neutral insole groups . CONCLUSION The use of medial-wedge insoles was highly effective in reducing pain at rest and on movement and promoted a functional improvement of valgus knee OA In this cross-over study , we evaluated two types of knee brace commonly used in the conservative treatment of osteoarthritis of the medial compartment . Twelve patients confirmed radiologically as having unilateral osteoarthritis of the medial compartment ( Larsen grade 2 to grade 4 ) were studied . Treatment with a simple hinged brace was compared with that using a valgus corrective brace . Knee kinematics , ground reaction forces , pain and function were assessed during walking and the Hospital for Special Surgery scores were also determined . Significant improvements in pain , function , and loading and propulsive forces were seen with the valgus brace . Treatment with a simple brace showed only significant improvements in loading forces . Our findings suggest that although both braces improved confidence and function during gait , the valgus brace showed greater benefit OBJECTIVE In uncontrolled studies , a lateral-wedge insole has reduced knee pain in patients with medial knee osteoarthritis ( OA ) . The aim of this study was to test the efficacy of this simple , low-cost intervention for pain in patients with medial knee OA . METHODS We conducted a double-blind , r and omized , crossover trial design ed to detect a small effect of treatment . Participants were at least 50 years of age and had medial joint space narrowing on posteroanterior semiflexed radiographs and scores indicating moderate pain for 2 of the 5 items on the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain scale . Participants were r and omized to receive a 5 degrees lateral-wedge insole or a neutral insole for 6 weeks . Following a 4-week washout period , participants crossed over to the other treatment for 6 weeks . Knee pain , the primary outcome , was assessed by the WOMAC pain scale ( visual analog scale version ) . Secondary outcomes included the WOMAC disability subscale , overall knee pain , 50-feet walk time , chair-st and time , and use of medications for knee pain . RESULTS Ninety patients were r and omized . The mean difference in pain between the 2 treatments was 13.8 points on the WOMAC pain scale ( 95 % confidence interval -3.9 , 31.4 [ P=0.13 ] ) . We observed similar small effects for the secondary outcomes . CONCLUSION The effect of treatment with a lateral-wedge insole for knee OA was neither statistically significant nor clinical ly important OBJECTIVE To develop clinical practice guidelines for the use of foot orthotics ( FO ) in the treatment of knee and hip osteoarthritis . METHOD The SOFMER ( French Physical Medicine and Rehabilitation Society ) methodology , associating a systematic review of the literature , input from every day clinical practice and external review by a multidisciplinary expert committee , was used . The selected analysis criteria were pain , disability , medications used and X-ray evolution of osteoarthritis . The recommendations are classified according to the level of proof in Grade A , B or C according to the French National Agency for Health Accreditation and Evaluation ( NAHAE ) . RESULTS In medial knee osteoarthritis , foot pronation orthotics -- when there are no contraindications -- can be proposed for their symptomatic impact , especially in the decrease of NSAIDs consumption ( Grade B ) . To this day , there is no evidence of a structural or functional impact on osteoarthritis ( Grade B ) . Outside of this specific clinical framework , there is no vali date d indication for prescribing foot orthotics in the treatment of knee or hip OA ( Grade C ) . CONCLUSION It is necessary to have further r and omized controlled trials to better define the indication of Foot orthotics ( severity of knee OA , genu varum ) , test the efficacy of other orthoses such as cushioning FO . The long-term side effects , mainly on the external femorotibial compartment could also be assessed . A medical and economical assessment of FO prescriptions is also quite necessary OBJECTIVE To assess the effect of a lateral-wedge insole with elastic strapping of the subtalar joint on the femorotibial angle in patients with varus deformity of the knee . METHODS The efficacy of a wedged insole with subtalar straps and that of a traditional wedged insole shoe insert were compared . Sixty-six female out patients with knee osteoarthritis ( OA ) were r and omized ( according to birth date ) to be treated with either the strapped or the traditional inserted insole . St and ing radiographs with unilateral insole use were used to analyze the femorotibial angles for each patient . In both groups , the baseline and 6-month visual analog scale ( VAS ) scores for subjective knee pain and the Lequesne index scores for knee OA were compared . RESULTS The 61 patients who completed the 6-month study were evaluated . At baseline , there was no significant difference in the femorotibial angle ( P = 0.66 ) and the VAS score ( P = 0.75 ) between the 2 groups . At the 6-month assessment , the 29 subjects wearing the subtalar-strapped insole demonstrated a significantly decreased femorotibial angle ( P < 0.0001 ) and significantly improved VAS scores ( P = 0.001 ) and Lequesne index scores ( P = 0.033 ) compared with their baseline assessment s. These significant differences were not observed in the 32 subjects assigned to the traditional shoe-inserted wedged insole . CONCLUSION These results suggest that an insole with a subtalar strap maintained the valgus correction of the femorotibial angle in patients with varus knee OA for 6 months , indicating longer-term clinical improvement with the strapped insert compared with the traditional insert A study was undertaken to determine if placing shock absorbing insoles in the boots of Royal Marine recruits would attenuate the peak pressure at the foot-boot interface , when marching at 4.8 kph carrying a 32 kg ( 70 lb ) Bergen and running at 12.8 kph in loose order plus webbing weighing 10 kg ( 22 lb ) . Four types of insoles were assessed : viscoelastic polymetric insole ( Cambion(R ) ) polymetric foam insole ( PPT(R ) ) Saran insole ( military issue ) and Sorbothane(R ) . There was a fifth control condition in which no insoles were used . Pressure measurements during heel strike and forefoot loading were taken using Paratec equipment with pressure measuring insoles placed in the boots . Data were obtained from eleven subjects and indicated that all the insoles significantly ( P<0.05 ) attenuated the peak pressures generated during heel strike and forefoot loading . The performance of the four insoles in terms of peak pressure attenuation ranked in order with the best first were : Sorbothane Cambion PPT Saran . The Sorbothane insole was substantially and significantly ( P<0.05 ) better than the other insoles in terms of attenuating peak pressures during heel strike . During running , mean peak pressure at heel strike was 494 kPa in the control condition , this was reduced to 377 kPa when wearing Sorbothane insoles ( a reduction of 27 % ) . When marching the Sorbothane insoles reduced the mean peak pressure at heel strike from 395 kPa ( control ) to 303 kPa ( 23 % reduction ) . During forefoot loading the peak pressure attenuation of all four insoles was similar , although on average the Sorbothane insole performed slightly better than the others and was significantly different ( P<0 . 05 ) to the Cambion insole . Mean peak forefoot loading pressure in the control condition when running was 413 kPa , with the Sorbothane insole it was 367 kPa , during marching the respective mean peak pressures were 397 and 323 kPa . It is concluded that of the four types of insoles assessed the Sorbothane insoles attenuated the greatest amounts of the peak pressure generated at heel strike and during forefoot loading when running and marching wearing military boots OBJECTIVES To study the effectiveness of elastic sleeves in patients with knee osteoarthritis ( knee OA ) . METHOD Patients with knee OA attending the outpatient clinic of Siriraj Hospital , who met the eligibility criteria , were r and omly allocated to receive an 8-week treatment protocol . The control group received acetaminophen , non-steroidal anti-inflammatory drugs ( NSAIDs ) and education . The study group received the same treatment , in combination with a daytime elastic knee sleeve . Primary outcome variable included change in aggregated functional performance time ( AFPT ) . RESULTS In the immediate period after treatment , the study group had a mean improvement in AFPT of 1.63 seconds more than the control group ( 95 % CI : 0.21 - 3.05 , p = 0.025 ) . At the end of the 8th week , the changes of AFPT were not statistically different between the two groups . CONCLUSION This study shows small short-term beneficial effects of an elastic sleeve in patients with knee OA in cases with acute exacerbation OBJECTIVE To assess the efficacy of a lateral wedge insole with elastic strapping of the subtalar joint for conservative treatment of osteoarthritis ( OA ) of the knee . METHODS The efficacy of a novel insole with elastic subtalar strapping and a traditional shoe insert wedge insole was compared . Ninety female out patients with OA of the knee were treated with wedge insoles for 8 weeks . R and omization was performed according to birth date . St and ing radiographs with unilateral insole use were used to analyze the femorotibial and talar tilt angles for each patient with and without their respective insole . Visual analog scale ( VAS ) score for subjective knee pain at the final assessment was compared with that at baseline in both groups . RESULTS Participants wearing the elastically strapped insole ( n = 46 ) had significantly decreased femorotibial angle ( p < 0.0001 ) and talar tilt angle ( p = 0.005 ) and significantly improved VAS pain score ( p = 0.045 ) in comparison with baseline assessment s. These significant differences were not found in the group with the inserted insole ( n = 44 ) . CONCLUSION The novel strapped insole leads to valgus angulation of the talus , result ing in correction of the femorotibial angle in patients with knee OA with varus deformity , and may have a therapeutic effect similar to that of high tibial osteotomy |
2,162 | 31,581,196 | Although the difference in CO between echocardiography by different types or sites and TD was not entirely consistent , the overall effect of meta- analysis showed that no significant differences were observed between US and TD .
The techniques may be interchangeable under certain conditions | Echocardiography , as a noninvasive hemodynamic evaluation technique , is frequently used in critically ill patients .
Different opinions exist regarding whether it can be interchanged with traditional invasive means , such as the pulmonary artery catheter thermodilution ( TD ) technique .
This systematic review aim ed to analyze the consistency and interchangeability of cardiac output measurements by ultrasound ( US ) and TD . | Objective —To compare cardiac output measured by the transoesophageal Doppler and thermodilution techniques . Design — Prospect i ve direct comparison of paired measurements by both techniques in each patient . Setting —Intensive care unit in a cardiovascular centre . Patients —65 patients after open heart surgery ( mean ( SD ) age 53 ( 12 ) years ) . Interventions —Cardiac output was measured simultaneously by the transoesophageal Doppler and thermodilution techniques . Cardiac output was measured again after a mechanical intervention or volume loading . Results —The limits of agreement were −2·53 to + 0·83 1·min−1 for cardiac output measured by the Doppler and thermodilution techniques . This suggests that the Doppler method alone would not be suitable for clinical use . The second measurement of cardiac output by thermodilution was compared with cardiac output estimated from the first and second Doppler measurements and the first thermodilution measurement . The limits of agreement ( −0·55 to + 0·51 1·min−1 ) were good enough for clinical use . Conclusions —After cardiac output had been measured simultaneously by both the Doppler and thermodilution techniques , subsequent transoesophageal Doppler alone gave a clinical ly useful measurement of cardiac output OBJECTIVE To compare the haemodynamic measurements of cardiac output ( CO ) , central venous pressure ( CVP ) , pulmonary capillary wedge pressure ( Pw ) and pulmonary artery systolic pressure ( PASP ) , obtained by Swan-Ganz catheter and transthoracic echocardiography . MATERIAL AND METHODS Prospect i ve study in a Medical/Surgical Intensive Care Unit ( ICU ) . A total of 41 post liver transplant patients were enrolled . CO , CVP , Pw and PASP , were simultaneously determined by two independent observers , utilizing a Swan-Ganz catheter and transthoracic echocardiography , using equations described in the literature . A linear correlation and a Bl and -Altman analysis were performed . RESULTS A good correlation between invasive and non- invasive measurements for CO ( r=0.97 ) and CVP ( r=0.88 ) was found , but determinations of Pw ( r=0.41 ) and PASP ( r=0.18 ) did not correlate well . Bias and 95 % confidence interval for CO were negligible namely when a CO<6 l/min was considered . Pulsed-wave Doppler-echocardiography underestimates the CO when compared with thermodilution , but the 2 techniques agree on average and can be used interchangeably . CONCLUSIONS The non-invasive determination of CO in critical care post liver transplant patients correlates well with the invasive determinations . Transthoracic echocardiography was not appropriate for calculating filling parameters studied . Although the data was obtained in post liver transplant patients , they could be useful in defining the role of echocardiography in the ICU Background and objective : Intraoperative Doppler ultrasound can be used to measure cardiac output by transoesophageal echocardiography . Recently , its reliability , when compared to the thermodilution technique , has been question ed . The purpose of this study was to compare intraoperative changes in cardiac output measured by echo‐Doppler and by thermodilution in cardiac surgery . We also assessed the agreement between the techniques . Methods : Fifty cardiac surgical patients ( 38 male , 12 female , mean age of 63.4 ± 14.3 yr ) were prospect ively included after approval by the Ethics Committee of the Institution . Cardiac output was assessed by thermodilution , with 10 mL saline at 12 ° C , and simultaneously and blindly by echo‐Doppler in deep transgastric view with pulsed wave Doppler at the level of the left ventricular outflow tract . Matched thermodilution cardiac output and echo‐Doppler cardiac output measurements were taken three times at the end of expiration , both pre‐ and post‐cardiopulmonary bypass . Results : Echo‐Doppler measurements were obtained in 44 patients ( 88 % ) . In three patients , Doppler recordings could not be obtained adequately , and three developed left ventricular outflow tract obstruction after bypass . Bl and ‐Altman analysis revealed a bias of 0.015 L min−1 , with narrow limits of agreement ( −1.21 to 1.22 L min−1 ) and 29.1 % error . Echo‐Doppler was accurate ( 92 % sensitivity and 71 % specificity , P = 0.008 by receiver operating characteristic curves ) for detecting more than 10 % of change in thermodilution cardiac output . There were no complications related to the study . Conclusions : The agreement between cardiac output by echo‐Doppler and by thermodilution is clinical ly acceptable and transoesophageal echocardiography is a reliable tool to assess significant cardiac output changes in a population of selected patients OBJECTIVE To compare cardiac output ( CO ) , stroke volume ( SV ) , and cardiac index ( CI ) as estimated with a new , noninvasive Doppler device ( Ultrasonic Cardiac Output Monitor [ USCOM ] ; USCOM Ltd , Sydney , Australia ) with those measured with the bolus thermodilution ( TD ) technique . DESIGN Prospect i ve nonr and omized study . SETTING Postcardiac surgery recovery unit of a tertiary cardiac center . PARTICIPANTS Fifty patients after off-pump coronary artery bypass ( OPCAB ) surgery . MEASUREMENT AND MAIN RESULTS Both right-sided and left-sided CO were estimated with a USCOM continuous-wave ( CW ) Doppler device , and CO was determined with the bolus TD technique performed in triplicate . On comparing the right-sided CO , SV , and CI with those of TD , the mean bias was 0.03 L/min , 1.6 mL , and 0.02 L/min/m(2 ) , respectively . The comparison of left-sided CO , SV , and CI with those of TD revealed a means bias of 0.14 L/min , 1.0 mL , and 0.08 L/min/m(2 ) , respectively . CONCLUSION This study showed excellent agreement between the values for CO , SV , and CI as determined with USCOM and TD . Since there was only 1 time period for CO estimation in each patient with both methods , the stability of this correlation needs to be further investigated over time Background : The use of transesophageal echocardiography for the determination of cardiac output ( CO ) has been limited to date . We assessed the capability of aortic continuous-wave Doppler transesophageal echocardiography to determine CO ( DCO ) in a transgastric long-axis imaging plane of the heart by comparing DCO to thermodilution CO ( TCO ) . Methods : DCO was determined in 63 consecutive patients undergoing cardiac surgery . Aortic valve area was obtained from the transverse short-axis view of the valve assuming a triangular shape for the valve orifice . Stroke volume was calculated as the product of velocity – time integral and aortic valve area : stroke volume = velocity – time integral × aortic valve area . DCO was calculated off-line , by multiplying stroke volume with heart rate : DCO = stroke volume × heart rate . Results : The aortic valve orifice was easily imaged in all patients . Excellent- quality continuous-wave Doppler flow profiles were obtained in nearly all ( 62 of 63 ) . A total of 109 DCO determinations were performed . Mean DCO was 4.35 ± 1.18 1·min-1 ( range 2.02 - 7.42 1·min-1 ) , and mean TCO was 4.41 ± 1.17 1·min-1 ( range 2.24 - 8.94 1·min-1 ) . Very high correlation and agreement were found between the two methods : DCO = 0.94 × TCO + 0.19 , r=0.94 , SEE ( st and ard error of the estimate ) = 0.41 1·min-1 ; 95 % confidence interval=0.06 ± 0.83 1·min-1 . Relative changes from pre- to postbypass CO ( Δ ) also showed a strong correlation ( ΔDCO=0.93 × ΔTCO + 5.4 % , r=0.82 , SEE=17.8 % ) . For CO changes greater than 10 % , Doppler was in accordance with thermodilution in 43 of 45 measurements . DCO repeatability coefficient was 0.51 1·min-1 . Conclusions : Compared to thermodilution , continuous-wave Doppler measurements of blood flow velocity across the aortic valve in the transesophageal echocardiographic transgastric view allow accurate CO determination Objective To compare the assessment of cardiac output ( CO ) in children using the noninvasive Ultrasound Cardiac Output Monitor ( USCOM ) with the invasive pulmonary artery catheter ( PAC ) thermodilution cardiac output measurement . Design and setting Prospect i ve observational study in a tertiary center for pediatric cardiology of a university children 's hospital . Patients Twenty-four pediatric patients with congenital heart disease without shunt undergoing cardiac catheterization under general anesthesia . Measurements and results CO was measured by USCOM using a suprasternal CO Doppler probe in children undergoing cardiac catheterization . USCOM data were compared to CO simultaneously measured by PAC thermodilution technique . Measurements were repeated three times within 5 min in each patient . A mean percentage error not exceeding 30 % was defined as indicating clinical useful reliability of the USCOM . CO values measured by PAC ranged from 1.3 to 5.3 l/min ( median 3.6 l/min ) . Bias and precision were −0.13 and 1.34 l/min , respectively . The mean percentage error of CO measurement by the USCOM compared to PAC thermodilution technique was 36.4 % for USCOM . Conclusions Our preliminary data demonstrate that cardiac output measurement in children using the USCOM does not reliably represent absolute CO values as compared to PAC thermodilution . Further studies must evaluate the impact of incorporating effective aortic valve diameters on CO measurement using the USCOM BACKGROUND The USCOM ultrasonic cardiac output monitor ( USCOM Pty Ltd , Coffs Harbour , NSW , Australia ) is a non-invasive device that determines cardiac output by continuous-wave Doppler ultrasound . The aim of this study was to evaluate the accuracy of the USCOM device compared with the thermodilution technique in intensive care patients who had just undergone cardiac surgery . METHODS We conducted a prospect i ve study in the 18-bed intensive care unit of a 600-bed tertiary referral hospital . Twenty-four mechanically ventilated patients were studied immediately following cardiac surgery . We evaluated the USCOM monitor by comparing its output with paired measurements obtained by the st and ard thermodilution technique using a pulmonary artery catheter . RESULTS Forty paired measurements were obtained in 22 patients . We were unable to obtain an acceptable signal in the remaining two patients . Comparison of the two techniques showed a bias of 0.18 and limits of agreement of -1.43 to 1.78 . The agreement may not be as good between techniques at higher cardiac output values . CONCLUSIONS The USCOM monitor has a place in intensive care monitoring . It is accurate , rapid , safe , well-tolerated , non-invasive and cost-effective . The learning curve for skill acquisition is very short . However , during the learning phase the USCOM monitor measurements are rather ' operator dependent ' . Its suitability for use in high and low cardiac output states requires further validation The present study compares the cardiac output ( CO ) estimated by a new , non-invsive continuous Doppler device ( Ultrasonic cardiac output monitor-USCOM ) with that by bolus thermodilution technique ( TD ) . Thirty post off-pump coronary artery bypass graft surgery patients were studied in this prospect i ve nonr and omized study . Right heart CO estimation by USCOM and TD was performed and measured in quadruplet . A total of 120 paired observations were made . The mean CO was 4.63 and 4.76 Llmin as estimated by TD and USCOM respectively . For TD and USCOM , the CO had a mean bias ( tendency of one technique to differ from other ) of -0.13 L/min and limits of agreement ( mean bias + /- 2SD ) at -0.86 and 0.59 L/min . The study reveals very good agreement between the values of CO estimated by USCOM and TD USCOM is an ultrasound-based method which has been accepted for noninvasive hemodynamic monitoring in various clinical conditions ( USCOM , Ultrasonic cardiac output monitoring ) . The present study aim ed at comparing the accuracy of the USCOM device with that of the thermodilution technique in patients with septicemia . We conducted a prospect i ve observational study in a medical but noncardiological ICU of a university hospital . Septic adult patients ( median age 55 years , median SAPS-II-Score 43 points ) on mechanical ventilation and catecholamine support were monitored with USCOM and PiCCO ( n = 70 ) . Seventy paired left-sided CO measurements ( transaortic access = COUS-A ) were obtained . The mean COUS-A were 6.55 l/min ( ±2.19 ) versus COPiCCO 6.5 l/min ( ±2.18 ) . The correlation coefficient was r = 0.89 . Comparison by Bl and -Altman analysis revealed a bias of −0.36 l/min ( ±0.99 l/min ) leading to a mean percentage error of 29 % . USCOM is a feasible and rapid method to evaluate CO in septic patients . USCOM does reliably represent CO values as compared to the reference technique based on thermodilution ( PiCCO ) . It seems to be appropriate in situations where CO measurements are most pertinent to patient management Sixteen obstetric patients with pulmonary artery catheters were studied by two-dimensional and pulsed Doppler echocardiography to compare prospect ively pulsed Doppler- and thermodilution-derived estimations of left ventricular stroke volume and cardiac output . Systolic aortic flow velocity waveforms were obtained by pulsed Doppler ultrasound from the apical five-chamber echocardiographic window . Aortic diameters were obtained by two-dimensional echocardiography from the left parasternal long axis view . The mean ( + /- SEM ) aortic diameter averaged 2.1 + /- 0.1 cm , with a mean calculated aortic valve area of 3.6 + /- 0.2 cm2 . The mean aortic flow velocity integral was 21.8 + /- 0.8 cm . This information was used to calculate aortic stroke volume and cardiac output . Thermodilution- and Doppler-derived estimations for maternal stroke volume ( r = 0.86 ) and cardiac output ( r = 0.94 ) were significantly correlated when aortic diameter measurements based on a leading vessel edge method were used . Our findings verify the accuracy of an important noninvasive technique for quantitating maternal stroke volume and cardiac output by pulsed Doppler echocardiography . This methodology should provide an alternative approach to invasive monitoring in the study of normal and abnormal maternal circulatory hemodynamics The aim of our study was to determine the validity of cardiac output ( CO ) measurements taken with the ultrasonic cardiac output monitor ( USCOM ) by comparing to CO measured by pulmonary arterial catheter ( PAC ) thermodilution during cardiac catheterization . We enrolled thirty-one children ( < 18 years ) undergoing cardiac catheterization in this double-blinded , prospect i ve , observational study . The median CO measured by USCOM was 4.37 L/min ( IQR 3.73 , 5.60 L/min ) compared to 4.28 L/min ( IQR 3.52 , 5.26 L/min ) by PAC thermodilution . The bias ( mean difference ) between the two methods was 0.2 L/min , and the 95 % limits of agreement were −1.2 to 1.6 L/min . The mean percentage error of CO between USCOM and PAC thermodilution was 11 % . When excluding a sole outlier , the bias between the two measures decreased to 0.1 L/min ( 95 % limits of agreement −0.6 to 0.9 L/min ) , and the percentage error was reduced to 8 % . The median SVRI measured by USCOM was 22.0 Wood Units ( IQR 17.0 , 26.8 Wood Units ) compared to 22.1 Wood Units ( IQR 17.6 , 27.4 Wood Units ) by PAC thermodilution . Bias ( mean difference ) between the two methods was −0.6 Wood Units , and the 95 % limits of agreement were −8.2 to 6.9 Wood Units . We found that the estimation of CO and by extension SVRI with USCOM is reliable against pulmonary artery catheter thermodilution in children with normal cardiac anatomy . Given the noninvasive nature of USCOM , speed of measurement , and relative ease of use , it may be useful as a bedside tool for pediatric patients We evaluated the accuracy of cardiac output estimations by three transthoracic echocardiographic techniques in critically ill subjects . This study was a prospect i ve comparison study carried out in a general intensive care unit of a teaching hospital . The subjects had a broad range of diagnoses including pulmonary embolus , cardiogenic shock , septic shock , Legionnaire 's disease and perioperative myocardial infa rct ion . All patients requiring pulmonary artery catheterization underwent echocardiographic cardiac assessment with comparison of findings to those obtained by thermodilution techniques . Nineteen studies on eighteen patients were performed , with cardiac output calculated by the two-chamber Simpson 's , four-chamber Simpson 's , and left ventricular outflow tract ( LVOT ) Doppler methods . Acceptable data was obtained in those patients without mitral regurgitation . There was good correlation between the thermodilution technique and Simpson 's two-chamber method ( r=0.91 ) , but less so with the Simpson 's four-chamber method ( r=0.77 ) . All studies were included in the LVOT Doppler method with a good correlation ( r=0.94 ) . A plot of differences between methods using the Bl and and Altman statistical method indicated that only the LVOT Doppler method demonstrated acceptable agreement with a mean of 0.2 litres/minute , st and ard deviation of 0.82 litres/minute and 95 % limits of agreement of –1.5 to + 1.9 litres/minute . We concluded that the LVOT Doppler method was the only one which demonstrated acceptable agreement between the thermodilution method and echocardiographic techniques in all critically ill patients studied Purpose To compare cardiac output ( CO ) and blood volumes measured by COstatus ® ( Transonic Systems Inc. , NY , USA ) versus PiCCO ( Philips IntelliVue MP40 with PiCCO-technology module M3012A#10 , Netherl and s ) in adult ICU patients . Methods This was a prospect i ve single-center study . Each of the 30 patients studied received a 5-Fr Pulsiocath femoral arterial and a st and ard central venous catheter . Twenty ml of iced 5 % dextrose solution was injected for PiCCO measurements . For COstatus measurements , an extracorporeal arteriovenous loop , with two sensors placed on it , was connected between the Pulsiocath femoral arterial and central venous catheters . Blood was circulated through this loop at 12 ml/min for 5–8 min using a pump . Twenty ml of warm saline was injected into the venous side for measurements . For each method , three injections were averaged for comparison . Results A good agreement for measured CO ( range 3.65–16.3 l/min ) with a percentage error of 20 % was observed , with r = 0.95 , bias = −0.037 l/min . PiCCO ’s global end-diastolic volume ( GEDV ) was 2.5 times larger than the analogous COstatus ’s total end-diastolic volume ( TEDV ) [ TEDV = 0.28 × GEDV + 176 ml ] . PiCCO ’s intrathoracic blood volume ( ITBV ) was larger than the analogous COstatus ’s central blood volume ( CBV ) [ CBV = 0.73 × ( ITBV ) + 78 ml ] . Conclusions CO measured by COstatus was found to be equivalent and hence interchangeable with PiCCO in this study population . COstatus blood volumes were found to be within the expected physiological range whilst PiCCO blood volumes were significantly higher , which was also observed in other studies . Future studies using 3D echo/MRI are required to vali date these blood volumes PURPOSE Recent observations have highlighted errors in the thermodilution technique of measuring cardiac output . Thus , cardiac output measurements using transesophageal echocardiography and the Fick method were compared with simultaneous thermodilution measurements . METHODS In 13 mechanically ventilated critically ill patients , cardiac output was determined simultaneously using ( 1 ) transesophageal echocardiography ( COTEE , ( 2 ) the Fick method ( COFICK , and ( 3 ) thermodilution ( COTD immediately before and after a rapid infusion of 500 mL of saline . Left ventricular end-diastolic and end-systolic areas were measured using the transesophageal echocardiographic transgastric short axis view , and COTEE was calculated from the corresponding volumes . Absolute cardiac output values and the changes from before to after saline infusion ( delta CO ) were compared using analysis of variance , linear regression , and the Bl and and Altman method . RESULTS There were no significant differences between COTEE ( 8.0 + /- 3.4 ) , COFICK ( 8.4 + /- 3.3 ) , and COTD ( 8.3 + /- 3.0 ) or between delta COTEE , delta COFICK , and delta COTD using analysis of variance . However , correlations between COTEE and COTD ( r2 = 0.46 ; P < .00001 ) , COFICK and COTD ( r2 = 0.46 ; P < .0001 ) , and COTEE and COFICK ( r2 = 0.42 ; P < .0001 ) were only moderately good . Using the method of Bl and and Altman , the mean difference ( + /-2 st and ard deviations ) between COTEE and COTD was 0.3 + /- 4.3 L/min , between COFICK and COTD was -1.0 + /- 3.8 L/min , and between COTEE and COFICK was 0.6 + /- 5.6 L/min , whereas the difference between delta COTEE and delta COTD was 0 % + /- 26 % , between delta COFICK and delta COTD was 9 % + /- 46 % , and between delta COTEE and delta COFICK was 8 % + /- 39 % . CONCLUSIONS There are substantial differences in cardiac output as measured by these three methods , best demonstrated using the method of Bl and and Altman . The variability of cardiac output and its derivatives ( eg , oxygen delivery ) should be borne in mind when making clinical decisions on individual patients INTRODUCTION Haemodynamic monitoring is an essential element in the management of critically ill patients in the intensive care unit ( ICU ) . However , there have been increasing concerns about the clinical utility and safety profile of the invasive pulmonary artery catheter ( PAC ) . Oesophageal Doppler ( ED ) monitoring has emerged recently as a safer and less invasive tool which can be used by the intensivist to estimate cardiac output in the critically ill patient . Validation studies have thus far only been performed in surgical patients perioperatively and in mixed surgical/medical ICU patients . Currently , minimal data are available in any sizeable Asian population or in patients with severe sepsis . The assumption that these normograms and data hold true for our local medical ICU patients may not be valid due to differences in body habitus . MATERIAL S AND METHODS Our primary aim is to vali date the oesophageal Doppler as a reliable measure of cardiac index , systemic vascular resistance ( SVR ) and preload in our local Asian population of patients with severe sepsis and septic shock in the medical ICU . This was a prospect i ve pilot study on 12 consecutive mechanically ventilated patients in our medical ICU with the diagnosis of septic shock as defined by SCCM/ESICM/ACCP/ATS/SIS International Sepsis definitions Conference-Critical Care Medicine 2003 and required PAC haemodynamic monitoring as indicated by Medical Intensive Care Unit attending . RESULTS Ninety-seven paired cardiac output measurements were made . Cardiac output ranged from 2.87 to 11.0 L/ min ( calculated cardiac index ranging from 1.73 to 6.36 L/min/m2 ) when measured using the PAC with thermodilution technique and from 2.0 to 12.1 L/min ( calculated cardiac index of 1.2 to 7.2 L/min/m2 ) using the trans-oesophageal Doppler . There was moderately good correlation between CIpac and CIed ( correlation coefficient , r = 0.762 with PCA = 58 % ) . The mean bias was 0.26 L/min/m2 ( P < 0.07 ) , while the limit of agreement was + /- 1.44 L/min/m2 . CONCLUSION ED has good correlation with PAC in measuring cardiac index in Asians with septic shock but is an unreliable measure of both pre-load and SVR The aim of the study was to compare the st and ard technique of cardiac output determination by pulmonary artery catheter thermodilution ( PAC-TD ) with a noninvasive ultrasound Doppler monitor ( USCOM Pty . , Ltd. , Coffs Harbour , Australia ) in surgery for liver transplantation . We wished to determine if the degree of accuracy would allow the ultrasound cardiac output monitor ( USCOM ) to be used as an alternative monitor in a clinical setting in which wide fluctuations in cardiac output could be expected . This was a prospect i ve method comparison study , with 71 paired measurements obtained in 12 patients undergoing liver transplantation in a university teaching hospital . Bl and -Altman analysis of the 2 techniques showed a bias of 0.39 L/minute , with the USCOM cardiac output lower compared with that of PAC-TD . The bias was small and did not vary with the magnitude of the cardiac output . The 95 % limits of agreement were -1.47 and 2.25 L/minute . There was good repeatability for USCOM measurements , with a repeatability coefficient of 0.43 for USCOM versus 0.77 for PAC-TD . We conclude that USCOM is acceptable for the clinical determination of noninvasive cardiac output , particularly in situations in which tracking changes over time is more important than knowing the precise value . However , the utility of USCOM is limited by its inability to measure pulmonary artery pressure Background —Although several studies have demonstrated a good correlation between Doppler echocardiographic and invasive measurements of single hemodynamic variables , the accuracy of echocardiography in providing a comprehensive assessment in individual patients has not been vali date d. The aim of this study was to assess the accuracy and clinical applicability of Doppler echocardiography in determining the entire hemodynamic profile in stable patients with advanced systolic heart failure . Methods and Results —Doppler echocardiography and Swan-Ganz catheterization were simultaneously performed in 43 consecutive patients with advanced heart failure . Echocardiographic data required for estimation of right atrial , pulmonary artery systolic , and pulmonary capillary wedge pressures ; cardiac output ; and pulmonary vascular resistance were obtained and compared with hemodynamic data . For all variables , invasive and noninvasive hemodynamic values were highly correlated ( P<0.0001 ) , with very low bias and narrow 95 % confidence limits . In 16 patients with elevated pulmonary vascular resistance ( > 3 Wood U ) and pulmonary capillary wedge pressures ( > 20 mm Hg ) at baseline , hemodynamic and Doppler measurements were simultaneously repeated after unloading manipulations . Absolute values and changes of pulmonary vascular resistance and pulmonary capillary wedge pressures after unloading were still accurately predicted ( r=0.96 and r=0.92 , respectively ) . Conclusions —Doppler echocardiography may offer a valid alternative to invasive cardiac catheterization for the comprehensive hemodynamic assessment of patients with advanced heart failure , and it may assist in monitoring and optimization of therapy in potential heart transplant recipients OBJECTIVE The determination of basal cardiac output ( CO ) and of its variations during different therapeutic interventions liable to increase or decrease it in mechanically ventilated patients using transesophageal echocardiography ( TEE ) . DESIGN To compare CO measurements simultaneously obtained by transmitral single-plane TEE and thermodilution . SETTING Medical intensive care unit . PATIENTS Twenty-two consecutive mechanically ventilated patients hospitalized for various medical conditions were included . INTERVENTIONS The comparisons between transmitral single-plane TEE and thermodilution measurements were made at baseline and after different therapeutic interventions affecting CO ( fluids or dobutamine infusion or positive end-expiratory pressure titration ) . MEASUREMENTS Seventy-four measurements were obtained . Cardiac output using TEE was the product of the mitral valve area , the time-velocity integral of flow at the same site and the heart rate . RESULTS A significant correlation was observed between thermodilution and TEE measurements of CO ( n = 74 , r = 0.78 , p < 0.001 ) despite wide limits of agreement ( mean + /- 2SD = -0.3 + /- 3.1 l/min ) . Thermodilution and TEE CO determinations both had significant inverse correlation with the arterial-venous oxygen content difference in ten consecutive patients ( r = 0.77 , p < 0.01 and r = 0.71 , p < 0.01 , respectively ) . The correlation between variations of CO greater than 20 % obtained by thermodilution and TEE was significant ( r = 0.89 , p < 0.001 ) . The operative characteristics implied the ability of TEE to predict significant variations of thermodilution CO ( sensitivity 85 % and negative predictive values 86 % ) . Moreover , arterial-venous oxygen content difference changes of 5 % or more were better detected using TEE than thermodilution . CONCLUSIONS These results suggest that although transesophageal CO measurements can not replace thermodilution ones , the determination of CO variations obtained using TEE may be useful in the management of critically ill mechanically ventilated patients . This technique may make it possible to monitor hemodynamics during initial therapeutic interventions in those patients in whom right heart catheterization can not be performed immediately OBJECTIVE To assess the validity and potential clinical utility of cardiac output monitoring using Doppler echocardiography in patients treated with volume expansion after subarachnoid hemorrhage . DESIGN Observational study of patients in a r and omized , clinical trial . SETTING Neurologic intensive care unit . PATIENTS Simultaneous , blinded measurements of cardiac output by thermodilution and Doppler echocardiography were performed in 48 patients 1 or 2 days after aneurysmal clipping . Follow-up Doppler echocardiography was performed an average of 3.9 days later ( range 3 to 6 ) in 15 patients assigned to normovolemia and 24 patients assigned to hypervolemia . INTERVENTION Patients received supplemental 5 % albumin in order to maintain increased ( hypervolemia ) or normal ( normovolemia ) cardiac filling pressures . MEASUREMENTS AND MAIN RESULTS The overall degree of correlation between the two measures was moderate ( r = .67 , r2 = .45 , p < .0001 ) . Bias and precision calculations ( -0.75 + /- 1.34 L/min ) showed a tendency for Doppler echocardiography to underestimate thermodilution , particularly when cardiac output was very high . Although hypervolemia patients received more 5 % albumin than normovolemia patients , mean percent change in Doppler echocardiography cardiac output did not differ between the two groups . Multiple regression analysis showed that the percent change in Doppler echocardiography cardiac output correlated strongly with changes in heart rate ( p < .0001 ) , but not with daily net fluid balance or 5 % albumin administration . CONCLUSIONS Agreement was poor between Doppler echocardiography and thermodilution measurements of cardiac output , and trends reflected variations in heart rate rather than fluid status . Monitoring of cardiac output by this technique can not be recommended in patients treated with volume expansion after subarachnoid hemorrhage A newly developed transtracheal Doppler ( TTD ) computer for cardiac output determination was studied in nine patients after open heart surgery ( coronary artery bypass grafting , n = 4 ; mitral valve replacement , n = 5 ) . The measurements were compared with those simultaneously obtained by thermodilation . Doppler signals were adequate in 78 % of the patients studied . Limited correlation between both methods ( r = 0.248 ; r2 = 0.0615 ; mean of difference , 1.714 + /- 1.67 L/min ; limits of agreement , -1.6 to 5.0 L/min ) was found . The large difference in cardiac output readings between TTD and thermodilation may be due to ( a ) false angles of the ultrasound beam in relation to the aortic wall and blood flow or ( b ) misplacement of the ultrasound head and underestimation of the aortic lumen . Patients must be completely se date d and paralyzed to prohibit artifacts . Routine patient care can interfere with continuous measurements . Cardiac output determinations by TTD are limited to the period during which the trachea is intubated with the special TTD tube . We conclude that the TTD system does not offer accurate cardiac output determinations and that the routine use of this device is not practical Background : Cardiac output is a useful measure of myocardial performance . Cardiac output monitoring is frequently performed in critically ill adults to guide physicians ' treatment strategies . However , st and ard methods of determining cardiac output in children are not without risk and can be problematic secondary to their invasive nature and other technical problems . The COstatus system ( Transonic Systems , NY ) , which is based on ultrasound dilution technology , works off in situ catheters and uses an innocuous indicator to allow for routine measurements of cardiac output and blood volumes in pediatric patients . The purpose of this study was to vali date cardiac output measured by the COstatus system with those obtained by the clinical st and ard technique of pulmonary artery thermodilution . Methods : This was a prospect i ve evaluation performed at a single institution . Any child with a structurally normal heart undergoing hemodynamic evaluation in the cardiac catheterization laboratory was included . A pro grade right heart catheterization was performed , and cardiac output was first determined by using the pulmonary artery thermodilution technique . Thermodilution results were then compared with cardiac output measurements obtained using the COstatus system . The results were analyzed by st and ard correlation , Bl and -Altman , and Critchley and Critchley analyses . Results : Twenty-eight patients were evaluated with a median age of 8 yrs and a median weight of 31 kg . The mean thermodilution cardiac index = 3.18 L/min ( ± 1.35 L/min ) , and the mean COstatus system cardiac index = 3.17 L/min ( ± 1.31 L/min ) . St and ard Pearson correlation tests revealed an excellent correlation coefficient of 0.95 ( p < .0001 ) . Bl and -Altman analysis revealed good clinical agreement with a mean difference of −0.004 L/min with a precision of 0.8 L/min at 2 SD . A percentage error of 25.4 % was noticed in this study , which is less than the clinical ly acceptable limit . Conclusion : The ultrasound dilution technique of determining cardiac output using the COstatus system provides a less invasive method than the traditional pulmonary artery thermodilution for accurately determining cardiac output in children . This is the first validation of the COstatus system in pediatric patients . Further studies are required to establish its accuracy in pediatric patients with cardiac shunts and other hemodynamically unstable conditions OBJECTIVE The Sometec Dynemo-3000 system allows the permanent measurement of descending aorta diameter by an echographic ( A-scan ) device and the blood flow velocity by a pulse Doppler velocimeter . The Dynemo-3000 then furnishes a new hemodynamic parameter , i.e. , descending aortic blood flow ( ABF ) , which is a fraction of the cardiac output ( CO ) . We evaluate the ability of this system to measure the aortic diameter and to accurately detect ABF changes . DESIGN A case study prospect i ve trial . SETTING A 24-bed medical intensive care unit of a 1,100-bed university hospital . PATIENTS Twenty critically ill patients fully se date d , mechanically ventilated , and monitored by a pulmonary artery catheter . INTERVENTIONS CO values determined by conventional thermodilution method ( TD-CO ) and ABF were recorded during the study , which included two initial baseline periods , a dobutamine infusion ( 5 microg/kg/min ) interval of 30 mins , and a third baseline period . To assess the accuracy of A-scan , aortic diameter was measured by transesophageal echocardiography . The difference between echocardiography and A-scan was used to determine bias and precision for aortic diameter measurements . TD-CO and ABF variations were analyzed using Kruskal-Wallis and Wilcoxon tests . Association between TD-CO and ABF values was determined by calculating the linear correlation coefficient . The ability of ABF to detect a TD-CO > 6.0 L/min and its variations > 13 % was analyzed by determination of sensitivity , specificity , and positive ( PPV ) and negative ( NPV ) predictive values . MEASUREMENTS AND MAIN RESULTS Aortic diameter measurements by A-scan and bidimensional methods were 23.0+/-2.8 mm ( SD ) and 24.2+/-2.7 mm , respectively . Bias and precision were 1.1 mm and 1.4 mm ( 95 % confidence interval : -1.9 to 3.7 ) , respectively . During the course of dobutamine infusion , we observed a significant increase of TD-CO mean value from 6.65+/-1.53 L/min to 9.30+/-2.5 L/min ( p=.0008 ) , and a parallel and significant increase in ABF mean value from 4.34+/-1.18 L/min to 5.70+/-1.63 L/min ( p= .0029 ) . Absolute TD-CO and ABF values had a correlation coefficient of 0.80 . For detection of an increased TD-CO , PPV and NPV were 87 % and 86 % , respectively . For detection of TD-CO changes > 13 % , PPV and NPV were 80 % and 94 % , respectively . CONCLUSIONS The Dynemo-3000 system is able to display the real aortic diameter , which is one of the most important components of this noninvasive ultrasonic technique . When compared with TD-CO , the ABF determination provided by this ultrasonic device constitutes a reliable noninvasive tool for estimating CO and tracking its changes BACKGROUND The accurate measurement of Cardiac output ( CO ) is vital in guiding the treatment of critically ill patients . Invasive or minimally invasive measurement of CO is not without inherent risks to the patient . Skilled Intensive Care Unit ( ICU ) nursing staff are in an ideal position to assess changes in CO following therapeutic measures . The USCOM ( Ultrasonic Cardiac Output Monitor ) device is a non-invasive CO monitor whose clinical utility and ease of use requires testing . OBJECTIVES To compare cardiac output measurement using a non-invasive ultrasonic device ( USCOM ) operated by a non-echocardiograhically trained ICU Registered Nurse ( RN ) , with the conventional pulmonary artery catheter ( PAC ) using both thermodilution and Fick methods . DESIGN Prospect i ve observational study . SETTING AND PARTICIPANTS Between April 2006 and March 2007 , we evaluated 30 spontaneously breathing patients requiring PAC for assessment of heart failure and /or pulmonary hypertension at a tertiary level cardiothoracic hospital . METHODS SCOM CO was compared with thermodilution measurements via PAC and CO estimated using a modified Fick equation . This catheter was inserted by a medical officer , and all USCOM measurements by a senior ICU nurse . Mean values , bias and precision , and mean percentage difference between measures were determined to compare methods . The Intra-Class Correlation statistic was also used to assess agreement . The USCOM time to measure was recorded to assess the learning curve for USCOM use performed by an ICU RN and a line of best fit demonstrated to describe the operator learning curve . RESULTS In 24 of 30 ( 80 % ) patients studied , CO measures were obtained . In 6 of 30 ( 20 % ) patients , an adequate USCOM signal was not achieved . The mean difference ( + /-st and ard deviation ) between USCOM and PAC , USCOM and Fick , and Fick and PAC CO were small , -0.34+/-0.52 L/min , -0.33+/-0.90 L/min and -0.25+/-0.63 L/min respectively across a range of outputs from 2.6L/min to 7.2L/min . The percent limits of agreement ( LOA ) for all measures were -34.6 % to 17.8 % for USCOM and PAC , -49.8 % to 34.1 % for USCOM and Fick and -36.4 % to 23.7 % for PAC and Fick . Signal acquisition time reduced on average by 0.6 min per measure to less than 10 min at the end of the study . CONCLUSIONS In 80 % of our cohort , USCOM , PAC and Fick measures of CO all showed clinical ly acceptable agreement and the learning curve for operation of the non-invasive USCOM device by an ICU RN was found to be satisfactorily short . Further work is required in patients receiving positive pressure ventilation The USCOM ( Ultrasonic Cardiac Output Monitors ) device is a noninvasive cardiac output monitor , which utilises transaortic or transpulmonary Doppler flow tracing and valve area estimated using patient height to determine cardiac output . We evaluated USCOM against thermodilution cardiac outputs and transoesophageal echocardiography valve area measurements in 22 ASA PS4 cardiac surgical patients . Data collection commenced following pulmonary artery catheter insertion , with cardiac output measurements repeated after sternotomy closure . Failure to obtain transaortic Doppler readings using USCOM occurred in 5 % of planned measurements . USCOM transaortic analysis was not planned for 11 patients with known aortic disease . Bias at the aortic window ( n = 20 ) was -0.79 l/min with limits of agreement from -3.66 to 2.08 l/min . At the pulmonary window , failure to obtain Doppler readings occurred in 24 % of planned measurements . Bias at the pulmonary window ( n=36 ) was -0.17 l/min with limits of agreement from -3.30 to 2.97 l/min . The USCOM estimates of valve area based on height showed poor correlation with the echocardiographic measurements of aortic and pulmonary valves ( r=0.57 and r=0.17 , respectively ) . It was concluded that USCOM showed poor agreement with thermodilution . The estimated valve area was identified as one source of error OBJECTIVE The purpose of this study was to investigate the reliability of cardiac output ( CO ) measured by a new ultrasound dilution method ( COud ) in comparison with CO by pulmonary artery thermodilution ( COtd ) in adult patients undergoing surgery . DESIGN A prospect i ve study . SETTING A university hospital , single institutional . PARTICIPANTS Twenty-nine adult patients undergoing abdominal surgery . MEASUREMENTS AND MAIN RESULTS After approval of the institutional ethics review board , 29 adult patients were evaluated . After induction , radial and pulmonary artery catheters were inserted . A disposable extracorporeal AV loop was connected between existing arterial and central venous catheters . Reusable ultrasound sensors that measure changes in blood ultrasound velocity after dilution by isotonic saline were clamped onto the arterial and venous limbs of the loop . Ultrasound dilution ( UD ) measurements ( COstatus ; Transonic Systems , Inc , Ithaca , NY ) were obtained by injecting 30 mL of body-temperature isotonic saline into the venous limb of the AV loop . An average of 3 COud and 5 COtd was obtained for comparison . Bl and -Altman plot and correlation analysis were used for statistical comparison . A total of 142 comparison measurements were obtained . The correlation coefficient between the 2 techniques was r = 0.91 . Bl and -Altman analysis did not produce any significant bias ( bias = 0.02 , st and ard deviation = 0.56 ) . The percentage error of these data was 23.53 % . CONCLUSIONS COud measurements agreed well with COtd . The results of this study indicated that COud might be interchangeable with conventional COtd in perioperative adult patients Objective The aim of this study was to evaluate the accuracy of cardiac output measurement with transesophageal echocardiography ( TEE ) using a transgastric , pulsed Doppler method in acutely ill patients . Design Cardiac output was simultaneously measured by thermodilution ( TD ) and a transgastric , pulsed Doppler method . Setting The study was carried out in a surgical intensive care unit as part of the management protocol of the patients . Patients Thirty consecutive acutely ill patients with a Swan-Ganz catheter , mechanically ventilated , se date d and with a stable hemodynamic condition were included . Measurements Pulsed Doppler TEE was performed using a transgastric approach in order to obtain a long axis view of the left ventricle . Cardiac output was calculated from the left ventricular outflow tract diameter , the velocity time integral of the blood flow profile and heart rate . Results One patient was excluded because of the presence of aortic regurgitation and another , because of the impossibility of obtaining a transgastric view . Twenty-eight simultaneous measurements were performed in 28 patients . A clinical ly acceptable correlation and agreement were found between the two methods ( Doppler cardiac output=0.889 thermodilution cardiac output + 0.74l/min , r=0.975,p<0.0001 ) . Conclusion Transgastric pulsed Doppler measurement across the left ventricular outflow tract with TEE is a very feasible and clinical ly acceptable method for cardiac output measurement in acutely ill patients OBJECTIVE To evaluate the accuracy of measuring cardiac output ( CO ) in the early post-cardiopulmonary bypass ( CPB ) period by comparing thermodilution with Doppler methods . DESIGN Prospect i ve and blinded human trial . SETTING Academic medical center . PARTICIPANTS Thirty adult patients undergoing elective coronary artery bypass graft surgery . MEASUREMENTS AND MAIN RESULTS Thermodilution CO ( TCO ) was obtained in triplicate . Doppler CO ( DCO ) in triplicate was obtained at the left ventricular outflow tract ( LVOT ) , aortic valve ( AV ) , and right ventricular outflow tract ( RVOT ) . CO measurements were made ( 1 ) . before CPB ( baseline ) , ( 2 ) . immediately after CPB , (3).15 minutes after CPB , and ( 4 ) . 30 minutes after CPB . Before CPB , the DCO at LVOT , RVOT , and AV showed good correlations ( r = 0.87 , r = 0.88 , and r = 0.84 , respectively ) with TCO . Bias analysis showed no significant difference among TCO and 3 DCOs ( p > 0.05 each ) . Correlation between DCO and TCO decreased but remained significant after CPB ( r between 0.57 and 0.85 , p < 0.001 ) . The bias among TCO and each of the DCOs at the LVOT , RVOT , and AV increased immediately after CPB ( p < 0.01 , p < 0.01 , and p < 0.05 , respectively ) and remained significant at 15 minutes and 30 minutes post-CPB except for DCO at the AV . TCO exceeded DCO by 0.44 to 0.72 L/min immediately after CPB . The CO measured by both thermodilution and Doppler methods gradually decreased over time post-CPB . The decrease in CO was significant at 30 minutes post-CPB ( p < 0.01 ) . CONCLUSION This study adds further support that DCO is a clinical ly acceptable method to accurately assess the CO in patients even during periods of uneven regional body temperatures as may occur in the early post-CPB period The ultrasonic cardiac output monitor ( USCOM ) is a new Doppler device for noninvasive hemodynamic monitoring . The aim of this prospect i ve nonr and omized study was to test the feasibility , perioperative reliability , and clinical applicability of using USCOM as an alternative to pulmonary artery catheterization in recipients of living donor liver transplantation . Thirteen patients scheduled to receive living donor liver transplants were initially recruited . Three were subsequently excluded prior to the commencement of surgery because of technical difficulties in obtaining diagnostic- quality images with USCOM . Ten patients proceeded to be studied . Cardiac output measurements by thermodilution and USCOM were compared at 30-minute intervals throughout the procedure and at 10 specific procedural reference points during the surgery when hemodynamic changes were most likely to be observed . The data were analyzed with Lin 's concordance coefficient and Bl and -Altman analysis . Two hundred ninety paired cardiac output values were obtained from the 10 patients . The concordance between both methods was excellent in 8 patients and satisfactory in 2 . Bl and -Altman analysis of all data produced a mean bias of - 0.02 L/minute for USCOM , and the 95 % limits of agreement were -1.06 to + 1.10 L/minute . Further analysis of the 10 reference time points showed minimal bias and high levels of agreement between the methods . We conclude that USCOM provides an accurate and noninvasive method for cardiac output measurement during liver transplantation . It may therefore represent an alternative to pulmonary artery catheter placement with consequent reduction in patient 's risk and morbidity associated with catheterization . Liver Transpl 14:1029 - 1037 , 2008 . ( c ) 2008 AASLD Background Limitations in the imaging views that can be obtained with transesophageal echocardiography ( TEE ) have hindered development of a widely adopted Doppler method for cardiac output ( CO ) monitoring . The authors evaluated a CO technique that combines steerable continuous‐wave Doppler with the imaging capabilities of two‐dimensional multiplane TEE . Methods From the transverse plane transgastric , short‐axis view of the left ventricle , the imaging array was rotated to view the left ventricular outflow tract ( LVOT ) and ascending aorta . Steerable continuous‐wave Doppler was subsequently used to measure aortic blood flow velocities . Aortic valve area was determined using a triangular orifice model . Matched thermodilution and Doppler CO measurements were obtained serially during surgery . Results The left ventricular outflow tract was imaged in 32 of 33 patients ( 97 % ) . Data analysis reveal a mean difference between techniques of ‐ 0.01 l/min , and a st and ard deviation of the differences of 0.56 l/min . Multiple regression showed a correlation of r = 0.98 between intrasubject changes in CO . Multiplane TEE correctly tracked the direction of 37 of 38 serial changes in thermodilution CO but with a modest 14 % underestimation of the magnitude of these changes . Conclusions These results indicate that multiplane TEE can provide an alternative method for the intraoperative measurement of CO . The ability of the rotatable imaging array to align with the left ventricular outflow tract and the need for only minimal adjustments in probe position advance the utility of intraoperative TEE Transesophageal echocardiography permits measurement of the pulmonary artery diameter ( two-dimensional echocardiography ) and pulmonary artery blood flow velocity ( pulsed-wave Doppler ) . These measurements considered with the heart rate allow for the determination of pulmonary artery blood flow , which is equivalent to cardiac output . This study compared the precision of transesophageal Doppler-derived cardiac output ( DdCO ) with the precision of thermodilution cardiac output ( TdCO ) and examined the agreement between DdCO and TdCO in 33 cardiac surgical patients . The proximal pulmonary artery diameter was measured in triplicate during systole and end expiration , and the local blood flow velocity was recorded on video tape . The instantaneous pulmonary artery blood flow velocity ( centimeters per second ) for three r and om cardiac beats was integrated with respect to time . DdCO was calculated as the product of the flow velocity integral ( centimeters per beat ) , heart rate ( beats per min ) , and the mean cross-sectional area ( centimeters squared ) of the main pulmonary artery . At the same time that the velocity recordings were made , three serial determinations of TdCO were made by an independent observer . Pulmonary blood flow could be measured in 25 of the 33 patients . The anatomical relationship among the esophagus , the left main stem bronchus , and the pulmonary artery did not allow adequate imaging of the pulmonary artery in 8 ( 24 % ) of the patients . A total of 45 sets of triplicate measurements were made . The range of cardiac outputs encountered was 1.7 - 6.6 l.min-1 by TdCO and 1.5 - 6.9 l.min-1 by DdCO . The 95 % confidence limits for the difference between the two methods ( agreement ) was 0.030 + /- 0.987 l.min-1 . ( ABSTRACT TRUNCATED AT 250 WORDS This study was undertaken in order to eluci date the differences between various planes of measurement and Doppler techniques ( pulsed‐ vs. continuous‐wave Doppler ) across the aortic valve to estimate cardiac output . In 45 coronary artery bypass patients , cardiac output was measured each time using four different Doppler techniques ( transverse and longitudinal plane , pulsed‐ and continuous‐wave Doppler ) and compared with the thermodilution technique . Measurements were performed after induction of anaesthesia and shortly after arrival in the intensive care unit . Optimal imaging was obtained in 91 % of the patients , in whom a total of 82 measurements of cardiac output were performed . The respective mean ( SD ) areas of the aortic valve were 3.77 ( 0.71 ) cm2 in the transverse plane and 3.86 ( 0.89 ) cm2 in the longitudinal plane . A correlation of 0.87 was found between pulsed‐wave Doppler cardiac output and the thermodilution technique in either transverse or longitudinal plane . Correlation coefficients of 0.82 and 0.84 were found between thermodilution cardiac output and transverse and longitudinal continuous‐wave Doppler cardiac output , respectively . Although thermodilution cardiac output is a widely accepted clinical st and ard , transoesophageal Doppler echocardiography across the aortic valve offers adequate estimations of cardiac output . In particular , pulsed‐wave Doppler cardiac output in both the transverse and longitudinal plane provides useful data A non-invasive method for measuring cardiac output utilizing M-mode echography and pulsed Doppler ultrasound is described . Measurements were obtained in 26 of 29 r and omly selected , mechanically ventilated patients . These values were compared with simultaneously measured cardiac outputs by thermodilution . There was a statistically significant linear relationship between Cardiac Output measured by Doppler ( DCO ) and Thermodilution ( TDCO ) : DCO = 0.86 TDCO + 0.29 l/min ( r = 0.96 , n = 26 , SEE = 0.45 l/min ) over the range of 1.75 - 8.5 l/min . DCO had the additional advantage of measuring peak flow velocity and maximal blood flow acceleration during early systole , indices of left ventricular pumping ability . Ultrasonic monitoring of cardiac output may be an important supplement to invasive methods in critical care BACKGROUND Three-dimensional transoesophageal echocardiography ( 3D-TOE ) is a new noninvasive tool for quantitative assessment of left ventricular ( LV ) volumes and ejection fraction . AIM The objective of this pilot study was to evaluate the feasibility and accuracy of 3D-TOE for the estimation of cardiac output ( CO ) , using transpulmonary thermodilution with the Pulse index Contour Continuous Cardiac Output ( PiCCO ) system as the reference method , in intensive care unit ( ICU ) patients . METHODS Fifteen ICU patients on mechanical ventilation prospect ively underwent PiCCO catheter implantation and 3D-TOE . 3D-TOE LV end-diastolic and end-systolic volumes were determined using semi-automated software . CO was calculated as the product of LV stroke volume ( end-diastolic volume-end-systolic volume ) multiplied by heart rate . CO was also determined invasively by transpulmonary thermodilution as the reference method . RESULTS Among 30 haemodynamic evaluations , 29 ( 97 % ) LV 3D-TOE data sets were suitable for CO calculation . The mean 3D-TOE image acquisition and post-processing times were 46 and 155seconds , respectively . There was a correlation ( r=0.78 ; P<0.0001 ) between PiCCO and 3D-TOE CO . Compared with PiCCO , the 3D-TOE CO mean bias was 0.38L/min , with limits of agreement of -1.97 to 2.74L/min . CONCLUSIONS Noninvasive estimation of CO by 3D-TOE is feasible in ICU patients . This new semi-automated modality is an additional promising tool for noninvasive haemodynamic assessment of ICU patients . However , the wide limits of agreement with thermodilution observed in this pilot study require further investigation in larger cohorts of patients Objective : To vali date cardiac output measurements by ultrasound dilution technology ( COstatus monitor ) against those obtained by a transit-time ultrasound technology with a perivascular flow probe and to investigate ultrasound dilution ability to estimate pulmonary to systemic blood flow ratio in children . Design : Prospect i ve observational clinical trial . Setting : Pediatric cardiac operating theater in a university hospital . Material and Methods : In 21 children ( 6.1 ± 2.6 kg , mean ± SD ) undergoing heart surgery , cardiac output was simultaneously recorded by ultrasound dilution ( extracorporeal arteriovenous loop connected to existing arterial and central venous catheters ) and a transit-time ultrasound probe applied to the ascending aorta , and when possible , the main pulmonary artery . The pulmonary to systemic blood flow ratio estimated from ultrasound dilution curve analysis was compared with that estimated from transit-time ultrasound technology . Results : Bl and -Altman analysis of the whole cohort ( 90 pairs , before and after surgery ) showed a bias between transit-time ultrasound ( 1.01 ± 0.47 L/min ) and ultrasound dilution technology ( 1.03 ± 0.51 L/min ) of –0.02 L/min , limits of agreement –0.3 to 0.3 L/min , and percentage error of 31 % . In children with no residual shunts , the bias was –0.04 L/min , limits of agreement –0.28 to 0.2 L/min , and percentage error 19 % . The pooled co efficient of variation was for the whole cohort 3.5 % ( transit-time ultrasound ) and 6.3 % ( ultrasound dilution ) , and in children without shunt , it was 2.9 % ( transit-time ultrasound ) and 4 % ( ultrasound dilution ) , respectively . Ultrasound dilution identified the presence of shunts ( pulmonary to systemic blood flow ≠ 1 ) with a sensitivity of 100 % and a specificity of 92 % . Mean pulmonary to systemic blood flow ratio by transit-time ultrasound was 2.6 ± 1.0 and by ultrasound dilution 2.2 ± 0.7 ( not significant ) . Conclusion : The COstatus monitor is a reliable technique to measure cardiac output in children with high sensitivity and specificity for detecting the presence of shunts OBJECTIVE This study investigated the accuracy of arterial waveform analysis estimations of cardiac output ( COAW ) and the efficacy of calibrations involving transesophageal echocardiography with continuous cardiac output values obtained using a pulmonary artery catheter . DESIGN Prospect i ve cohort study . SETTING University hospital operating room . PARTICIPANTS Twelve patients undergoing aortic valve replacement for aortic stenosis . INTERVENTIONS A pulmonary artery catheter was placed in each patient , and continuous cardiac output was determined using thermodilution principles . LiDCOrapid and transesophageal echocardiography were used to measure COAW and to perform the calibration , respectively . MEASUREMENTS AND MAIN RESULTS Simultaneous recording of continuous cardiac output and COAW values were performed every 20 minutes , after inducing anesthesia . COAW was calibrated using transesophageal echocardiography ( COAW-cal ) before and after initiating cardiopulmonary bypass ( CPB ) ; the COAW and COAW-cal were recorded concurrently using a LiDCOrapid monitor . For the pre-CPB data set ( 34 data pairs ) , the mean bias and percentage error were , respectively , 0.10 L/min and 34 % for COAW versus continuous cardiac output and -0.098 L/min and 27 % for COAW-cal versus continuous cardiac output . Similarly , for the post-CPB ( 45 data pairs ) , the mean bias and percentage error were , respectively , 0.75 L/min and 34 % for COAW and 0.059 L/min and 26 % for COAW-cal . A 4-quadrant plot demonstrated an acceptable pre-CPB concordance rate of 93.3 % for COAW and 93.8 % for COAW-cal . CONCLUSION COAW measurements , using LiDCOrapid , have acceptable trending ability pre-CPB . The determination of cardiac output variations , using transesophageal echocardiography , is useful for managing patients undergoing aortic valve replacement for aortic stenosis |
2,163 | 23,889,316 | Strong evidence support improvements of aerobic exercise performance and VO2max following SIT .
Solid evidence support peripheral adaptations known to increase the oxidative potential of the muscle following SIT , whereas evidence regarding central adaptations was limited and equivocal .
Some evidence indicated changes in substrate oxidation at rest and during exercise as well as improved glycemic control and insulin sensitivity following SIT .
In conclusion , strong evidence support improvement of aerobic exercise performance and VO2max following SIT , which coincides with peripheral muscular adaptations . | Recently , several studies have examined whether low-volume sprint interval training ( SIT ) may improve aerobic and metabolic function .
The objective of this study was to systematic ally review the existing literature regarding the aerobic and metabolic effects of SIT in healthy sedentary or recreationally active adults . | The aim of this study was to investigate the effects of very high intensity sprint interval training ( SIT ) on metabolic and vascular risk factors in overweight/obese sedentary men . Ten men ( age , 32.1 ± 8.7 years ; body mass index , 31.0 ± 3.7 kg m(-2 ) ) participated . After baseline metabolic , anthropometric , and fitness measurements , participants completed a 2-week SIT intervention , comprising 6 sessions of 4 to 6 repeats of 30-second Wingate anaerobic sprints on an electromagnetically braked cycle ergometer , with 4.5-minute recovery between each repetition . Metabolic , anthropometric , and fitness assessment s were repeated post-intervention . Both maximal oxygen uptake ( 2.98 ± 0.15 vs 3.23 ± 0.14 L min(-1 ) , P = .013 ) and mean Wingate power ( 579 ± 24 vs 600 ± 19 W , P = .040 ) significantly increased after 2 weeks of SIT . Insulin sensitivity index ( 5.35 ± 0.72 vs 4.34 ± 0.72 , P = .027 ) and resting fat oxidation rate in the fasted state ( 0.13 ± 0.01 vs 0.11 ± 0.01 g min(-1 ) , P = .019 ) were significantly higher and systolic blood pressure ( 121 ± 3 vs 127 ± 3 mm Hg , P = .020 ) and resting carbohydrate oxidation in the fasted state ( 0.03 ± 0.01 vs 0.08 ± 0.02 g min(-1 ) , P = .037 ) were significantly lower 24 hours post-intervention compared with baseline , but these changes were no longer significant 72 hours post-intervention . Significant decreases in waist ( 98.9 ± 3.1 vs 101.3 ± 2.7 cm , P = .004 ) and hip ( 109.8 ± 2.2 vs 110.9 ± 2.2 cm , P = .017 ) circumferences compared with baseline were also observed after the intervention . Thus , 2 weeks of SIT substantially improved a number of metabolic and vascular risk factors in overweight/obese sedentary men , highlighting the potential for this to provide an alternative exercise model for the improvement of vascular and metabolic health in this population Low-volume sprint interval training ( SIT ) , or repeated sessions of brief , intense intermittent exercise , elicits metabolic adaptations that resemble traditional high-volume endurance training ( ET ) . The effects of these different forms of exercise training on vascular structure and function remain largely unexplored . To test the hypothesis that SIT and ET would similarly improve peripheral artery distensibility and endothelial function and central artery distensibility , we recruited 20 healthy untrained subjects ( age : 23.3 + /- 2.8 yr ) and had them perform 6 wk of SIT or ET ( n = 5 men and 5 women per group ) . The SIT group completed four to six 30-s " all-out " Wingate tests separated by 4.5 min of recovery 3 days/wk . The ET group completed 40 - 60 min of cycling at 65 % of their peak oxygen uptake ( Vo2peak ) 5 days/wk . Popliteal endothelial function , both relative and normalized to shear stimulus , was improved after training in both groups ( main effect for time , P < 0.05 ) . Carotid artery distensibility was not statistically altered by training ( P = 0.29 ) in either group ; however , popliteal artery distensibility was improved in both groups to the same degree ( main effect , P < 0.05 ) . We conclude that SIT is a time-efficient strategy to elicit improvements in peripheral vascular structure and function that are comparable to ET . However , alterations in central artery distensibility may require a longer training stimuli and /or greater initial vascular stiffness than observed in this group of healthy subjects Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance . Twelve healthy men ( 22 + /- 2 yr of age ) underwent intense interval training on a cycle ergometer for 7 wk . Training consisted of 30-s maximum sprint efforts ( Wingate protocol ) interspersed by 2 - 4 min of recovery , performed three times per week . The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7 . Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption ( VO2 max ) were measured before and after the training program . Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase , total glycogen phosphorylase , phosphofructokinase , lactate dehydrogenase , citrate synthase , succinate dehydrogenase , malate dehydrogenase , and 3-hydroxyacyl-CoA dehydrogenase . The training program result ed in significant increases in peak power output , total work over 30 s , and VO2 max . Maximal enzyme activity of hexokinase , phosphofructokinase , citrate synthase , succinate dehydrogenase , and malate dehydrogenase was also significantly ( P < 0.05 ) higher after training . It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity , maximum short-term power output , and VO2 max Adaptations in fat and carbohydrates metabolism after a prolonged endurance training program were examined using stable isotope tracers of glucose ( [6,6 - 2H2]glucose ) , glycerol ( [2H5]glycerol ) , and palmitate ( [2H2]palmitate ) . Active , but untrained , males exercised on a cycle for 2 h/day [ 60 % pretraining peak O2 consumption ( VO2peak ) = 44.3 + /- 2.4 ml.kg-1.min-1 ] for a total of 31 days . Three cycle tests ( 90 min at 60 % pretraining VO2peak ) were administered before training ( PRE ) and after 5 ( 5D ) and 31 ( 31D ) days of training . Exercise increased the rate of glucose production ( Ra ) and utilization ( Rd ) as well as the rate of lipolysis ( glycerol Ra ) and free fatty acid turnover ( FFARa/Rd ) . At 5D , training induced a 10 % ( P < 0.05 ) increase in total fat oxidation because of an increase in intramuscular triglyceride oxidation ( + 63 % , P < 0.05 ) and a decreased glycogen oxidation ( -16 % , P < 0.05 ) . At 31D , total fat oxidation during exercise increased a further 58 % ( P < 0.01 ) . The pattern of fat utilization during exercise at 31D showed a reduced reliance on plasma FFA oxidation ( FFA Rd ) and a greater dependence on oxidation of intramuscular triglyceride , which increased more than twofold ( P < 0.001 ) . In addition , glucose Ra and Rd were reduced at all time points during exercise at 31D compared with PRE and 5D . We conclude that long-term training induces a progressive increase in fat utilization mediated by a greater oxidation of fats from intramuscular sources and a reduction in glucose oxidation . Initial changes are present as early as 5D and occur before increases in muscle maximal mitochondrial enzyme activity UNLABELLED Repeated maximal-intensity short- duration exercise ( sprint interval training , SIT ) can produce muscle adaptations similar to endurance training ( ET ) despite a much reduced training volume . However , most SIT data use cycling , and little is known about its effects on body composition or maximal cardiac output ( Qmax ) . PURPOSE The purpose of this study was to assess body composition , 2000-m run time trial , VO(2max ) , and Q(max ) effects of run SIT versus ET . METHODS Men and women ( n = 10 per group ; mean ± SD : age = 24 ± 3 yr ) trained three times per week for 6 wk with SIT , 30-s all-out run sprints ( manually driven treadmill ) , four to six bouts per session , 4-min recovery per bout , versus ET , 65 % VO(2max ) for 30 to 60 min·d(-1 ) . RESULTS Training improved ( P < 0.05 ) body composition , 2000-m run time trial performance , and VO(2max ) in both groups . Fat mass decreased 12.4 % with SIT ( mean ± SEM ; 13.7 ± 1.6 to 12.0 ± 1.6 kg ) and 5.8 % with ET ( 13.9 ± 1.7 to 13.1 ± 1.6 kg ) . Lean mass increased 1 % in both groups . Time trial performance improved 4.6 % with SIT ( -25.6 ± 8.1 s ) and 5.9 % with ET ( -31.9 ± 6.3 s ) . VO(2max ) increased 11.5 % with SIT ( 46.8 ± 1.6 to 52.2 ± 2.0 mL·kg·(-1)·min(-1 ) ) and 12.5 % with ET ( 44.0 ± 2.0 to 49.5 ± 2.6 mL·kg·(-1)·min(-1 ) ) . None of these improvements differed between groups . In contrast , Q(max ) increased by 9.5 % with ET only ( 22.2 ± 2.0 to 24.3 ± 1.6 L·min(-1 ) ) . CONCLUSIONS Despite a fraction of the time commitment , run SIT induces similar body composition , VO(2max ) , and performance adaptations as ET , but with no effect on Q(max ) . These data suggest that adaptations with ET are of central origin primarily , whereas those with SIT are more Parra et al. ( Acta Physiol . Sc and 169 : 157 - 165 , 2000 ) showed that 2 wk of daily sprint interval training ( SIT ) increased citrate synthase ( CS ) maximal activity but did not change " anaerobic " work capacity , possibly because of chronic fatigue induced by daily training . The effect of fewer SIT sessions on muscle oxidative potential is unknown , and aside from changes in peak oxygen uptake ( Vo(2 peak ) ) , no study has examined the effect of SIT on " aerobic " exercise capacity . We tested the hypothesis that six sessions of SIT , performed over 2 wk with 1 - 2 days rest between sessions to promote recovery , would increase CS maximal activity and endurance capacity during cycling at approximately 80 % Vo(2 peak ) . Eight recreationally active subjects [ age = 22 + /- 1 yr ; Vo(2 peak ) = 45 + /- 3 ml.kg(-1).min(-1 ) ( mean + /- SE ) ] were studied before and 3 days after SIT . Each training session consisted of four to seven " all-out " 30-s Wingate tests with 4 min of recovery . After SIT , CS maximal activity increased by 38 % ( 5.5 + /- 1.0 vs. 4.0 + /- 0.7 mmol.kg protein(-1).h(-1 ) ) and resting muscle glycogen content increased by 26 % ( 614 + /- 39 vs. 489 + /- 57 mmol/kg dry wt ) ( both P < 0.05 ) . Most strikingly , cycle endurance capacity increased by 100 % after SIT ( 51 + /- 11 vs. 26 + /- 5 min ; P < 0.05 ) , despite no change in Vo(2 peak ) . The coefficient of variation for the cycle test was 12.0 % , and a control group ( n = 8) showed no change in performance when tested approximately 2 wk apart without SIT . We conclude that short sprint interval training ( approximately 15 min of intense exercise over 2 wk ) increased muscle oxidative potential and doubled endurance capacity during intense aerobic cycling in recreationally active individuals The insulin resistance of skeletal muscle in glucose-tolerant obese individuals is associated with reduced activity of oxidative enzymes and a disproportionate increase in activity of glycolytic enzymes . Because non-insulin-dependent diabetes mellitus ( NIDDM ) is a disorder characterized by even more severe insulin resistance of skeletal muscle and because many individuals with NIDDM are obese , the present study was undertaken to examine whether decreased oxidative and increased glycolytic enzyme activities are also present in NIDDM . Percutaneous biopsy of vatus lateralis muscle was obtained in eight lean ( L ) and eight obese ( O ) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [ phosphofructokinase , glyceraldehyde phosphate dehydrogenase , hexokinase ( HK ) ] and oxidative pathways [ citrate synthase ( CS ) , cytochrome-c oxidase ] , as well as for a glycogenolytic enzyme ( glycogen phosphorylase ) and a marker of anaerobic ATP re synthesis ( creatine kinase ) . Insulin sensitivity was measured by using the euglycemic clamp technique . Activity for glycolytic enzymes ( phosphofructokinase , glyceraldehye phosphate dehydrogenase , HK ) was highest in subjects with subjects with NIDDM , following the order of NIDDM > O > L , whereas maximum velocity for oxidative enzymes ( CS , cytochrome-c oxidase ) was lowest in subjects with NIDDM . The ratio between glycolytic and oxidative enzyme activities within skeletal muscle correlated negatively with insulin sensitivity . The HK/CS ratio had the strongest correlation ( r = -0.60 , P < 0.01 ) with insulin sensitivity . In summary , an imbalance between glycolytic and oxidative enzyme capacities is present in NIDDM subjects and is more severe than in obese or lean glucose-tolerant subjects . The altered ratio between glycolytic and oxidative enzyme activities found in skeletal muscle of individuals with NIDDM suggests that a dysregulation between mitochondrial oxidative capacity and capacity for glycolysis is an important component of the expression of insulin resistance Very high-intensity , low-volume , sprint interval training ( SIT ) increases muscle oxidative capacity and may increase maximal oxygen uptake ( $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ ) , but whether circulatory function is improved , and whether SIT is feasible in overweight/obese women is unknown . To examine the effects of SIT on $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ and circulatory function in sedentary , overweight/obese women . Twenty-eight women with BMI > 25 were r and omly assigned to SIT or control ( CON ) groups . One week before pre-testing , subjects were familarized to $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ testing and the workload that elicited 50 % $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ was calculated . Pre- and post-intervention , circulatory function was measured at 50 % of the pre-intervention $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ , and a GXT was performed to determine $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ . During the intervention , SIT training was given for 3 days/week for 4 weeks . Training consisted of 4–7 , 30-s sprints on a stationary cycle ( 5 % body mass as resistance ) with 4 min active recovery between sprints . CON maintained baseline physical activity . Post-intervention , heart rate ( HR ) was significantly lower and stroke volume ( SV ) significantly higher in SIT ( −8.1 and 11.4 % , respectively ; P < 0.05 ) during cycling at 50 % $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ ; changes in CON were not significant ( 3 and −4 % , respectively ) . Changes in cardiac output ( $ $ { \dot{\text{Q } } } $ $ ) and arteriovenous oxygen content difference [ ( a − v)O2 diff ] were not significantly different for SIT or CON . The increase in $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ by SIT was significantly greater than by CON ( 12 vs. −1 % ) . Changes by SIT and CON in HRmax ( −1 vs. −1 % ) were not significantly different . Four weeks of SIT improve circulatory function during submaximal exercise and increases $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ in sedentary , overweight/obese women The purpose of this study was to identify potential gender discrepancies in adaptation to low-volume high-intensity interval training ( HIT ) . Active , young men ( n = 11 , age = 25.3 ± 5.5 years ) and women ( n = 9 , age = 25.2 ± 3.1 years ) matched for age , physical activity , and VO2max completed six sessions of HIT separated by 48 h over a 2–3 week period . Subjects completed four Wingate tests on days 1 and 2 , five on days 3 and 4 , and six on days 5 and 6 . A control group of five men and four women ( age = 22.8 ± 2.8 years ) completed all testing , but did not perform HIT . Changes in VO2max , oxygen ( O2 ) pulse , peak/mean power output , fatiguability , substrate oxidation , and voluntary force production of the knee flexors and extensors were examined pre- and post-training with repeated measures ANOVA , with gender and group as between-subjects variables . Results showed significant ( p < 0.05 ) improvements in VCO2max and peak/mean power output in response to HIT , as well as reduced respiratory exchange ratio and heart rate during submaximal exercise . The magnitude of change in VO2max ( 5.9 vs. 6.8 % ) , power output ( 10.4–14.9 % vs. 9.1–10.9 % ) , and substrate oxidation was similar ( p > 0.05 ) between men and women . Data show that adaptations to 6 days of low-volume HIT are similar in men and women matched for VO2max and physical activity Sprint interval training ( SIT ) and traditional endurance training elicit similar physiological adaptations . From the perspective of metabolic function , superior glucose regulation is a common characteristic of endurance-trained adults . Accordingly , we have investigated the hypothesis that short-term SIT will increase insulin sensitivity in sedentary/recreationally active humans . Thirty one healthy adults were r and omly assigned to one of three conditions : ( 1 ) SIT ( n = 12 ) : six sessions of repeated ( 4 - 7 ) 30 s bouts of very high-intensity cycle ergometer exercise over 14 days ; ( 2 ) sedentary control ( n = 10 ) ; ( 3 ) single-bout SIT ( n = 9 ) : one session of 4 x 30 s cycle ergometer sprints . Insulin sensitivity was determined ( hyperinsulinaemic euglycaemic clamp ) prior to and 72 h following each intervention . Compared with baseline , and sedentary and single-bout controls , SIT increased insulin sensitivity ( glucose infusion rate : 6.3 + /- 0.6 vs. 8.0 + /- 0.8 mg kg(1 ) min(1 ) ; mean + /- s.e.m . ; P = 0.04 ) . In a separate study , we investigated the effect of SIT on the thermogenic response to beta-adrenergic receptor ( beta-AR ) stimulation , an important determinant of energy balance . Compared with baseline , and sedentary and single-bout control groups , SIT did not affect resting energy expenditure ( EE : ventilated hood technique ; 6274 + /- 226 vs. 6079 + /- 297 kJ day(1 ) ; P = 0.51 ) or the thermogenic response to isoproterenol ( 6 , 12 and 24 ng ( kg fat-free mass)(1 ) min(1 ) : % EE 11 + /- 2 , 14 + /- 3 , 23 + /- 2 vs. 11 + /- 1 , 16 + /- 2 , 25 + /- 3 ; P = 0.79 ) . Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose , insulin , adiponectin , pigment epithelial-derived factor , non-esterified fatty acids or noradrenaline ( all P > 0.05 ) . Sixteen minutes of high-intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to beta-AR stimulation |
2,164 | 22,860,015 | Differences were not seen with psychotherapy compared to antidepressants , alternative therapies or active intervention controls .
CONCLUSIONS In conclusion , the combination of psychotherapy and antidepressants for depression may provide a slight advantage whereas antidepressants alone and psychotherapy alone are not significantly different from alternative therapies or active intervention controls .
These data suggest that type of treatment offered is less important than getting depressed patients involved in an active therapeutic program . | BACKGROUND Although previous meta-analyses have examined effects of antidepressants , psychotherapy , and alternative therapies for depression , the efficacy of these treatments alone and in combination has not been systematic ally compared .
We hypothesized that the differences between approved depression treatments and controls would be small . | OBJECTIVE The authors examined which , if any , research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials . METHOD Clinical trial data were review ed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000 . From the antidepressant research programs on these medications , 52 clinical trials were included in the study . The authors evaluated trial design features , patient characteristics , and difference in response between placebo and antidepressant . RESULTS Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants . The severity of depressive symptoms before patient r and omization , the dosing schedule ( flexible versus fixed ) , the number of treatment arms , and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo . The duration of the antidepressant trial , number of patients per treatment arm , number of sites , and mean age of the patients were similar in successful trials ( with a greater antidepressant-placebo difference ) and less successful trials ( with a smaller antidepressant-placebo difference ) . CONCLUSIONS These findings may help in the design of future antidepressant trials Pharmacotherapy and psychotherapy are generally effective treatments for major depressive disorder ( MDD ) ; however , research suggests that patient preferences may influence outcomes . We examined the effects of treatment preference on attrition , therapeutic alliance , and change in depressive severity in a longitudinal r and omized clinical trial comparing pharmacotherapy and psychotherapy . Prior to r and omization , 106 individuals with MDD reported whether they preferred psychotherapy , antidepressant medication , or had no preference . A mismatch between preferred and actual treatment was associated with greater likelihood of attrition , fewer expected visits attended , and a less positive working alliance at session 2 . There was a significant indirect effect of preference match on depression outcomes , primarily via effects of attendance . These findings highlight the importance of addressing patient preferences , particularly in regard to patient engagement , in the treatment of MDD OBJECTIVE The authors examined the association of treatment preferences with treatment initiation , adherence , and clinical outcome among nonsenior adult and senior primary care patients with depression . METHODS Sixty primary care participants meeting DSM-IV criteria for major depression were r and omly assigned to receive treatment congruent or incongruent with their primary stated preference . Participants received either 20 weeks of escitalopram , with monitoring by a care manager , or 12 weekly sessions of interpersonal psychotherapy followed by two monthly booster sessions . Adherence to treatment and depression severity were reassessed at weeks 4 , 8 , 12 , and 24 . RESULTS Participants expressed stronger preferences for psychotherapy than for antidepressant medication . Preference strength was a more sensitive measure of outcome than was congruence versus incongruence of preference with the assigned treatment . Across age groups , preference strength was significantly associated with treatment initiation and 12-week adherence rate but not with depression severity or remission . CONCLUSIONS A continuous measure of preference strength may be a more useful measure in clinical practice than preferences per se . Future research should focus on whether and how greater facilitation of the treatment decision-making process between patient and clinician influences clinical outcome Rejection of catheters is generally thought to be due to patients pulling out their catheters , but we found circumstantial evidence for this in only one third of cases . Some catheters with smaller balloons drop out spontaneously , perhaps owing to laxity of the pelvic floor or urethral dilatation caused by repeated catheterisation , and others are expelled forcibly , presumably owing to uninhibited contractions of the bladder . Urinary catheters may therefore drop out , be pushed out , or be pulled out . The life expectancy of catheters in this group of patients suggests the type of catheter that should be used . We recommend cheaper latex catheters and think that expensive " long life " silicon catheters are inappropriate in most long stay patients . Rejection of catheters is common in poorly mobile old people with cognitive impairment . It is associated with urethral trauma and may result in septicaemia . Long term catheterisation should therefore be considered only when other methods to promote continence and provide comfort have failed.3 Further work is needed to determine why some patients pull out their catheters and whether bladder stabilising drugs might reduce episodes of spontaneous rejection of catheters Background : Clinicians and research ers have question ed whether participants in r and omized control trials ( RCTs ) are representative of patients in the broader clinical population . Method : We compared the demographic , clinical , and personality characteristics of patients ( N=256 ) with major depressive disorder ( MDD ) receiving antidepressant medication or interpersonal therapy as part of an RCT investigation ( n=105 ) versus in a clinic ( n=151 ) . The RCT and clinic protocol s were identical with the exception of recruitment procedures ( advertisement versus physician referral ) and assignment to treatment ( r and omized versus nonr and omized ) . Results : No significant differences emerged between the RCT participants and clinic patients for sex , age , marital status , and education . Overall , clinic patients were no more severely depressed compared to RCT participants ; there was , however , a significant interaction effect . Response rates were significantly higher for RCT participants versus clinic patients . Those participating in the RCT scored significantly higher on a personality scale assessing preference for novel experiences compared to those in the clinic . Conclusions : Differences in clinical and personality variables between those receiving treatment for MDD as part of an RCT versus in a clinic exist ; however , the clinical significance of these differences remains in question , as these variables were unrelated to treatment outcome . Depression and Anxiety , 2009 . © 2009 Wiley‐Liss , A new wave of meta-analyses suggests that antidepressants are no better than placebo for major depressive disorder ( MDD ) , and therefore , antidepressants not only do n't work , but even worse , they harm patients because of the risk of adverse effects . The authors analyzed data from all antidepressant studies su bmi tted to the Food and Drug Administration for registration ( including failed studies with inordinately high placebo reponses ) , or used a met analysis filter and selected those few studies that meet those criteria . In aggregate , the data , at best , show a clinical ly trivial advantage of the antidepressants over placebo in acute r and omized trials . However , their conclusions range from antidepressants do n't work at all to the antidepressants should be reserved only for the most seriously depressed patients . Kirsch is capitalizing on this trend with his recently published book . I view this debate through my perspective of over 25 years of clinical experience , serving as a rater for clinical trials , planning and conducting National Institute of Mental Health and industry efficacy and effectiveness clinical trials , and consulting to the pharmaceutical industry . The real story , I believe , is a bit more complicated . Give everyone with fever penicillin and many will improve . Compare penicillin to placebo and on average , you would find no difference . Why ? Most people with fever have viral infections or non-penicillin sensitive bacterial infections that are time limited ( eg , common upper respiratory infections ) . One could reasonably conclude that penicillin does n't work and we should all take chicken soup instead . Give everyone with MDD an antidepressant and many will improve . Compare any given antidepressant to placebo and on average , you should find no difference . Yet , a difference does exist and even if the trials have an overall small effect size in favor of antidepressants , it is not quite accurate to state that antidepressants are equal to placebo . Why ? If that were true , then in a third of the trials placebo would beat antidepressants , in a third of the trials antidepressants would beat placebo , and the remaining third of the trials it would be a tie . MDD is analogous to fever . It is a heterogeneous , nonspecific syndrome that is the final common pathway of multiple dysregulated psychological and brain processes . Genetic epidemiological studies strongly suggest that stress is a causal factor and that the persistence or The assumption that depressed patients who are assigned to placebo in antidepressant clinical trials are exposed to substantial morbidity and mortality has not been based on research data . Because of worldwide concern about placebo use and the implication s of our earlier findings of no increased suicide risk in placebo-treated patients , we conducted a replication study in a new patient sample . We assessed suicide risk and symptom reduction among placebo-treated patients participating in antidepressant clinical trials for two recently approved antidepressants , venlafaxine ER and citalopram , which were unavailable during our previous study . Among 23,201 participant patients , 32 committed suicide and 172 attempted suicide . Rates of suicide and attempted suicide did not differ significantly among the placebo- and drug-treated groups . Based on patient exposure years , annual rates of suicide and attempted suicide were 0.5 and 6.7 % with placebo , 0.9 % with active comparator ( rates for attempted suicide are unavailable ) , and 0.6 and 6.3 % with investigational antidepressants . Symptom reduction was 47.9 % with investigational drugs ( n = 1172 ) , 47.5 % with active comparators ( n = 161 ) , and 35.5 % with placebo ( n = 606 ) . These data may inform discussion s about the use of placebo in antidepressant clinical trials |
2,165 | 23,881,657 | Results of this review support the existing evidence that intermittent antipsychotic treatment is not as effective as continuous , maintained antipsychotic therapy in preventing relapse in people with schizophrenia . | BACKGROUND Antipsychotic medication is considered the mainstay of treatment for schizophrenia and is generally regarded as highly effective , especially in controlling positive symptoms .
However , long-term antipsychotic exposure has been associated with a range of adverse effects , including extra-pyramidal symptoms ( EPS ) , neuroleptic malignant syndrome ( NMS ) , tardive dyskinesia and death .
Intermittent drug techniques refers to the ' use of medication only during periods of incipient relapse or symptom exacerbation rather than continuously ' .
The aim is to reduce the risk of typical adverse effects of antipsychotics by ' reducing long-term medication exposure for patients who are receiving maintenance treatment while limiting the risk of relapse ' , with a further goal of improving social functioning result ing from the reduction of antipsychotic-induced side effects OBJECTIVES To review the effects of different intermittent drug techniques compared with maintenance treatment in people with schizophrenia or related disorders . | Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics , and to be more sensitive to developing extrapyramidal side-effects . The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol . Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms . Patients were r and omly assigned under double-blind conditions to receive risperidone ( n=143 ) or haloperidol ( n=146 ) for 8 wk . The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale ( PANSS ) negative score between treatment groups ; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores , and several other measures of psychopathology and general functioning . The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale ( SAS ) compared between treatment groups . The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms . Secondary tolerability criteria were the other extrapyramidal symptoms , measured with the Hillside Akathisia Scale ( HAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) . The average mean daily doses were 3.8 mg ( s.d.=1.5 ) for risperidone and 3.7 mg ( s.d.=1.5 ) for haloperidol . There were similar , significant improvements in both treatment groups in the primary and secondary efficacy criteria . At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [ SAS : risperidone 36.5 % of patients ; haloperidol 51.5 % of patients ; likelihood ratio test , chi2(1)=7.8 , p=0.005 ] . There were significantly fewer drop-outs [ risperidone n=55 , drop-out rate=38.5 % ; haloperidol n=79 , drop-out rate=54.1 % , chi2(1)=7.1 , p=0.009 ] and a longer non-discontinuation time [ risperidone : average of 50.8 d to drop-out ; haloperidol : average of 44.0 d to drop-out ; log rank test , chi2(1)=6.4 , p=0.011 ] in the risperidone group . Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia . Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients Abstract .In first-episode schizophrenia the advantage of new atypical neuroleptics compared to low-dose haloperidol as well as the indicated duration of neuroleptic maintenance treatment has still to be based on empirical evidence .Accordingly , a multi-center study on the optimization of acute and long-term treatment in first-episode schizophrenia is currently being carried out as part of the German Research Network on Schizophrenia . This paper reports on the design , methods and preliminary results of the two-year r and omized double-blind study comparing risperidone and low-dose haloperidol within the framework of psychological interventions . In the second treatment year , relapse rates under continued neuroleptic treatment are compared with those under stepwise drug withdrawal substituting instead prodrome-based early intervention ( intermittent treatment).As to the results , by November 2003 142 first episode patients ( ICD-10 F20 ) have been included in the long-term study . One-year relapse rates were very low ( 3.8 % ) . On average , symptoms as well as drug side-effects decreased steadily under maintenance treatment . Although compliance on average was high , about 60 % of the patients dropped out during the first study year . More pronounced psychopathology , ( neurological ) side-effects , lower compliance at study entry and absence of psychological treatment seemed to enhance the risk for drop-out . In conclusion , treatment in first episode schizophrenia is effective under both ( further on blinded ) neuroleptics ; however these patients are at high risk for treatment drop-out . This emphasizes the need for a special support program Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related . Methods To evaluate dose effect in response on primary efficacy scales from 2 r and omized , double-blind , flexible-dose trials of patients with bipolar mania who received olanzapine ( N = 234 , 5–20 mg/day ) , or patients with schizophrenia who received olanzapine ( N = 172 , 10–20 mg/day ) , we used marginal structural models , inverse probability of treatment weighting ( MSM , IPTW ) methodology . Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model . To adjust for selection bias due to non-r and om dose assignment and dropouts , patient-specific time-dependent weights were determined as products of ( i ) stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by ( ii ) stable weights based on inverse probability of patient remaining on treatment by that time . Results were compared with those by unweighted analyses . Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses , the weighted analyses showed no strong dose effects and , in some cases , reversed the apparent " negative dose effect . " Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses , the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect , which may prove useful for planning confirmatory trials OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate A double-blind , placebo-controlled trial was carried out to determine the value of maintenance therapy with phenothiazines in a population of out patients who had recently recovered from an acute episode of schizophrenia . The drug was shown to be significantly more effective than the placebo in preventing relapse . The relationship of the trial patients to the population from which they were selected was defined in terms of clinical , historical , and social data . Maintenance therapy seems of little value in patients with a good prognosis and in the severely ill , but it is of value in the indeterminate group between these two extremes A study was conducted to investigate a novel approach to the prophylaxis of schizophrenic relapse . The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared . Fifty four stable , remitted out patients meeting the American Psychiatric Association 's DSM-III criteria for schizophrenia were r and omised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections . Only three patients given placebo injections and two controls were admitted to hospital during one year of follow up . Eight ( 30 % ) of the patients given placebo injections and only 2 ( 7 % ) of the controls , however , had a recurrence of schizophrenic symptoms . Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia . Dysphoric and neurotic symptoms were identified before eight out of 11 relapses , and these symptoms were more frequent in patients given placebo depot injections . These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill , chronic , stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse The authors report on the outcome of treatment of 116 out patients with chronic schizophrenia who were assigned to a 2-year , single-blind course of treatment with either targeted or continuous medication . These patients were not restricted to those who were good c and i date s for a medication reduction strategy . Continuous medication was superior to targeted medication in preventing decompensations and hospitalizations and in extent of employment at 2 years . Other measures of psychopathology and functioning at 1 and 2 years did not differentiate the two groups of patients . The targeted approach achieved a substantial reduction in total medication through a reduction in the number of days of medication administration In a double-blind trial , 34 male chronic schizophrenic day- patients or in- patients in a hostel ward continued on fluphenazine decanoate given mostly once fortnightly or were switched to pimozide , given on four days each week . Over nine months relapse rates were similar for both groups , and while fewer patients on pimozide were prescribed antiparkinsonian drugs one quarter developed buccolingual masticatory dyskinesia . Plasma pimozide levels suggested satisfactory drug compliance . Average plasma prolactin levels were within the normal rage for untreated men in one quarter of non-relapsing patients on pimozide and three quarters on fluphenazine Summary Schizophrenic out patients ( = 364 ) were assigned at r and om to three different treatment strategies : ( 1 ) continuous medication with neuroleptic drugs , ( 2 ) intermittent medication with crisis intervention and ( 3 ) intermittent medication with early intervention . Depressive syndromes were rated according to three different scales for depressive syndromes ( Brief Psychiatric Rating Scale anxious depression factor , Arbeitsgemeinschaft für Method ik und Dokumentation in der Psychiatrie/depression , and the self-rating Paranoid Depression Scale ) after 1 and 2 years of treatment . No differences in depression scores were found between the three treatment strategies . Comparisons between patients treated with neuroleptic drugs at the time and patients without neuroleptics revealed significantly higher depression scores in the neuroleptics group in most comparisons . No differences were found between patients treated with low versus high potency neuroleptics and between oral versus depot neuroleptics . However , depression correlated with extrapyramidal symptoms The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Results of studies on intermittent neuroleptic treatment strategies in first episode ( FE ) schizophrenia have not been published . Aims of the present study were to eluci date the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode ( ME ) schizophrenia . As to the methods , three r and omly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic out patients ( 115 FE , 248 ME ; ICD-9 , RDC ) : maintenance medication vs two intermittent medication strategies ( prodrome-based intervention and crisis intervention ) . Concerning relapse prevention , the results demonstrate that ME patients seemed to profit most from maintenance medication compared to both intermittent treatments , whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment . Psychopathology , social adjustment , subjective well-being , and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy . Concerning treatment adherence , FE patients complied better with prodrome-based intervention than with maintenance medication . Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment . In conclusion , maintenance medication is the best strategy for relapse prevention in ME patients . In FE patients , prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied An open comparative trial was conducted involving 42 schizophrenic out patients r and omly assigned to one of two methods of drug administration : continuous medication ( N = 21 ) and targeted medication plus psychosocial intervention ( N = 21 ) . The results , which suggest an extensive similarity with respect to outcome for the two treatments over a 2-year period , argue for the continuation of research on the relative effectiveness of the targeted drug approach , particularly in cases judged suitable for drug reduction strategies BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism The World Health Organization has recently produced a generic quality of life measure – the WHOQOL-100 , together with an abbreviated version , the WHOQOL-BREF . Preliminary data suggest that the WHOQOL BREF provides a valid and reliable alternative to the lengthier WHOQOL-100 . In the present study , the sensitivity to change of both versions was tested pre- and 3 months post liver transplantation in fifty patients and also in twenty-one non-transplanted liver disease controls . Quality of Life domains on both measures were highly correlated , and were sensitive to change following transplant and remained stable on repeat assessment in non-transplanted control patients . However , the sensitivity to change was significantly reduced for the Social domain in the WHOQOL BREF . It is concluded that the WHO-QOL-BREF is a useful alternative to the WHOQOL-100 in evaluating quality of life improvement following major therapeutic interventions for Physical , Psychological and Environmental domains of life quality . However , research ers interested in measuring the Social aspects of life quality may be best advised to use the lengthier WHOQOL-100 OBJECTIVE Second-generation antipsychotics ( SGAs ) have proven superior to first-generation antipsychotics regarding relapse prevention , mainly in multiple-episode patients . Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients , although evidence for this group is still limited . Accordingly , the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested . METHOD Between November 2000 and May 2004 , 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals . 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria . In the r and omized controlled trial , double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year . 151 patients were eligible for analysis . For 127 patients , this was a continuation trial after 8 weeks of r and omized , double-blind , acute treatment with the same drugs ; 24 patients were additionally r and omly assigned after open acute treatment . RESULTS With both antipsychotics ( risperidone , N = 77 ; haloperidol , N = 74 ) , no relapse evolved . Additionally , according to 2 post hoc defined measures of " marked clinical deterioration , " significant differences occurred neither in the 2 respective deterioration rates ( risperidone = 9%/23 % ; haloperidol = 8%/22 % ) nor in time until deterioration . Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life . Extrapyramidal symptoms were slightly higher with haloperidol . The overall dropout rate of 68 % , however , was not significantly different between the 2 drug groups . CONCLUSION Against the background of an overall favorable outcome , the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia . Possible design -related reasons for this finding are discussed . With regard to the high dropout rate , special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier : NCT00159081 Abstract A sample of 85 patients with schizophrenia , of whom 34 later dropped out , received r and omised treatment . There were no significant differences between treatment-takers and drop-outs in the variables assessed . Patients received either st and ard-dose maintenance neuroleptic treatment or targeted maintenance pharmacotherapy and all patients received behavioural family therapy . Measures of psychopathology , social adjustment , side-effects , family burden , and expressed emotion were assessed at baseline and then periodically over an 18-month period . The study was design ed to compare the two alternative pharmacological maintenance approaches , each of them supported by psychosocial intervention . Any evaluation of the impact of behavioural family treatment on relapse rates and other outcome criteria is exclusively descriptive . A significantly higher rate of relapse was observed at 18 months in patients r and omised to targeted treatment compared to those r and omised to st and ard-dose treatment ( 35 % vs 4 % ) . Although patients assigned to the targeted maintenance group received significantly lower mean doses of neuroleptics , there were no significant differences between the two groups with regard to side-effects , global measures of social function , and overall psychopathology . Family burden was higher in the targeted-treatment group at six months , but did not differ at the one-year and eighteen-month time points . However , both groups improved significantly from baseline to 12 or 18 months in almost all variables assessed . Thus , the behavioural family approach did not compensate for the problems associated with the targeted medication strategy Abstract Objective To compare two widely used drug treatments for people with aggression or agitation due to mental illness . Design Pragmatic , r and omised clinical trial . Setting Three psychiatric emergency rooms in Rio de Janeiro , Brazil . Subjects 301 aggressive or agitated people . Interventions Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine . Main outcome measures Patients tranquil or se date d at 20 minutes . Secondary outcomes : patients tranquil or asleep by 40 , 60 , and 120 minutes ; restrained or given extra drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; needing extra visits from doctor during first 24 hours ; overall antipsychotic load in first 24 hours ; and not discharged by two weeks . Results 151 patients were r and omised to midazolam , and 150 to haloperidol-promethazine mix . Follow up for the primary outcome was available for 298 ( 99 % ) : 134/151 ( 89 % ) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 ( 67 % ) of those given haloperidol plus promethazine ( relative risk 1.32 ( 95 % confidence interval 1.16 to 1.49 ) ) . By 40 minutes , midazolam still had a statistically and clinical ly significant 13 % relative advantage ( 1.13 ( 1.01 to 1.26 ) ) . After 1 hour , about 90 % of both groups were tranquil or asleep . One important adverse event occurred in each group : a patient given midazolam had transient respiratory depression , and one given haloperidol-promethazine had a gr and e mal seizure . Conclusions Both treatments were effective . Midazolam was more rapidly sedating than haloperidol-promethazine , reducing the time people are exposed to aggression . Adverse effects and re sources to deal with them should be considered in the choice of the treatment BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam BACKGROUND Previous studies have examined dose reduction and family treatment in schizophrenia , but none has examined their interaction . This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment . METHODS Subjects were 313 male and female out patients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder . In a 3 x 2 design , subjects were r and omized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions : continuous moderate dose ( st and ard ) ( 12.5 - 50 mg every 2 weeks ) ; continuous low dose ( 2.5 - 10 mg every 2 weeks ) ; or targeted , early intervention ( fluphenazine only when symptomatic ) . Subjects also were r and omized to 1 of 2 family treatment strategies ( supportive or applied ) . Supportive family management involved monthly group meetings . The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught . Patients and families were treated and assessed for 2 years . RESULTS Both continuous low-dose and targeted treatment increased use of rescue medication and relapse ; only targeted treatment increased rehospitalization . This pattern was consistent across both family treatments ; there were no differences between family treatments . CONCLUSIONS These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization . The absence of family treatment differences may be because both conditions engaged families The author review s six topics relevant to the drug treatment of schizophrenia . The quantitative effectiveness of promazine is of interest with respect to the structural models of the phenothiazines and the dopamine theory of schizophrenia . The quantitative effectiveness of antipsychotic drugs is also important in evaluating new agents and therefore relevant to a discussion of two newly released neuroleptics , molindone and loxapine . The author 's discussion of high-dose treatment of typical acute schizophrenics or treatment-resistant patients review s the available data and calls attention to the fact that these areas of pharmacologic research have not received sufficient attention All recently completed controlled two-year studies on intermittent , early neuroleptic intervention treatment have failed to compare favourably with studies on maintenance treatment concerning relapse prevention . The reason for this failure is still unclear . Therefore the implicit , but as yet unproven , hypothesis that a relapse can be predicted from prodromal symptoms was tested from the perspective of our German multicentre study . Results demonstrate that this is not the case . Possible reasons for and clinical implication s of this negative finding are discussed This is a 2-year , double-blind , placebo-controlled study of 101 patients , evaluating the relative efficacy of intermittent medication ( given only when the patient shows early signs of relapse ) compared with moderate doses of maintenance medication for stable schizophrenic out patients . Patients were dropped from the study if they had three prodromal episodes in 1 year or if an episode lasted more than 9 weeks . Fourteen percent of patients given maintenance treatment were dropped from the study compared with 46 % of intermittently treated patients . Relapse rates were 16 % for patients given maintenance treatment and 30 % for intermittently treated patients , a nonsignificant difference . Intermittently treated patients were receiving significantly less medication , but there were no differences found in drug side effects . There appears to be no advantage in using the intermittent approach , but we found that the use of an early intervention strategy reduced the relapse and rehospitalization rates for these patients A follow-up study of all patients entering the MRC double-blind trial of fluphenazine decanoate in chronic schizophrenic out- patients achieved a trace rate of 94 % . In general , these patients were severely disabled , continued under the care of the maintenance clinic , and their diagnoses remained remarkably consistent ; more than one-fifth were found to be in acute schizophrenic relapse and in over a half of these cases , the relapse was not known to the treatment agency . The maintenance clinic attenders were little different from those who no longer used such a facility OBJECTIVE After acute treatment of the first illness episode in schizophrenia , antipsychotic maintenance treatment is recommended for at least 1 year . Evidence for the optimal subsequent treatment is still scarce . Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients ; however , a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients . The current study was therefore design ed to compare prospect ively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia . METHOD A r and omized controlled trial was conducted within the German Research Network on Schizophrenia . Entry screening took place between November 2000 and May 2004 . After 1 year of antipsychotic maintenance treatment , stable first-episode patients were r and omly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment . In case of prodromal symptoms of an impending relapse , patients in both groups received early drug intervention , guided by a decision algorithm . The primary outcome measure was relapse ( increase in the Positive and Negative Syndrome Scale positive score > 10 , Clinical Global Impressions-Change score ≥ 6 , and decrease in Global Assessment of Functioning score > 20 between 2 visits ) . RESULTS Of 96 first-episode patients , only 44 were eligible for the assigned treatment ( maintenance treatment , n = 23 ; intermittent treatment , n = 21 ) . The rates of relapse ( 19 % vs 0 % ; P = .04 ) and deterioration ( up to 57 % vs 4 % ; P < .001 ) were significantly higher in the intermittent treatment group than in the maintenance treatment group , but quality -of-life scores were comparable . Intermittent treatment patients received a significantly lower amount of antipsychotics ( in haloperidol equivalents ; P < .001 ) and tended to show fewer side effects , particularly extrapyramidal side effects . CONCLUSIONS Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse , even in stable first-episode patients after 1 year of maintenance treatment , and should be the preferred treatment option . However , about 50 % of patients remain stable at a significantly lower drug dose and show fewer side effects , and a substantial proportion refuse maintenance treatment . Alternative long-term treatment strategies , including targeted intermittent treatment , should therefore be provided in individual cases . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00159120 We have conducted a 6-wk drug withdrawal study in a group of chronic schizophrenic out patients who had been maintained on injectable fluphenazine decanoate for at least 2 yr prior to the study . After two baseline assessment s , patients were r and omly assigned to two groups . The first group ( holiday ) received a placebo injection from a nurse who was not involved in the assessment ( N = 17 ) . The second group continued on their regular medication ( N = 14 ) . The assessment was done in a double-blind fashion at 3 and 6 wk using the Schedule for Affective Disorders and Schizophrenia ( SADS ) and the Global Assessment Scale ( GAS ) inventories to assess symptom status . Tardive dyskinesia was measured using the Abnormal Involuntary Movement Scale ( AIMS ) . Community adjustment was assessed by means of the self-rated Weissman Social Adjustment Scale . We found that there were no relapses of any kind in either group of patients using the instruments mentioned above . The prevalence of tardive dyskinesia as measured by the AIMS was low , with only one patient having severe tardive dyskinesia . There was no significant worsening of the tardive dyskinesia during the drug holiday . Our study concludes that a 6-wk drug holiday was safe in this group of chronic schizophrenic patients maintained on fluphenazine decanoate . In contrast to other studies , no cases of covert tardive dyskinesia were detected during the drug holiday OBJECTIVE In the treatment of schizophrenia , all currently available oral antipsychotics are administered at least once daily , with strict adherence strongly encouraged to minimize risk of relapse . Based on a better underst and ing of the brain kinetics of antipsychotics , we have proposed a variation of this approach , " extended " dosing , which allows for intermittent but regular dosing . METHOD We carried out a r and omized , double-blind , placebo-controlled trial evaluating 35 individuals with DSM-IV-defined schizophrenia who had been stabilized on antipsychotic therapy . Over a 6-month interval , 18 subjects received their medication as usual ( daily ) , while 17 received their antipsychotic therapy every second day ( extended ) . Outcome measures included clinical scales to assess symptoms ( Brief Psychiatric Rating Scale [ the primary outcome measure ] , Calgary Depression Scale ) , illness severity ( Clinical Global Impressions-Severity of Illness scale ) , and relapse ( ie , rehospitalization ) rates . Side effects were also assessed , including movement disorders ( Barnes Akathisia Scale , Simpson-Angus Scale , Abnormal Involuntary Movement Scale ) and weight . The study was conducted from February 2003 to July 2007 . RESULTS Individuals in the extended dosing group were not at greater risk of symptom exacerbation , relapse , or rehospitalization ; indeed , more rehospitalizations occurred in those receiving regular dosing . At the same time , though , there was no indication that side effects were significantly reduced in the extended dosing group . CONCLUSIONS These results challenge the long-st and ing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia . Further studies with larger sample s are needed to replicate these findings , as well as to eluci date whether postulated clinical advantages can be established and determined to outweigh potential risks . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00431574 A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials In neuroleptic long-term medication , only part of the patients accept regular intake of neuroleptic drugs . The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication . In a 2-year prospect i ve study , 122 patients were r and omised to an interval and 164 to a continuous neuroleptic medication regimen . The drop out rates were 62.5 % in the interval and 53.7 % in the continuous medication group . Drop outs generally show more negative attitudes towards treatment . Patients with negative attitudes do not do better under interval medication . Moreover , this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen . Interval medication therefore is a strategy which can only be successful in highly cooperative , but not in treatment-reluctant patients In an 18-hospital collaborative study , 375 chronic schizophrenics on stable maintenance doses of anti-psychotic drugs were assigned to one of four groups in which medication was withdrawn two or three days a week on varying schedules , or to one in which daily medication was continued . At the end of 16 weeks , there was no significant difference in relapse rate between the continued-treatment and intermittent-treatment groups . That finding suggests that short-term intermittent drug withdrawal is a feasible treatment policy for hospitalized chronic schizophrenics on maintenance chemotherapy . The benefits of a successful intermittent therapy program include less risk of toxicity for the patient ; less work for the staff , allowing more time for other therapeutic activities ; and lower drug costs for the hospital Planning a major , multicentre study on effects of neuroleptic treatment in schizophrenic out patients requires attention to many method ological , ethical and administrative matters . This report describes the study planned by the German neuroleptic therapy study group . Three types of treatment have been chosen : prophylactic maintenance medication , neuroleptic crisis intervention and prophylactic early intervention . Patients who meet the criteria for inclusion in the study are assigned to each treatment on a r and om basis , provided their informed consent has been obtained . Their psychopathological symptoms , social status and physical condition are measured by means of st and ardised examinations and rating scales . The study is expected to continue during five years , after which computerised data analysis will be carried out to test the central hypotheses for the study |
2,166 | 21,104,469 | Psychological interventions changed neural circuits involved in the pathophysiology of anxiety disorders , especially activity in frontal-striatal circuits in OCD and prefrontal areas in arachnophobia .
Despite the variety of method ological concerns , initial neuroimaging studies have showed that psychological interventions can change brain function related to anxiety disorders in the patients who respond to treatment . | INTRODUCTION Psychological therapies can modify thoughts , feelings , and behaviors of people with mental disorders , but the underlying brain mechanisms remain to be clarified .
Advances in neuroimaging techniques can help us to underst and of how different psychotherapies change the human brain .
This review has aim ed to systematic ally investigate the brain effects of psychological therapies for adults with anxiety disorders . | Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders . The present study aim ed to identify changes in brain activation following cognitive-behavioral therapy ( CBT ) in subjects suffering from specific phobia . Using functional magnetic resonance imaging ( fMRI ) , brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects . Phobics were r and omly assigned to a therapy-group ( TG ) and a waiting-list control group ( WG ) . Both groups of phobics were scanned twice . Between scanning sessions , CBT was given to the TG . Before therapy , brain activation did not differ between both groups of phobics . As compared to control subjects , phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex ( ACC ) . CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged . In the second scanning session , a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG . These results propose that increased activation in the insula and ACC is associated with specific phobia , whereas an attenuation of these brain responses correlates with successful therapeutic intervention Neurofunctional mechanisms underlying cognitive behavior therapy ( CBT ) are still not clearly understood . This functional magnetic resonance imaging ( fMRI ) study focused on changes in brain activation as a result of one-session CBT in patients suffering from spider phobia . Twenty-six female spider phobics and 25 non-phobic subjects were presented with spider pictures , generally disgust-inducing , generally fear-inducing and affectively neutral scenes in an initial fMRI session . Afterwards , the patients were r and omly assigned to either a therapy group ( TG ) or a waiting list group ( WG ) . The scans were repeated one week after the treatment or after a one-week waiting period . Relative to the non-phobic participants , the patients displayed increased activation in the amygdala and the fusiform gyrus as well as decreased activation in the medial orbitofrontal cortex ( OFC ) during the first exposure . The therapy effect consisted of increased medial OFC activity in the TG relative to the WG . Further , therapy-related reductions in experienced somatic anxiety symptoms were positively correlated with activation decreases in the amygdala and the insula . We conclude that successful treatment of spider phobia is primarily accompanied by functional changes of the medial OFC . This brain region is crucial for the self-regulation of emotions and the relearning of stimulus-reinforcement associations BACKGROUND Neurofunctional changes underlying effective antianxiety treatments are incompletely characterized . This study explored the effects of citalopram and cognitive-behavioral therapy on regional cerebral blood flow ( rCBF ) in social phobia . METHODS By means of positron emission tomography with oxygen 15-labeled water , rCBF was assessed in 18 previously untreated patients with social phobia during an anxiogenic public speaking task . Patients were matched for sex , age , and phobia severity , based on social anxiety question naire data , and r and omized to citalopram medication , cognitive-behavioral group therapy , or a waiting-list control group . Scans were repeated after 9 weeks of treatment or waiting time . Outcome was assessed by subjective and psychophysiological state anxiety measures and self-report question naires . Questions were readministered after 1 year . RESULTS Symptoms improved significantly and roughly equally with citalopram and cognitive-behavioral therapy , whereas the waiting-list group remained unchanged . Four patients in each treated group and 1 waiting-list patient were classified as responders . Within both treated groups , and in responders regardless of treatment approach , improvement was accompanied by a decreased rCBF-response to public speaking bilaterally in the amygdala , hippocampus , and the periamygdaloid , rhinal , and parahippocampal cortices . Between-group comparisons confirmed that rCBF in these regions decreased significantly more in treated groups than control subjects , and in responders than nonresponders , particularly in the right hemisphere . The degree of amygdalar-limbic attenuation was associated with clinical improvement a year later . CONCLUSIONS Common sites of action for citalopram and cognitive-behavioral treatment of social anxiety were observed in the amygdala , hippocampus , and neighboring cortical areas , ie , brain regions subserving bodily defense reactions to threat BACKGROUND Functional brain imaging studies in major depression have suggested abnormalities of areas , including the frontal cortex , cingulate gyrus , basal ganglia , and temporal cortex . We hypothesized that venlafaxine hydrochloride and interpersonal psychotherapy ( IPT ) might each alter brain blood flow in some or all of these areas on sequential single photon emission computed tomography ( SPECT ) scans . METHODS Twenty-eight men and women aged 30 to 53 years with a DSM-IV major depressive episode , a 17-item Hamilton Rating Scale for Depression ( HAM-D ) rating of 18 or higher , and antidepressant-naive for at least 6 months were studied . After baseline (99m)technetium-hexa-methyl-propylene-amine-oxime scan , 1-T magnetic resonance imaging , and psychometric ratings , patients were assigned to different treatments . Thirteen patients had 1-hour weekly sessions of IPT from the same supervised therapist ( E.M. ) . Fifteen patients took 37.5 mg twice-daily of venlafaxine hydrochloride . Single-photon emission computed tomography scans and ratings were repeated at 6 weeks . RESULTS Both treatment groups improved substantially , more so with venlafaxine ( mean [ SD ] HAM-D scores at pretreatment : IPT , 22.7 [ 2.7 ] , and venlafaxine , 22.4 [ 3.1 ] ; and posttreatment : IPT , 16.2 [ 7.1 ] , and venlafaxine , 10.9 [ 8.6 ] ) . No patients had structural brain abnormalities . On analysis with statistical parametric mapping 96 , the venlafaxine group showed right posterior temporal and right basal ganglia activation ( P = .01 ) , while the IPT group had limbic right posterior cingulate and right basal ganglia activation ( P = .01 ) . CONCLUSIONS This preliminary investigation has shown limbic blood flow increase with IPT yet not venlafaxine , while both treatments demonstrated increased basal ganglia blood flow . This was , however , a short trial with a small sample , no control group , and different symptom reduction in the 2 groups BACKGROUND Magnetic resonance imaging ( MRI ) studies have especially reported smaller hippocampal volume in patients with post-traumatic stress disorder ( PTSD ) , most of them war or sexual abuse victims . The present study compares the hippocampal volumes of out- patients with PTSD who had low co-morbidity rates to those of trauma-exposed control subjects without PTSD , and measures hippocampal volume changes in these patients after brief eclectic psychotherapy . We hypothesized that smaller hippocampal volumes are specific to PTSD and that hippocampal volume changes after effective psychotherapy would be measurable . METHOD Eighteen patients with PTSD and 14 traumatized control subjects were examined with MRI . In a r and omized clinical trial , the PTSD patients were assigned to treatment ( n = 9 ) or waiting-list group ( n = 9 ) . After the former received psychotherapy for 4 months , the MRI was repeated on both PTSD groups . Three temporal lobe structures were manually segmented : hippocampus , amygdala , and parahippocampal gyrus . Volumetric analysis was used to measure grey matter , white matter , and cerebrospinal fluid . RESULTS PTSD patients had significantly smaller hippocampal volumes at baseline ( total 13.8 % , right 13.5 % , left 14.1 % ) compared to the control subjects . After effective psychotherapy , however , no volume changes were found in the smaller hippocampi . CONCLUSIONS We confirmed previous findings of smaller hippocampal volume in PTSD in a new population made up of out- patients who experienced different types of traumas , reducing co-morbidity to a minimum . Smaller hippocampal volumes did not change after effective psychotherapy , even while symptoms resolved Background Post-traumatic stress disorder ( PTSD ) is a derangement of mood control with involuntary , emotionally fraught re collection s that may follow deep psychological trauma in susceptible individuals . This condition is treated with pharmacological and /or cognitive therapies as well as psychotherapy with eye movement desensitization and reprocessing ( EMDR ) . However , only a very limited number of studies have been published dealing with work-related PTSD , and investigations on the effect of treatment on cerebral blood flow represent an even smaller number . Aim To investigate the short-term outcome of occupation-related PTSD after EMDR therapy by 99mTc-HMPAO SPECT . Method Fifteen patients , either train drivers suffering from PTSD after having been unintentionally responsible for a person-under-train accident or employees assaulted in the course of duty , were recruited for the study . 99mTc-HMPAO SPECT was performed on these patients both before and after EMDR therapy while they listened to a script portraying the traumatic event . Tracer distribution analysis was then carried out at volume of interest ( VOI ) level using a three-dimensional st and ardized brain atlas , and at voxel level by SPM . The CBF data of the 15 patients were compared before and after treatment as well as with those of a group of 27 controls who had been exposed to the same psychological traumas without developing PTSD . Results At VOI analysis significant CBF distribution differences were found between controls and patients before and after treatment ( P=0.023 and P=0.0039 , respectively ) . Eleven of the 15 patients responded to treatment , i.e. , following EMDR they no longer fulfilled the DSM-IV criteria for PTSD . When comparing only the eleven responders with the controls , the significant group difference found before EMDR ( P=0.019 ) disappeared after treatment . Responders and non-responders showed after therapy significant regional differences in frontal , parieto-occipital and visual cortex and in hippocampus . SPM analysis showed significant uptake differences between patients and controls in the orbitofrontal cortex ( Brodmann 11 ) and the temporal pole ( Brodmann 38 ) both before and after treatment . A significant tracer distribution difference present before treatment in the uncus ( Brodmann 36 ) disappeared after treatment , while a significant difference appeared in the lateral temporal lobe ( Brodmann 21 ) . ConclusionS ignificant 99mTc-HMPAO uptake regional differences were found , mainly in the peri-limbic cortex , between PTSD patients and controls exposed to trauma but not developing PTSD . Tracer uptake differences between responders and patients not responding to EMDR were found after treatment suggesting a trend towards normalization of tracer distribution after successful therapy . These findings in occupational related PTSD are consistent with previously described effects of psychotherapy on anxiety disorders Several neuroanatomical hypotheses of panic disorder have been proposed focusing on the significant role of the amygdala and PAG-related " panic neurocircuitry . " Although cognitive-behavioral therapy is effective in patients with panic disorder , its therapeutic mechanism of action in the brain remains unclear . The present study was performed to investigate regional brain glucose metabolic changes associated with successful completion of cognitive-behavioral therapy in panic disorder patients . The regional glucose utilization in patients with panic disorder was compared before and after cognitive-behavioral therapy using positron emission tomography with (18)F-fluorodeoxyglucose . In 11 of 12 patients who showed improvement after cognitive-behavioral therapy , decreased glucose utilization was detected in the right hippocampus , left anterior cingulate , left cerebellum , and pons , whereas increased glucose utilization was seen in the bilateral medial prefrontal cortices . Significant correlations were found between the percent change relative to the pretreatment value of glucose utilization in the left medial prefrontal cortex and those of anxiety and agoraphobia-related subscale of the Panic Disorder Severity Scale , and between that of the midbrain and that of the number of panic attacks during the 4 weeks before each scan in all 12 patients . The completion of successful cognitive-behavioral therapy involved not only reduction of the baseline hyperactivity in several brain areas but also adaptive metabolic changes of the bilateral medial prefrontal cortices in panic disorder patients BACKGROUND Functional brain-imaging studies in post-traumatic stress disorder ( PTSD ) have suggested functional alterations in temporal and prefrontal cortical regions . Effects of psychotherapy on these brain regions have not yet been examined . METHOD Twenty civilian PTSD out- patients and 15 traumatized control subjects were assessed at baseline using psychometric ratings . Cerebral blood flow was measured using trauma script-driven imagery during 99mtechnetium hexamethyl-propylene-amine-oxime single-photon emission computed tomography scanning . All 20 out- patients were r and omly assigned to treatment or wait-list conditions . Treatment was brief eclectic psychotherapy ( BEP ) in 16 weekly individual sessions . RESULTS At baseline , greater activation was found in the right insula and right superior/middle frontal gyrus in the PTSD group than in the control group . PTSD patients treated with BEP significantly improved on all PTSD symptom clusters compared to those on the waiting list . After effective psychotherapy , lower activation was measured in the right middle frontal gyrus , compared to the PTSD patients on the waiting list . Treatment effects on PTSD symptoms correlated positively with activation in the left superior temporal gyrus , and superior/middle frontal gyrus . CONCLUSIONS BEP induced clinical recovery in PTSD patients , and appeared to modulate the functioning of specific PTSD-related sites in the prefrontal cortical regions BACKGROUND The results of one r and omised control trial testing a psychological rehabilitation programme aim ed at information processing strategies showed improvements in cognition post-treatment . AIMS To determine whether there are concomitant brain activation changes as a result of engaging in cognitive remediation therapy ( CRT ) . METHOD Three groups ( patients receiving control therapy or CRT and a healthy control group ) were investigated in a repeated measures design using the two-back test . Functional magnetic resonance imaging ( fMRI ) data and a broad assessment of executive functioning were completed at baseline and post-treatment . Brain activation changes were identified after accounting for possible task-correlated motion artefact . RESULTS fMRI analyses indicate that the control group showed decreased activation but the two patient groups showed an increase in activation over time . The patient group that received successful CRT had significantly increased brain activation in regions associated with working memory , particularly the frontocortical areas . CONCLUSIONS This is the first time that brain activation changes in a seriously disabled group of patients with schizophrenia can be associated clearly with psychological rather than pharmacological therapy Objective : The effects of neuropsychological treatment on cognitive hypofrontality were examined in schizophrenic patients through the score activation BACKGROUND Cognitive behavioral therapy ( CBT ) with exposure and response prevention ( ERP ) is the psychotherapeutic treatment of choice for obsessive-compulsive disorder ( OCD ) . However , little is known about the impact of CBT on frontostriatal dysfunctioning , known to be the neuronal correlate of OCD . METHOD A probabilistic reversal learning ( RL ) task probing adaptive strategy switching capabilities was used in 10 unmedicated patients with OCD and 10 healthy controls during an event-related functional magnetic resonance imaging ( fMRI ) experiment . Patients were scanned before and after intensive CBT , controls twice at comparable intervals . RESULTS Strategy change within the RL task involved activity in a broad frontal network in patients and controls . No significant differences between the groups or in group by time interactions were detected in a whole-brain analysis corrected for multiple comparisons . However , a re analysis with a more lenient threshold revealed decreased responsiveness of the orbitofrontal cortex and right putamen during strategy change before treatment in patients compared with healthy subjects . A group by time effect was found in the cau date nucleus , demonstrating increased activity for patients over the course of time . Patients with greater clinical improvement , reflected by greater reductions in Yale-Brown Obsessive Compulsive Scale ( YBOCS ) scores , showed more stable activation in the pallidum . CONCLUSIONS Although these findings are preliminary and need to be replicated in larger sample s , they indicate a possible influence of psychotherapy on brain activity in core regions that have been shown to be directly involved both in acquisition of behavioral rules and stereotypes and in the pathophysiology of OCD , the cau date nucleus and the pallidum BACKGROUND Functional neuroimaging studies have implicated hyperactivity of the frontal cortex in obsessive-compulsive disorder ( OCD ) ; however , relationships between abnormal brain activity , clinical improvement , and neuropsychological function have not been clarified in OCD . To clarify the pathophysiology of this disorder , regional changes in brain function were examined during administration of cognitive and symptom provocation tasks in patients with OCD before and after treatment . METHODS Ten out patients with OCD participated in the study . Functional magnetic resonance imaging ( fMRI ) was performed before and after treatment . Stroop and symptom provocation tasks were administered during fMRI . Each patient was r and omly allocated to receive either pharmacotherapy with fluvoxamine 200 mg/day ( n = 4 ) or behavior therapy ( n = 6 ) for 12 weeks . RESULTS After 12-week treatment , mean ( + /- SD ) total score on the Yale-Brown Obsessive-Compulsive Scale decreased from 29.00 + /- 3.59 to 14.60 + /- 9.22 , representing symptomatic improvement from moderate to mild . After symptom improvement , symptom provocation-related activation in the orbitofrontal , dorsolateral-prefrontal , and anterior cingulate cortices decreased . Conversely , Stroop task-related activation in the parietal cortex and cerebellum increased . CONCLUSIONS After improvement of OCD with either fluvoxamine or behavioral therapy , hyperactivation of the frontal lobe related to a symptom-provocative state decreases , and posterior brain activity related to action-monitoring function increases |
2,167 | 23,675,431 | Although significant generalisation of learning was shown to untrained measures of speech intelligibility ( 11/13 articles ) , cognition ( 1/1 articles ) and self-reported hearing abilities ( 1/2 articles ) , improvements were small and not robust .
Where reported , compliance with computer-based auditory training was high , and retention of learning was shown at post-training follow-ups .
Our findings demonstrate that published evidence for the efficacy of individual computer-based auditory training for adults with hearing loss is not robust and therefore can not be reliably used to guide intervention at this time . | BACKGROUND Auditory training involves active listening to auditory stimuli and aims to improve performance in auditory tasks .
As such , auditory training is a potential intervention for the management of people with hearing loss .
OBJECTIVE This systematic review ( PROSPERO 2011 : CRD42011001406 ) evaluated the published evidence -base for the efficacy of individual computer-based auditory training to improve speech intelligibility , cognition and communication abilities in adults with hearing loss , with or without hearing aids or cochlear implants . | OBJECTIVES To show that hearing loss has such a high prevalence in the older population to justify screening , if effective and acceptable methods are available ; and that population take-up and benefit can make a measurable outcome difference in quality of life . DESIGN A population study of people aged 55 - 74 years was undertaken . A clinical effectiveness study of differently organised screening programmes was carried out using a controlled trial to identify those who might benefit from intervention ( and the extent of the benefit ) . A retrospective case-control study examined the very long-term ( more than 10 years ) compliance of patients in using their hearing aids after early identification and determined the extent to which early-identified hearing-impaired people have better outcomes than equivalent people identified later . An examination of the costs and cost-effectiveness of different potential screening programmes was also undertaken . SETTING A population study was design ed in the UK , with specific stages being conducted in more depth on a sample of people from Nottingham and Southampton . The clinical effectiveness study was conducted in general practice s in Nottingham and Bath using a systematic or opportunistic screen . The retrospective case-control study compared a group of early-identified hearing aid users , with control matched for age , gender and occupation , in Cardiff , Glasgow and Manchester . PARTICIPANTS In Great Britain responses were obtained for 34,362 individuals from the postal question naire as part of a population study , 506 were interviewed , 351 were assessed for benefit from amplification and 87 were fitted with a hearing aid . The clinical effectiveness study received 1461 replies from the first-stage question naire screen , with 306 people assessed in the clinic , of whom 156 were fitted with hearing aids . The retrospective case-control study traced 116 previously fitted hearing aid users , who had been identified by a screen , and then conducted a case-control using 50 of these for whom complete data were available , matching with two control groups of 50 people . INTERVENTIONS The major prospect i ve interventions were to introduce amplification through offering people , with minimal hearing impairment , hearing aid(s ) in a rehabilitative setting . In the population study , aids were offered as a monaural in-the-ear ( ITE ) hearing aid and in the clinical effectiveness study people who met the criteria were r and omised to be offered two different ITE hearing aids to be fitted bilaterally . The retrospective case-control study used unilateral and bilateral hearing aids . MAIN OUTCOME MEASURES Prevalence of hearing problems and degree to which services meet need in 55 - 74-year age group . Public acceptability and individual benefits of hearing screening and intervention as a function of demographic and hearing domain-specific characteristics . Improvement in quality of life . Screening costs and cost-effectiveness as a function of proposed programmes . RESULTS It was found that 12 % of people aged 55 - 74 years have a hearing problem that causes moderate or severe worry , annoyance or upset , 14 % have a bilateral hearing impairment of at least 35 dB hearing level ( HL ) and only 3 % currently receive intervention , through the use of hearing aids . Good amplification was shown to benefit about one in four of this 55 - 74-year-old population and the degree of hearing loss predicted benefit well . Overall , there was a strong correlation between benefit from amplification and from using hearing aids . Question naires and audiometric screens gave good screening operating characteristics . The systematic screening programme was more acceptable and gave a better response than the opportunistic . About 70 % of those who were offered an aid accepted a bilateral fitting . This increased to 95 % for those with > or = 35 dB HL ( averaged over 0.5 , 1 , 2 and 4 kHz in the better ear ) . The retrospective case-control study showed that long-term hearing aid use was low , unless hearing impairment was quite high ( e.g. > 35 dB HL ) . Those identified early had greater benefit through additional years of use/better adaptation to use than those of the same age and hearing impairment who were fitted with hearing aids later . Different screening programmes were modelled . The 35 dB HL better ear average hearing impairment level was found to be a good , robust and justifiable target group for screening and here the most efficient and practicable method was to use two questions in primary care concerning hearing problems and a hearing screen using a pure tone at 3 kHz 35 dB HL . The average cost of the screening programme was 13 pounds per person screened or about 100 pounds if treatment costs were included . Making the conservative assumption that identification gives an extra 9 years using hearing aids , the costs of screening and intervention were in the range of 800 - 1000 pounds per quality -adjusted life-year when using the Health Utilities Index and about 2500 pounds using the Short Form 6 Dimensions metric . CONCLUSIONS A simple systematic screen , using an audiometric screening instrument , has been shown to be acceptable to people in the age range 55 - 74 years , is likely to provide substantial benefit and may be cost-effective to those in that target group . Hearing screening appears to meet the National Screening Committee 's criteria in most respects , provided screening is targeted at those with at least 35 dB HL better ear average . Based on the research carried out here there is sufficient evidence to support a larger and more definitive study of hearing screening . Further research into who should be referred for and benefit from audiological assessment and provision of hearing aid in a primary care trust setting is needed as is investigation into screening devices and the various aspects of introducing such a programme Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Auditory training has long been advocated to enhance communication but has never been time or cost-effective . This article describes the concepts underlying the development of a home-based , interactive adaptive computer program design ed to engage the adult hearing-impaired listener in the hearing-aid-fitting process , provide listening strategies , build confidence , and address cognitive changes characteristic of the aging process . An investigation using a between-group , within-subject design with pre- and post-test objective and subjective measures was conducted at five clinical sites . Sixty-five subjects were r and omly placed into two groups , one receiving LACE ( Listening and Communication Enhancement ) immediately following baseline testing and one serving as a control for one month and then receiving training as a crossover group . Results showed statistically significant improvements for the trained subjects on all but one of the outcome measures . Barriers facing the widespread implementation of home-based aural rehabilitation are discussed Background Although feedback on performance is generally thought to promote perceptual learning , the role and necessity of feedback remain unclear . We investigated the effect of providing varying amounts of positive feedback while listeners attempted to discriminate between three identical tones on learning frequency discrimination . Methodology /Principal Findings Using this novel procedure , the feedback was meaningless and r and om in relation to the listeners ' responses , but the amount of feedback provided ( or lack thereof ) affected learning . We found that a group of listeners who received positive feedback on 10 % of the trials improved their performance on the task ( learned ) , while other groups provided either with excess ( 90 % ) or with no feedback did not learn . Superimposed on these group data , however , individual listeners showed other systematic changes of performance . In particular , those with lower non-verbal IQ who trained in the no feedback condition performed more poorly after training . Conclusions / Significance This pattern of results can not be accounted for by learning models that ascribe an external teacher role to feedback . We suggest , instead , that feedback is used to monitor performance on the task in relation to its perceived difficulty , and that listeners who learn without the benefit of feedback are adept at self-monitoring of performance , a trait that also supports better performance on non-verbal IQ tests . These results show that ‘ perceptual ’ learning is strongly influenced by top-down processes of motivation and intelligence A software system , SPATS ( patent pending ) , that tests and trains important bottom-up and combined bottom-up/top-down speech-perception skills is described . Bottom-up skills are the abilities to identify the constituents of syllables : onsets , nuclei , and codas in quiet and noise as produced by eight talkers . Top-down skills are the abilities to use knowledge of linguistic context to identify words in spoken sentences . The sentence module in SPATS emphasizes combined bottom-up/top-down abilities in perceiving sentences in noise . The word-initial onsets , stressed nuclei , and word-final codas are ranked in importance and grouped into subsets based on their importance . Testing utilizes r and om presentation of all the items included in a subset . Training in Quiet ( SNR = 40 dB ) or in Noise ( SNR = 5 dB ) , is adaptively focused on individual listener 's learnable items of intermediate difficulty . Alternatively , SNR-adaption training uses Kaernbach 's algorithm to find the SNR required for a target percent correct . The unique sentence module trains the combination of bottom-up ( hearing ) with top-down ( use of linguistic context ) abilities to identify words in meaningful sentences in noise . Scoring in the sentence module is objective and automatic We assessed the effects of perceptual training of syllable identification in noise on nonsense syllable test ( NST ) performance of new ( Experiment 1 ) and experienced ( Experiment 2 ) hearing aid ( HA ) users with sensorineural hearing loss . In Experiment 1 , new HA users were r and omly assigned to either immediate training ( IT ) or delayed training ( DT ) groups . IT subjects underwent 8 weeks of at-home syllable identification training and in-laboratory testing , whereas DT subjects underwent identical in-laboratory testing without training . Training produced large improvements in syllable identification in IT subjects , whereas spontaneous improvement was minimal in DT subjects . DT subjects then underwent training and showed performance improvements comparable with those of the IT group . Training-related improvement in NST scores significantly exceeded improvements due to amplification . In Experiment 2 , experienced HA users received identical training and testing procedures as users in Experiment 1 . The experienced users also showed significant training benefit . Training-related improvements generalized to untrained voices and were maintained on retention tests . Perceptual training appears to be a promising tool for improving speech perception in new and experienced HA users This paper describes the first phase in the development of the Connected Speech Test ( CST ) . This test of intelligibility of everyday speech has been developed primarily for use as a criterion measure in investigations of hearing aid benefit . The test consists of 48 passages of conversationally produced connected speech . Each passage contains 25 key words for scoring . All passages are of equal intelligibility for the average normal hearer . Key words vary in intelligibility within a passage but span the same intelligibility range in all passages . Several passages are administered , and the results averaged , to yield a single intelligibility score . For pairs of scores , each based on mean performance across 4 r and omly-chosen passages , the 95 % critical difference is estimated to be about 14 rationalized arcsine units ( rau ) . The performance-intensity function for the CST has a slope of 12 rau/dB signal-to-babble ratio . Investigations of the test are continuing with hearing-impaired listeners Objectives : The goal of this study was to create and vali date a new set of sentence lists that could be used to evaluate the speech perception abilities of hearing-impaired listeners and cochlear implant ( CI ) users . Our intention was to generate a large number of sentence lists with an equivalent level of difficulty for the evaluation of performance over time and across conditions . Design : The AzBio sentence corpus includes 1000 sentences recorded from two female and two male talkers . The mean intelligibility of each sentence was estimated by processing each sentence through a five-channel CI simulation and calculating the mean percent correct score achieved by 15 normal-hearing listeners . Sentences from each talker were sorted by percent correct score , and 165 sentences were selected from each talker and were then sequentially assigned to 33 lists , each containing 20 sentences ( 5 sentences from each talker ) . List equivalency was vali date d by presenting all lists , in r and om order , to 15 CI users . Results : Using sentence scores from the CI simulation study produced 33 lists of sentences with a mean score of 85 % correct . The results of the validation study with CI users revealed no significant differences in percent correct scores for 29 of the 33 sentence lists . However , individual listeners demonstrated considerable variability in performance on the 29 lists . The binomial distribution model was used to account for the inherent variability observed in the lists . This model was also used to generate 95 % confidence intervals for one and two list comparisons . A retrospective analysis of 172 instances where research subjects had been tested on two lists within a single condition revealed that 94 % of results were accurately contained within these confidence intervals . Conclusions : The use of a five-channel CI simulation to estimate the intelligibility of individual sentences allowed for the creation of a large number of sentence lists with an equivalent level of difficulty . The results of the validation procedure with CI users found that 29 of 33 lists allowed scores that were not statistically different . However , individual listeners demonstrated considerable variability in performance across lists . This variability was accurately described by the binomial distribution model and was used to estimate the magnitude of change required to achieve statistical significance when comparing scores from one and two lists per condition . Fifteen sentence lists have been included in the AzBio Sentence Test for use in the clinical evaluation of hearing-impaired listeners and CI users . An additional eight sentence lists have been included in the Minimum Speech Test Battery to be distributed by the CI manufacturers for the evaluation of CI c and i date BACKGROUND The Revised Speech Perception in Noise Test ( R-SPIN ; Bilger , 1984b ) is composed of 200 target words distributed as the last words in 200 low-predictability ( LP ) and 200 high-predictability ( HP ) sentences . Four list pairs , each consisting of two 50-sentence lists , were constructed with the target word in a LP and HP sentence . Traditionally the R-SPIN is presented at a signal-to-noise ratio ( SNR , S/N ) of 8 dB with the listener task to repeat the last word in the sentence . PURPOSE The purpose was to determine the practicality of altering the R-SPIN format from a single SNR paradigm into a multiple SNR paradigm from which the 50 % points for the HP and LP sentences can be calculated . RESEARCH DESIGN Three repeated measures experiments were conducted . STUDY SAMPLE Forty listeners with normal hearing and 184 older listeners with pure-tone hearing loss participated in the sequence of experiments . DATA COLLECTION AND ANALYSIS The R-SPIN sentences were edited digitally ( 1 ) to maintain the temporal relation between the sentences and babble , ( 2 ) to establish the SNRs , and ( 3 ) to mix the speech and noise signals to obtain SNRs between -1 and 23 dB. All material s were recorded on CD and were presented through an earphone with the responses recorded and analyzed at the token level . For reference purpose s the Words-in-Noise Test ( WIN ) was included in the first experiment . RESULTS In Experiment 1 , recognition performances by listeners with normal hearing were better than performances by listeners with hearing loss . For both groups , performances on the HP material s were better than performances on the LP material s. Performances on the LP material s and on the WIN were similar . Performances at 8 dB S/N were the same with the traditional fixed level presentation and the descending presentation level paradigms . The results from Experiment 2 demonstrated that the four list pairs of R-SPIN material s produced good first approximation psychometric functions over the -4 to 23 dB S/N range , but there were irregularities . The data from Experiment 2 were used in Experiment 3 to guide the selection of the words to be used at the various SNRs that would provide homogeneous performances at each SNR and would produce systematic psychometric functions . In Experiment 3 , the 50 % points were in good agreement for the LP and HP conditions within both groups of listeners . The psychometric functions for List Pairs 1 and 2 , 3 and 4 , and 5 and 6 had similar characteristics and maintained reasonable separations between the HP and LP functions , whereas the HP and LP functions for List Pair 7 and 8 bisected one another at the lower SNRs . CONCLUSIONS This study indicates that the R-SPIN can be configured into a multiple SNR paradigm . A more in-depth study with the R-SPIN material s is needed to develop lists that are systematic and reasonably equivalent for use on listeners with hearing loss . The approach should be based on the psychometric characteristics of the 200 HP and 200 LP sentences with the current R-SPIN lists discarded . Of importance is maintaining the synchrony between the sentences and their accompanying babble BACKGROUND Reduced hearing in elderly people is important because it is disabling and potentially treatable . We aim ed to assess the prevalence of reduced hearing in elderly people and levels of ownership of hearing aids and use . METHODS We have done a cross-sectional survey of people aged at least 75 years in 106 family practice s in the UK . We obtained self-reported data on hearing difficulties for 32,656 people and gave 14,877 a whispered voice test ( response rate 78 % ) . FINDINGS 2537 ( 8 % ) of 32,656 participants reported a lot of difficulty hearing and 13,630 ( 42 % ) a little or a lot of difficulty . 3795 ( 26 % ) of 14877 participants who completed the whispered voice test ( 95 % CI 23 - 29 ) failed the test , the proportion rising sharply with age . Following wax removal , 343 passed a retest , leaving 3452 ( 23 % , 20 - 26 ) who failed the test , even after wax removal if present . 998 ( 46 % ) of 2180 people wearing a hearing aid at the time of testing failed the whispered voice test . More than half the people who failed the test did not own a hearing aid . 2200 ( 60 % ) of 3846 people who owned a hearing aid said they used it regularly . Level of use was strongly related to perceived benefit . INTERPRETATION Reduced hearing is common and provision of hearing aids inadequate in elderly people . Many people who own a hearing aid do not use it regularly , and even when wearing their aid many still have socially disabling levels of hearing loss . A major source of morbidity in elderly people could be alleviated by improvements in detection and management of reduced hearing Objectives : It was hypothesized that auditory training would allow bimodal patients to combine in a better manner the low-frequency acoustic information provided by a hearing aid with the electric information provided by a cochlear implant , thus maximizing the benefit of combining acoustic ( A ) and electric ( E ) stimulation ( EAS ) . Design : Performance in quiet or in the presence of a multitalker babble at + 5 dB signal to noise ratio was evaluated in seven bimodal patients before and after auditory training . The performance measures comprised identification of vowels and consonants , consonant-nucleus-consonant words , sentences , voice gender , and emotion . Baseline performance was evaluated in the A-alone , E-alone , and combined EAS conditions once per week for 3 weeks . A phonetic-contrast training protocol was used to facilitate speech perceptual learning . Patients trained at home 1 hour a day , 5 days a week , for 4 weeks with both their cochlear implant and hearing aid devices on . Performance was remeasured after the 4 weeks of training and 1 month after training stopped . Results : After training , there was significant improvement in vowel , consonant , and consonant-nucleus-consonant word identification in the E and EAS conditions . The magnitude of improvement in the E condition was equivalent to that in the EAS condition . The improved performance was largely retained 1 month after training stopped . Conclusion : Auditory training , in the form administered in this study , can improve bimodal patients ’ overall speech underst and ing by improving E-alone performance Objective : While auditory training in quiet has been shown to improve cochlear implant ( CI ) users ' speech underst and ing in quiet , it is unclear whether training in noise will benefit speech underst and ing in noise . The present study investigated whether auditory training could improve CI users ' speech recognition in noise and whether training with familiar stimuli in an easy listening task ( closed-set digit recognition ) would improve recognition of unfamiliar stimuli in a more difficult task ( open-set sentence recognition ) . Design : CI users ' speech underst and ing in noise was assessed before , during , and after auditory training with a closed-set recognition task ( digits identification ) in speech babble . Before training was begun , recognition of digits , Hearing in Noise Test ( HINT ) sentences , and IEEE sentences presented in steady speech-shaped noise or multitalker speech babble was repeatedly measured to establish a stable estimate of baseline performance . After completing baseline measures , participants trained at home on their personal computers using custom software for approximately 30 mins/day , 5 days/wk , for 4 wks , for a total of 10 hrs of training . Participants were trained only to identify r and om sequences of three digits presented in speech babble , using a closed-set task . During training , the signal-to-noise ratio was adjusted according to subject performance ; auditory and visual feedback was provided . Recognition of digits , HINT sentences , and IEEE sentences in steady noise and speech babble was remeasured after the second and fourth week of training . Training was stopped after the fourth week , and subjects returned to the laboratory 1 mo later for follow-up testing to see whether any training benefits had been retained . Results : Mean results showed that the digit training in babble significantly improved digit recognition in babble ( which was trained ) and in steady noise ( which was not trained ) . The training benefit generalized to improved HINT and IEEE sentence recognition in both types of noise . Training benefits were largely retained in follow-up measures made 1 mo after training was stopped . Conclusions : The results demonstrated that auditory training in noise significantly improved CI users ' speech performance in noise , and that training with simple stimuli using an easy closed-set listening task improved performance with difficult stimuli and a difficult open-set listening task In the Color-Word Stroop test ( CWST ) , the basic task is to name the ink color of rows of XXXs , and performance in this condition is compared with performance in naming the ink-color of color words under conditions where word meanings and ink colors mismatch or are incongruent ( e.g. , the word red printed in green ink ) . The present study investigated whether Stroop test interference , defined as the cost associated with ink-color naming in the incongruous stimulus condition versus in the basic color-naming condition , provides positive evidence for a kind of processing qualitatively different than that which is required for color naming or for word reading . Does the pattern of age-related differences in Stroop interference force the conclusion that the incongruous condition taps a qualitatively different kind of processing than that required for color naming or for word reading ? We gave the CWST to 310 healthy adults . Their performance in each condition of the test replicates and extends previous findings . Structural equation modeling of the data showed a significant , direct link between age and performance in the latent factor associated with the incongruent condition . However , this direct link with age produced a relatively small increase in the model 's fit ; it amounted to only a .024 increase in the proportion of variance explained in the incongruent condition . In light of this small direct influence due to age , the most parsimonious explanation of our findings is that age effects in Stroop interference are due to age-related slowing ( which is also indexed by color naming and by word reading ) primarily ; the findings do not provide evidence for a qualitatively different kind of processing that declines with age Abstract Objective : Our long-term objective is to develop an auditory training program that will enhance speech recognition in those situations where patients most want improvement . As a first step , the current investigation trained participants using either a single talker or multiple talkers to determine if auditory training leads to transfer-appropriate gains . Design : The experiment implemented a 2 × 2 × 2 mixed design , with training condition as a between- participants variable and testing interval and test version as repeated- measures variables . Participants completed a computerized six-week auditory training program wherein they heard either the speech of a single talker or the speech of six talkers . Training gains were assessed with single-talker and multi-talker versions of the Four-choice discrimination test . Participants in both groups were tested on both versions . Study sample : Sixty-nine adult hearing-aid users were r and omly assigned to either single-talker or multi-talker auditory training . Results : Both groups showed significant gains on both test versions . Participants who trained with multiple talkers showed greater improvement on the multi-talker version whereas participants who trained with a single talker showed greater improvement on the single-talker version . Conclusion : Transfer-appropriate gains occurred following auditory training , suggesting that auditory training can be design ed to target specific patient needs . Sumario Objetivo : Nuestro objetivo a largo plazo es desarrollar un programa de entrenamiento auditivo que mejore el reconocimiento del lenguaje en aquellas situaciones en las que los pacientes lo requieran más . Como un primer paso , la investigación actual entrenó a los participantes utiliz and o un solo hablante o múltiples hablantes para determinar si el entrenamiento auditivo logra transferir una ganancia apropiada . Diseño : En el experimento se implementó un dise o mixto 2 × 2 × 2 con las condiciones de entrenamiento como una variable entre los participantes , y los intervalos de evaluación y la versión de la prueba como variables de medidas repetidas . Los participantes completaron un programa de entrenamiento auditivo computarizado de seis semanas en donde oían el discurso de un solo hablante o de seis hablantes . La ganancia lograda por el entrenamiento fue evaluada por medio de la prueba de discriminación de cuatro opciones en la versión de uno y de seis hablantes . Los participantes en ambos grupos fueron evaluados con ambas versiones . Muestra : Sesenta y nueve adultos usuarios de auxiliar auditivo fueron asignados al azar para recibir entrenamiento con uno o con seis hablantes . Result ados : Ambos grupos mostraron una ganancia significativa en ambas versiones de la prueba . Los participantes que se entrenaron con múltiples hablantes mostraron una mayor mejoría en la versión multi-hablantes mientras que los participantes entrenados con un solo hablante mostraron una mejoría mayor en la versión de un solo hablante . Conclusion es : La ganancia correspondiente a la transferencia apropiada ocurrió después del entrenamiento auditivo , lo que sugiere que el entrenamiento auditivo puede ser diseñado para necesidades específicas de los pacientes |
2,168 | 27,597,935 | Flexible sigmoidoscopy ( FS ) prevented CRC and led to the largest reduction in CRC mortality with a smaller but significant reduction in CRC mortality with the use of guaiac fecal occult blood tests ( gFOBTs ) .
There was insufficient or low quality evidence to support the use of other screening tests , including colonoscopy , as well as changing the ages of initiation and cessation for CRC screening with gFOBTs in Ontario .
Either annual or biennial screening using gFOBT reduces CRC-related mortality .
Conclusion .
The evidentiary base supports the use of FS or FOBT ( either annual or biennial ) to screen patients at average risk for CRC . | The objectives of this systematic review were to evaluate the evidence for different CRC screening tests and to determine the most appropriate ages of initiation and cessation for CRC screening and the most appropriate screening intervals for selected CRC screening tests in people at average risk for CRC . | BACKGROUND Screening for colorectal cancer is widely recommended , but the preferred strategy remains unidentified . We aim ed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography . METHODS Members of the general population , aged 50 - 75 years , and living in the regions of Amsterdam or Rotterdam , identified via the registries of the regional municipal administration , were r and omly allocated ( 2:1 ) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography . R and omisation was done per household with a minimisation algorithm based on age , sex , and socioeconomic status . Invitations were sent between June 8 , 2009 , and Aug 16 , 2010 . Participants assigned to CT colonography who were found to have one or more large lesions ( ≥10 mm ) were offered colonoscopy ; those with 6 - 9 mm lesions were offered surveillance CT colonography . The primary outcome was the participation rate , defined as number of invitees undergoing the examination relative to the total number of invitees . Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees . Invitees and screening centre employees were not masked to allocation . This trial is registered in the Dutch trial register , number NTR1829 . FINDINGS 1276 ( 22 % ) of 5924 colonoscopy invitees participated , compared with 982 ( 34 % ) of 2920 CT colonography invitees ( relative risk [ RR ] 1·56 , 95 % CI 1·46 - 1·68 ; p<0·0001 ) . Of the participants in the colonoscopy group , 111 ( 9 % ) had advanced neoplasia of whom seven ( < 1 % ) had a carcinoma . Of CT colonography participants , 84 ( 9 % ) were offered colonoscopy , of whom 60 ( 6 % ) had advanced neoplasia of whom five ( < 1 % ) had a carcinoma ; 82 ( 8 % ) were offered surveillance . The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography ( RR 1·46 , 95 % CI 1·06 - 2·03 ; p=0·02 ) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography ( RR 0·91 , 0·66 - 2·03 ; p=0·56 ) . The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography , respectively ( RR 0·74 , 95 % CI 0·53 - 1·03 ; p=0·07 ) . Serious adverse events related to the screening procedure were post-polypectomy bleedings : two in the colonoscopy group and three in the CT colonography group . INTERPRETATION Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy , but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography . The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies , indicating that both techniques can be used for population -based screening for colorectal cancer . Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable . FUNDING Netherl and s Organisation for Health Research and Development , Centre for Translational Molecular Medicine , and the Nuts Ohra Foundation BACKGROUND & AIMS Data from r and omized controlled trials on the effects of screening colonoscopies on colorectal cancer ( CRC ) incidence and mortality are not available . Observational studies have suggested that colonoscopies strongly reduce the risk of CRC , but there is little specific evidence on the effects of screening colonoscopies . METHODS We performed a population -based case-control study of 3148 patients with a first diagnosis of CRC ( cases ) and 3274 subjects without CRC ( controls ) from the Rhine-Neckar region of Germany from 2003 to 2010 . Detailed information on previous colonoscopy and potential confounding factors was collected by st and ardized personal interviews . Self-reported information on colonoscopies and their indications was vali date d by medical records . We used multiple logistic regression to assess the association between colonoscopy conducted for specific indications within the past 10 years and risk of CRC . RESULTS A history of colonoscopy was associated with a reduced subsequent risk of CRC , independently of the indication for the examination . However , somewhat stronger associations were found for examinations with screening indications ( adjusted odds ratio [ OR ] 0.09 , 95 % confidence interval [ CI ] 0.07 - 0.13 ) than for examinations with diagnostic indications , such as positive fecal occult blood test result ( OR , 0.33 ; 95 % CI , 0.19 - 0.57 ) , surveillance after a preceding colonoscopy ( OR , 0.33 ; 95 % CI , 0.24 - 0.45 ) , rectal bleeding ( OR , 0.28 ; 95 % CI , 0.20 - 0.40 ) , abdominal symptoms ( OR , 0.15 ; 95 % CI , 0.10 - 0.21 ) , or other ( OR , 0.21 ; 95 % CI , 0.14 - 0.30 ) . Colonoscopy was also associated with a reduced risk of cancer in the right colon , regardless of the indication , although to a smaller extent than for other areas of the colon ( OR for screening colonoscopy , 0.22 ; 95 % CI , 0.14 - 0.33 ) . CONCLUSIONS In a population -based case-control study , the risk of CRC was strongly reduced up to 10 years after colonoscopy for any indication . Risk was particularly low after screening colonoscopy , even for cancer in the right colon BACKGROUND In r and omized trials , fecal occult-blood testing reduces mortality from colorectal cancer . However , the duration of the benefit is unknown , as are the effects specific to age and sex . METHODS In the Minnesota Colon Cancer Control Study , 46,551 participants , 50 to 80 years of age , were r and omly assigned to usual care ( control ) or to annual or biennial screening with fecal occult-blood testing . Screening was performed from 1976 through 1982 and from 1986 through 1992 . We used the National Death Index to obtain up date d information on the vital status of participants and to determine causes of death through 2008 . RESULTS Through 30 years of follow-up , 33,020 participants ( 70.9 % ) died . A total of 732 deaths were attributed to colorectal cancer : 200 of the 11,072 deaths ( 1.8 % ) in the annual-screening group , 237 of the 11,004 deaths ( 2.2 % ) in the biennial-screening group , and 295 of the 10,944 deaths ( 2.7 % ) in the control group . Screening reduced colorectal-cancer mortality ( relative risk with annual screening , 0.68 ; 95 % confidence interval [ CI ] , 0.56 to 0.82 ; relative risk with biennial screening , 0.78 ; 95 % CI , 0.65 to 0.93 ) through 30 years of follow-up . No reduction was observed in all-cause mortality ( relative risk with annual screening , 1.00 ; 95 % CI , 0.99 to 1.01 ; relative risk with biennial screening , 0.99 ; 95 % CI , 0.98 to 1.01 ) . The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group ( P=0.04 for interaction ) . CONCLUSIONS The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality . The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy . ( Funded by the Veterans Affairs Merit Review Award Program and others . ) Introduction : We conducted a cluster-r and omized trial aim ed at assessing the effect of the type of faecal occult blood , guaiac or immunochemical test on screening compliance . Methods : We sample d 130 general practitioners ( GPs ) who consented to participate in the trial . We r and omly allocated half of them to the guaiac ( Hemo-Fec ) and half to the immunochemical test ( OC-Hemodia ) . We sample d 2/10 of the GPs ' 50–75-year-old patients ( n=7332 ) and r and omly divided this population into half . One half was invited to be screened at the GP 's office and the other to the nearest gastroenterology ward . The principal outcome was the percentage of returned tests . Results : The immunochemical test had a compliance of 35.8 % and the guaiac of 30.4 % ( relative risk [ RR ] 1.20 ; 95 % confidence interval [ CI ] 1.02–1.44 ) . The difference was mostly due to a higher probability of returning the sample : 93.8 % and 88.6 % for immunochemical and guaiac , respectively ( RR 1.06 ; 95 % CI 1.02–1.10 ) . The guaiac test had a higher prevalence of positives ( 10.3 % versus 6.3 % , RR 0.603 ; 95 % CI 0.433–0.837 ) . There was a higher variability in the results obtained with the guaiac test compared with the immunochemical ( F[1 , 12 ] = 16.25 ; P=0.0017 ) . Conclusions : Compliance is more likely with the immunochemical than the guaiac test , independent of the provider . Guaiac tests show a higher variability of the results among centres . The successful implementation of a screening programme requires a period of st and ardization of the test reading in order to avoid unexpected work overload for colonscopy services BACKGROUND Data on the adherence rate to screening colonoscopy ( OC ) in the average-risk general population are limited and variable . Aim of this study was to compare the uptake of OC screening with that of fecal occult blood ( FOBT ) . METHODS A nationwide , population -based , multicentre , r and omized trial comparing attendance to OC with that to FOBT was performed . Sixty-four general practitioners ( GPs ) , overall including in their lists 9889 average-risk subjects aged 55 - 64 years , were r and omized between OC and FOBT screening programs . Eligible subjects were mailed a personal invitation letter co-signed by their GP and the coordinator of the area-reference GI centre . Attendance rate and detection rate for advanced neoplasia ( colorectal cancer , adenoma > 10 mm or with villous histology or high- grade dysplasia ) for each arm of the study were assessed . RESULTS The overall attendance rate was 18.7 % ( 1563/8378 eligible subjects ) . It was markedly lower in the OC than in the FOBT strategy ( 10 % vs. 27.1 % ; OR 0.28 , 95 % CI : 0.25 - 0.32 ; P<0.0001 ) . In particular , participation in OC screening arm was extremely low in South Italy ( 2.8 % ) , whilst it was higher in North- Central Italy ( 12.4 % ; P<0.0001 ) . Compliance to colonoscopy in those with a positive FOBT was only 58 % . Advanced neoplasia was detected in 28 ( 6.8 % ) patients in the OC arm and in 6 ( 18 % ) in those with a positive FOBT su bmi tted to OC . CONCLUSIONS The results of our study underline the difficulties and barriers to implement a OC population screening in Italy , at least through primary care . Although attendance to FOBT was higher , it was disappointingly less than 30 % . Significant actions to improve awareness amongst GPs and the population are a high priority BACKGROUND : The role of screening colonoscopy for colorectal ( CR ) neoplasia in average-risk population , remains to be determined . OBJECTIVES : To evaluate the prevalence and anatomic location of CR adenoma and carcinoma and the morbidity of colonoscopy in individuals at average risk for CR cancer ( CRC ) . METHODS : A retrospective prevalence study of subjects aged 40–80 yr , with no cancer-related symptoms , personal or family history of CR neoplasia , who underwent a colonoscopy . RESULTS : Enrolled were 1,177 persons ; 183 aged 40–49 yr ( young ) , 917 aged 50–75 yr , and 77 aged 76–80 yr ( elderly ) . The prevalence of overall CR neoplasia , advanced neoplasia , and cancer was 20.9 % , 6.3 % , and 1.1 % , respectively . In the 50–75 age group , the prevalence of overall adenoma , advanced neoplasia , and cancer was 21.3 % , 6.7 % , and 1.2 % , respectively . Of the 206 neoplasia cases , 21–43 % harbored proximal neoplasia beyond the reach of sigmoidoscopy , without distal lesions . Among the elderly , the prevalence of overall adenoma , advanced neoplasia , and cancer reached 26.0 % , 14.3 % , and 2.6 % , respectively . In the young group , 9.8 % had overall neoplasia , 1.1 % had advanced adenoma , and none had CRC . Procedure-related morbidity rate was 0.1 % , with no perforations , bleedings , or mortality . CONCLUSIONS : Screening colonoscopy in average-risk subjects demonstrated a considerable prevalence of CR neoplasia and proximal lesions beyond the reach of sigmoidoscopy . The morbidity rate was negligible . Primary screening colonoscopy should be considered in health programs for the average-risk population , beginning at the age of 50 yr . The significantly high rate of advanced and proximal neoplasia in the elderly , encourages the inclusion of healthy subjects aged 76–80 yr in future prospect i ve studies BACKGROUND Although tests for occult blood in the feces are widely used to screen for colorectal cancers , there is no conclusive evidence that they reduce mortality from this cause . We evaluated a fecal occult-blood test in a r and omized trial and documented its effectiveness . METHODS We r and omly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year , to screening every two years , or to a control group . Participants who were screened su bmi tted six guaiac-impregnated paper slides with two smears from each of three consecutive stools . About 83 percent of the slides were rehydrated . Participants who tested positive underwent a diagnostic evaluation that included colonoscopy . Vital status was ascertained for all study participants during 13 years of follow-up . A committee determined causes of death . A single pathologist determined the stage of each tissue specimen . Differences in mortality from colorectal cancer , the primary study end point , were monitored with the sequential log-rank statistic . RESULTS The 13-year cumulative mortality per 1000 from colorectal cancer was 5.88 in the annually screened group ( 95 percent confidence interval , 4.61 to 7.15 ) , 8.33 in the biennially screened group ( 95 percent confidence interval , 6.82 to 9.84 ) , and 8.83 in the control group ( 95 percent confidence interval , 7.26 to 10.40 ) . The rate in the annually screened group , but not in the biennially screened group , was significantly lower than that in the control group . Reduced mortality in the annually screened group was accompanied by improved survival in those with colorectal cancer and a shift to detection at an earlier stage of cancer . CONCLUSIONS Annual fecal occult-blood testing with rehydration of the sample s decreased the 13-year cumulative mortality from colorectal cancer by 33 percent Objective : This is the first study to evaluate the association between colonic screening and colorectal cancer risk among Canadians . Methods : A case – control study was conducted . Cases were diagnosed with cancer of the colorectum , between 1997 and 2000 , aged 20 to 74 years , identified through the population -based Ontario Cancer Registry and recruited by the Ontario Familial Colorectal Cancer Registry . Controls were a sex- and age-matched r and om sample of the population of Ontario . 971 cases and 1944 controls completed question naires ( including colorectal screening history and many risk factors ) . Multivariate logistic regression analysis was used to obtain adjusted odds ratios ( OR ) estimates . Results : Having had a fecal occult blood screen was associated with reduced colorectal cancer risk ( OR=0.76 ; 95 % confidence interval ( CI ) : 0.59 , 0.97 ) . Having had a screening sigmoidoscopy was associated with a halving of colorectal cancer risk ( OR = 0.52 ; 95 % CI : 0.34 , 0.80 ) . Having had a screening colonoscopy did not significantly reduce colorectal cancer risk ( OR = 0.69 ; 95 % CI : 0.44 , 1.07 ) ; however , having had either screening endoscopy was associated with a significant reduction in colorectal cancer risk ( OR = 0.62 ; 95 % CI : 0.44 , 0.87 ) . Findings differed slightly by anatomic sub-site ( proximal and distal colorectum ) . Conclusions : We report a reduction in colorectal cancer risk among persons who underwent colorectal cancer screening ; in particular , sigmoidoscopy . Findings are of great importance for the prevention of colorectal cancer BACKGROUND Flexible sigmoidoscopy ( FS ) has been recommended as a screening method to reduce mortality from colorectal cancer ( CRC ) . The present study evaluates the effect of adding FS to the fecal occult blood test Hemoccult-II ( H-II ) on diagnostic yield of colorectal neoplasia . METHODS A total of 10,978 normal persons aged 50 - 75 years were invited to participate , 5495 persons being allocated at r and om to H-II and FS and 5483 to H-II alone . RESULTS In spite of a lower compliance ( 40 % versus 56 % ) for the combined procedure , the diagnostic yield of colorectal neoplasia was higher than for H-II alone ( 12 CRC versus 4 CRC , and 72 large adenomas versus 14 ) . Within 24 - 62 months after screening there were fewer CRCs detected after H-II + FS than after H-II alone . The stage distribution was less favorable than in screen-detected cases . CONCLUSION One FS may not be an optimal way of screening , but FS deserves to be evaluated in r and omized population studies including repeated H-II tests in the control arm Immunochemical fecal occult blood test ( FIT ) is a new colorectal cancer ( CRC ) screening method already recommended by the American screening guidelines . We aim ed to test the feasibility of FIT as compared to guaiac fecal occult blood test ( G‐FOBT ) in a large urban population of Tel Aviv . Average‐risk persons , aged 50–75 years , were offered FIT or G‐FOBT after r and omization according to the socioeconomic status of their clinics . Participants with positive tests underwent colonoscopy . Participants were followed through the Cancer Registry 2 years after the study . Hemoccult SENSA ™ and OC‐MICRO ™ ( three sample s , 70 ng/ml threshold ) were used . FIT was offered to 4,657 persons ( Group A ) and G‐FOBT to 7,880 persons ( Group B ) . Participation rate was 25.9 % and 28.8 % in Group A and B , respectively ( p < 0.001 ) . Positivity rate in Group A and B was 12.7 % and 3.9 % , respectively ( p < 0.001 ) . Cancer found in six ( 0.49 % ) and eight ( 0.35 % ) patients of Group A and B , respectively ( NS ) . Cancer registry follow‐up found missed cancer in five ( 0.22 % ) cases of Group B and none in Group A ( NS ) . The sensitivity , specificity , negative and positive predictive value for cancer in Group A and B were 100 % , 85.9 % , 100 % , 3.9 % and 61.5 % , 96.4 % , 99.8 % , 9.1 % , respectively . There was increased detection of advanced adenomatous polyp ( AAP ) by FIT , irrespective of age , gender , and socioeconomic status ( Per Protocol : odds ratio 2.69 , 95 % confidence interval 1.6–4.5 ; Intention to Screen : odds ratio 3.16 , 95 % confidence interval 1.8–5.4 ) . FIT is feasible in urban , average‐risk population , which significantly improved performance for detection of AAP and CRC , despite reduced participation PURPOSE Three-year disease-free survival ( DFS ) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin ( LV5FU2 ) with the addition of oxaliplatin ( FOLFOX4 ) . Final results of the study , including 6-year overall survival ( OS ) and 5-year up date d DFS , are reported . PATIENTS AND METHODS A total of 2,246 patients were r and omly assigned to receive LV5FU2 or FOLFOX4 for 6 months . The primary end point was DFS . Secondary end points were OS and safety . Results Five-year DFS rates were 73.3 % and 67.4 % in the FOLFOX4 and LV5FU2 groups , respectively ( hazard ratio [ HR ] = 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .003 ) . Six-year OS rates were 78.5 % and 76.0 % in the FOLFOX4 and LV5FU2 groups , respectively ( HR = 0.84 ; 95 % CI , 0.71 to 1.00 ; P = .046 ) ; corresponding 6-year OS rates for patients with stage III disease were 72.9 % and 68.7 % , respectively ( HR = 0.80 ; 95 % CI , 0.65 to 0.97 ; P = .023 ) . No difference in OS was seen in the stage II population . The incidence of second noncolorectal cancers was 5.5 % and 6.1 % in the FOLFOX4 and LV5FU2 groups , respectively . Among patients receiving oxaliplatin , the frequency of grade 3 peripheral sensory neuropathy was 1.3 % 12 months after treatment and 0.7 % at 48 months . CONCLUSION Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease BACKGROUND Colonoscopy with a possible polypectomy is an efficient and preferred screening method to reduce the incidence of colorectal cancer ( CRC ) . However , critics argue that , to date , a reduction of incidence and mortality from CRC has not been demonstrated in a population -based setting . OBJECTIVE To compare the incidence of and mortality from CRC among individuals screened by colonoscopy and non-screened individuals . DESIGN A closed cohort study . SETTING Population -based setting in a precisely defined area with a low level of population migration . PATIENTS This study involved 1912 screened and 20,774 control participants . INTERVENTION CRC cases in this closed cohort study were prospect ively collected during the screening period of 1 year and the follow-up period of 6 years . MAIN OUTCOME MEASUREMENTS Follow-up data were corrected for negligible migration balance in the area . Tumor characteristics and risk or protective factors , age and sex , participation in general health screening examinations , history of CRC in a first-degree relative , smoking status , body mass index , frequency of sports activity , eating habits , and patients ' professions were recorded . RESULTS Overall cancer incidence was significantly lower in the screened group compared with the non-screened group ( adjusted odds ratio [ OR ] 0.31 ; 95 % confidence interval [ CI ] , 0.16 - 0.59 ; P < .001 ) . Colon cancer-associated mortality also was clearly lower ( adjusted OR 0.12 ; 95 % CI , 0.01 - 0.93 ; P = .04 ) . Risk factors such as lifestyle , smoking , and body mass index as well as family history were similar in both groups . Blue-collar workers had a higher incidence of CRC compared with professionals . The risk factors for CRC were a positive family history and smoking . LIMITATIONS Number and ethnicity of the participants , non-r and omized study . CONCLUSION Colonoscopy with polypectomy significantly reduces CRC incidence and cancer-related mortality in the general population BACKGROUND A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer ( CRC ) screening . METHODS We conducted a r and omized controlled trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality . A question naire to assess the eligibility and interest in screening was mailed to 236,568 men and women , aged 55 - 64 years , who were r and omly selected from six trial centers in Italy . Of the 56,532 respondents , interested and eligible subjects were r and omly assigned to the intervention group ( invitation for flexible sigmoidoscopy ; n = 17,148 ) or the control group ( no further contact ; n = 17,144 ) , between June 14 , 1995 , and May 10 , 1999 . Flexible sigmoidoscopy was performed on 9911 subjects . Intention-to-treat and per- protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups . Per- protocol analysis was adjusted for noncompliance . RESULTS A total of 34,272 subjects ( 17,136 in each group ) were included in the follow-up analysis . The median follow-up period was 10.5 years for incidence and 11.4 years for mortality ; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group . Overall incidence rates in the intervention and control groups were 144.11 and 176.43 , respectively , per 100,000 person-years . CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group . Mortality rates in the intervention and control groups were 34.66 and 44.45 , respectively , per 100,000 person-years . In the intention-to-treat analysis , the rate of CRC incidence was statistically significantly reduced in the intervention group by 18 % ( rate ratio [ RR ] = 0.82 , 95 % confidence interval [ CI ] = 0.69 to 0.96 ) , and the mortality rate was non-statistically significantly reduced by 22 % ( RR = 0.78 ; 95 % CI = 0.56 to 1.08 ) compared with the control group . In the per- protocol analysis , both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects ; CRC incidence was reduced by 31 % ( RR = 0.69 ; 95 % CI = 0.56 to 0.86 ) and mortality was reduced by 38 % ( RR = 0.62 ; 95 % CI = 0.40 to 0.96 ) compared with the control group . CONCLUSION A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality BACKGROUND This r and omised controlled trial is examining the hypothesis that a single flexible sigmoidoscopy screening offered at around age 60 years can lower the incidence and mortality of colorectal cancer . We report here on acceptability , safety , feasibility , and yield . METHODS Men and women aged 55 - 64 years , in 14 UK centres , who responded to a mailed question naire that they would attend for flexible sigmoidoscopy screening if invited , were r and omly assigned screening or control ( ratio one to two ) . The control group was not contacted . Small polyps were removed during screening , and colonoscopy was undertaken if high-risk polyps ( three or more adenomas , size 1 cm or greater , villous , severely dysplastic , or malignant ) were found . FINDINGS Of 354,262 people asked about their interest in having flexible sigmoidoscopy screening , 194,726 ( 55 % ) responded positively , and 170,432 eligible individuals were r and omised . Attendance among those assigned screening was 71 % ( 40,674 of 57,254 ) . 2131 ( 5 % ) were classified as high-risk and referred for colonoscopy ; 38,525 with no polyps or only low-risk polyps detected were discharged . Distal adenomas were detected in 4931 ( 12.1 % ) and distal cancer in 131 ( 0.3 % ) . Proximal adenomas were detected in 386 ( 18.8 % of those undergoing colonoscopy ) and proximal cancer in nine cases ( 0.4 % ) . 62 % of cancers were Dukes ' stage A or locally excised . There was one perforation after flexible sigmoidoscopy and four after colonoscopy . An average of 48 people were screened , and two or three colonoscopy referrals generated , per centre each week . Interpretation Our flexible sigmoidoscopy screening regimen is acceptable , feasible , and safe . The prevalence of neoplasia is high , and colonoscopy referral rates of 5 % are acceptable OBJECTIVES Determine whether colorectal cancer screening adherence is greater with fecal immunochemical tests ( FIT ) or guaiac-based fecal occult blood tests ( gFOBT ) . METHODS We used electronic health records to identify 3869 New Mexico Veterans Affairs Health Care System primary care patients due for screening in 2008 for whom fecal blood testing was appropriate . We invited r and omly selected patients by mail to participate in a study comparing FIT and gFOBT . We r and omly allocated 404 subjects to receive FIT ( n=202 ) or gFOBT ( n=202 ) by mail . We determined the proportion of subjects completing testing within 90days of agreeing to participate in the study . We also used multivariate logistic regression to evaluate screening completion , adjusting for age , gender , race/ethnicity , clinic site , previous gFOBT testing , and co-morbidity . RESULTS Screening adherence was higher with FIT than gFOBT ( 61.4 % vs. 50.5 % , P=0.03 ) . The adjusted odds ratio for completing FIT vs. gFOBT was 1.56 , 95 % CI 1.04 , 2.32 . CONCLUSION In a clinic setting of patients who were due for colorectal cancer screening , adherence was significantly higher with FIT than gFOBT Background As screening methods for colorectal cancer ( CRC ) are limited by uptake and adherence , further options are sought . A blood test might increase both , but none has yet been tested in a screening setting . Objective We prospect ively assessed the accuracy of circulating methylated SEPT9 DNA ( mSEPT9 ) for detecting CRC in a screening population . Design Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma sample s before colon preparation . Using a commercially available assay , three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified r and om sample of other subjects in duplicate real time PCRs . The primary outcomes measures were st and ardised for overall sensitivity and specificity estimates . Results 7941 men ( 45 % ) and women ( 55 % ) , mean age 60 years , enrolled . Results from 53 CRC cases and from 1457 subjects without CRC yielded a st and ardised sensitivity of 48.2 % ( 95 % CI 32.4 % to 63.6 % ; crude rate 50.9 % ) ; for CRC stages I – IV , values were 35.0 % , 63.0 % , 46.0 % and 77.4 % , respectively . Specificity was 91.5 % ( 95 % CI 89.7 % to 93.1 % ; crude rate 91.4 % ) . Sensitivity for advanced adenomas was low ( 11.2 % ) . Conclusions Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening . However , the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas . Clinical Trial Registration Number : BACKGROUND In 1993 , a r and omized controlled trial in Minnesota showed , after 13 years of follow-up , that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at least 33 % . Biennial screening ( i.e. , every 2 years ) result ed in only a 6 % mortality reduction . Two European trials ( in Engl and and in Denmark ) subsequently showed statistically significant 15 % and 18 % mortality reductions with biennial screening . Herein , we provide up date d results -through 18 years of follow-up -- from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening . METHODS From 1976 through 1977 , a total of 46551 study subjects , aged 50 - 80 years , were recruited and r and omly assigned to an annual screen , a biennial screen , or a control group . A screen consisted of six guaiac-impregnated fecal occult blood tests ( Hemoccult ) prepared in pairs from each of three consecutive fecal sample s. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy . All participants were followed annually to ascertain incident colorectal cancers and deaths . RESULTS The numbers of deaths from all causes were similar among the three study groups . Cumulative 18-year colorectal cancer mortality was 33 % lower in the annual group than in the control group ( rate ratio , 0.67 ; 95 % confidence interval [ CI ] = 0.51 - 0.83 ) . The biennial group had a 21 % lower colorectal cancer mortality rate than the control group ( rate ratio , 0.79 ; 95 % CI = 0.62 - 0.97 ) . A marked reduction was also noted in the incidence of Dukes ' stage D cancers in both screened groups in comparison with the control group . CONCLUSION The results from this study , together with the other two published r and omized trials of fecal occult blood screening , are consistent in demonstrating a substantial , statistically significant reduction in colorectal cancer mortality from biennial screening BACKGROUND Colorectal cancer is the third most common cancer worldwide and has a high mortality rate . We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality . METHODS This r and omised controlled trial was undertaken in 14 UK centres . 170 432 eligible men and women , who had indicated on a previous question naire that they would accept an invitation for screening , were r and omly allocated to the intervention group ( offered flexible sigmoidoscopy screening ) or the control group ( not contacted ) . R and omisation by sequential number generation was done central ly in blocks of 12 , with stratification by trial centre , general practice , and household type . The primary outcomes were the incidence of colorectal cancer , including prevalent cases detected at screening , and mortality from colorectal cancer . Analyses were intention to treat and per protocol . The trial is registered , number IS RCT N28352761 . FINDINGS 113 195 people were assigned to the control group and 57 237 to the intervention group , of whom 112 939 and 57 099 , respectively , were included in the final analyses . 40 674 ( 71 % ) people underwent flexible sigmoidoscopy . During screening and median follow-up of 11.2 years ( IQR 10.7 - 11.9 ) , 2524 participants were diagnosed with colorectal cancer ( 1818 in control group vs 706 in intervention group ) and 20 543 died ( 13 768 vs 6775 ; 727 certified from colorectal cancer [ 538 vs 189 ] ) . In intention-to-treat analyses , colorectal cancer incidence in the intervention group was reduced by 23 % ( hazard ratio 0.77 , 95 % CI 0.70 - 0.84 ) and mortality by 31 % ( 0.69 , 0.59 - 0.82 ) . In per- protocol analyses , adjusting for self- selection bias in the intervention group , incidence of colorectal cancer in people attending screening was reduced by 33 % ( 0.67 , 0.60 - 0.76 ) and mortality by 43 % ( 0.57 , 0.45 - 0.72 ) . Incidence of distal colorectal cancer ( rectum and sigmoid colon ) was reduced by 50 % ( 0.50 , 0.42 - 0.59 ; secondary outcome ) . The numbers needed to be screened to prevent one colorectal cancer diagnosis or death , by the end of the study period , were 191 ( 95 % CI 145 - 277 ) and 489 ( 343 - 852 ) , respectively . INTERPRETATION Flexible sigmoidoscopy is a safe and practical test and , when offered only once between ages 55 and 64 years , confers a substantial and longlasting benefit . FUNDING Medical Research Council , National Health Service R&D , Cancer Research UK , KeyMed BACKGROUND A single sigmoidoscopy examination at around age 60 years has been proposed as a cost-effective strategy to prevent colorectal cancer . A multicenter r and omized controlled trial , the SCORE trial , is in progress in Italy to estimate the impact of this strategy on colorectal cancer incidence and mortality and the duration of the protective effect . We present the baseline screening outcomes . METHODS A question naire was mailed to a r and om sample of 236 568 people aged 55 - 64 years to assess their eligibility for and interest in screening . Those reporting a history of colorectal cancer , adenomas , inflammatory bowel disease , recent colorectal endoscopy , or two first-degree relatives with colorectal cancer were excluded . Eligible , interested respondents were assigned r and omly to the control group ( no further contact ) or the intervention group ( invitation to undergo sigmoidoscopy ) . Screenees with colorectal cancer , polyps larger than 5 mm , three or more adenomas , adenomas 5 mm or smaller with a villous component of more than 20 % , or severe dysplasia were referred for colonoscopy . RESULTS Of the 56 532 respondents ( 23.9 % of those invited ) , 34 292 were enrolled and 17 148 were assigned to the screening group . Of those , 9999 attended and 9911 were actually examined by sigmoidoscopy . Distal adenomas were detected in 1070 subjects ( 10.8 % ) . Proximal adenomas were detected in 116 of 747 ( 15.5 % ) subjects without cancer at sigmoidoscopy who then underwent colonoscopy . A total of 54 subjects was found to have colorectal cancer , a rate of 5.4 per 1000 ( 54 % of which were Dukes ' A ) . The procedures were relatively safe , with two perforations ( one in 9911 sigmoidoscopy exams and one in 775 colonoscopies ) and one hemorrhage requiring hospitalization after polypectomy during colonoscopy . The pain associated with sigmoidoscopy was described as mild or less than expected by 83.3 % of the screenees . CONCLUSION Sigmoidoscopy screening is generally acceptable to recipients and safe . The high yield of advanced adenomas is consistent with the projected impact of sigmoidoscopy screening on colorectal cancer incidence Objective To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy . Design R and omised controlled trial . Setting Population based screening in two areas in Norway — city of Oslo and Telemark county ( urban and mixed urban and rural population s ) . Participants 55 736 men and women aged 55 - 64 years . Intervention Once only flexible sigmoidoscopy screening with or without a single round of faecal occult blood testing ( n=13 823 ) compared with no screening ( n=41 913 ) . Main outcome measures Planned end points were cumulative incidence and mortality of colorectal cancer after 5 , 10 , and 15 years . This first report from the study presents cumulative incidence after 7 years of follow-up and hazard ratio for mortality after 6 years . Results No difference was found in the 7 year cumulative incidence of colorectal cancer between the screening and control groups ( 134.5 v 131.9 cases per 100 000 person years ) . In intention to screen analysis , a trend towards reduced colorectal cancer mortality was found ( hazard ratio 0.73 , 95 % confidence interval 0.47 to 1.13 , P=0.16 ) . For attenders compared with controls , a statistically significant reduction in mortality was apparent for both total colorectal cancer ( hazard ratio 0.41 , 0.21 to 0.82 , P=0.011 ) and rectosigmoidal cancer ( 0.24 , 0.08 to 0.76 , P=0.016 ) . Conclusions A reduction in incidence of colorectal cancer with flexible sigmoidoscopy screening could not be shown after 7 years ’ follow-up . Mortality from colorectal cancer was not significantly reduced in the screening group but seemed to be lower for attenders , with a reduction of 59 % for any location of colorectal cancer and 76 % for rectosigmoidal cancer in per protocol analysis , an analysis prone to selection bias . Trial registration Clinical trials NCT00119912 Background Screening colonoscopy effectiveness is hampered by limited adherence by the general population . The present prospect i ve study was performed to evaluate whether adding capsule colonoscopy to the endoscopic screening options increases uptake . Methods Invitation letters were sent to 2150 persons above the age of 55 insured with a German medical insurance company in the area of Rinteln , Lower Saxony with a baseline spontaneous annual screening colonoscopy uptake of 1 % . Both capsule or conventional colonoscopy were offered . Interested persons were given information about the two screening options by four local gastroenterologists and examinations were then performed according to screenees ’ final choice . Results 154 persons sought further information , and 34 and 90 underwent conventional and capsule colonoscopy , respectively . Colonoscopy uptake was thus increased by the invitation process by 60 % ( 1.6 % vs. 1 % ; p = 0.075 ) , while the option of capsule endoscopy led to a fourfold increase of screening uptake ( 4.2 % vs. 1 % , p < 0.001 ) . Despite similar age distribution in both sex groups , uptake in men was significantly higher ( 5.6 % vs. 2.8 % , p = 002 ) . However , overall adenoma yield was not different in both groups . Conclusions The present study suggests that offering the option of capsule colonoscopy increases uptake of endoscopic colorectal cancer screening . However , capsule endoscopy sensitivity for adenoma detection needs to be improved BACKGROUND The benefits of endoscopic testing for colorectal-cancer screening are uncertain . We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality . METHODS From 1993 through 2001 , we r and omly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy , with a repeat screening at 3 or 5 years , or to usual care . Cases of colorectal cancer and deaths from the disease were ascertained . RESULTS Of the 77,445 participants r and omly assigned to screening ( intervention group ) , 83.5 % underwent baseline flexible sigmoidoscopy and 54.0 % were screened at 3 or 5 years . The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group ( 1012 cases ) , as compared with 15.2 cases per 10,000 person-years in the usual-care group ( 1287 cases ) , which represents a 21 % reduction ( relative risk , 0.79 ; 95 % confidence interval [ CI ] , 0.72 to 0.85 ; P<0.001 ) . Significant reductions were observed in the incidence of both distal colorectal cancer ( 479 cases in the intervention group vs. 669 cases in the usual-care group ; relative risk , 0.71 ; 95 % CI , 0.64 to 0.80 ; P<0.001 ) and proximal colorectal cancer ( 512 cases vs. 595 cases ; relative risk , 0.86 ; 95 % CI , 0.76 to 0.97 ; P=0.01 ) . There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group ( 252 deaths ) , as compared with 3.9 per 10,000 person-years in the usual-care group ( 341 deaths ) , which represents a 26 % reduction ( relative risk , 0.74 ; 95 % CI , 0.63 to 0.87 ; P<0.001 ) . Mortality from distal colorectal cancer was reduced by 50 % ( 87 deaths in the intervention group vs. 175 in the usual-care group ; relative risk , 0.50 ; 95 % CI , 0.38 to 0.64 ; P<0.001 ) ; mortality from proximal colorectal cancer was unaffected ( 143 and 147 deaths , respectively ; relative risk , 0.97 ; 95 % CI , 0.77 to 1.22 ; P=0.81 ) . CONCLUSIONS Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence ( in both the distal and proximal colon ) and mortality ( distal colon only ) . ( Funded by the National Cancer Institute ; PLCO Clinical Trials.gov number , NCT00002540 . ) BACKGROUND An accurate , noninvasive test could improve the effectiveness of colorectal-cancer screening . METHODS We compared a noninvasive , multitarget stool DNA test with a fecal immunochemical test ( FIT ) in persons at average risk for colorectal cancer . The DNA test includes quantitative molecular assays for KRAS mutations , aberrant NDRG4 and BMP3 methylation , and β-actin , plus a hemoglobin immunoassay . Results were generated with the use of a logistic-regression algorithm , with values of 183 or more considered to be positive . FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive . Tests were processed independently of colonoscopic findings . RESULTS Of the 9989 participants who could be evaluated , 65 ( 0.7 % ) had colorectal cancer and 757 ( 7.6 % ) had advanced precancerous lesions ( advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension ) on colonoscopy . The sensitivity for detecting colorectal cancer was 92.3 % with DNA testing and 73.8 % with FIT ( P=0.002 ) . The sensitivity for detecting advanced precancerous lesions was 42.4 % with DNA testing and 23.8 % with FIT ( P<0.001 ) . The rate of detection of polyps with high- grade dysplasia was 69.2 % with DNA testing and 46.2 % with FIT ( P=0.004 ) ; the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4 % and 5.1 % , respectively ( P<0.001 ) . Specificities with DNA testing and FIT were 86.6 % and 94.9 % , respectively , among participants with nonadvanced or negative findings ( P<0.001 ) and 89.8 % and 96.4 % , respectively , among those with negative results on colonoscopy ( P<0.001 ) . The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy , 166 with DNA testing , and 208 with FIT . CONCLUSIONS In asymptomatic persons at average risk for colorectal cancer , multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results . ( Funded by Exact Sciences ; Clinical Trials.gov number , NCT01397747 . ) BACKGROUND Although there is general consensus concerning the efficacy of colorectal cancer screening , there is a lack of agreement about which routine screening strategy should be adopted . We compared the participation and detection rates achievable through different strategies of colorectal cancer screening . METHODS From November 1999 through June 2001 we conducted a multicenter , r and omized trial in Italy among a sample of 55 - 64 year olds in the general population who had an average risk of colorectal cancer . People with previous colorectal cancer , adenomas , inflammatory bowel disease , a recent ( < or = 2 years ) colorectal endoscopy or fecal occult blood test ( FOBT ) , or two first-degree relatives with colorectal cancer were excluded . Eligible subjects were r and omly assigned , within the roster of their general practitioner , to 1 ) biennial FOBT ( delivered by mail ) , 2 ) biennial FOBT ( delivered by general practitioner or a screening facility ) , 3 ) patient 's choice of FOBT or " once-only " sigmoidoscopy , 4 ) " once-only " sigmoidoscopy , or 5 ) sigmoidoscopy followed by biennial FOBT . An immunologic FOBT was used . Participation and detection rates of the strategies tested were compared using multivariable logistic regression models that adjusted for age , sex , and screening center . All statistical tests were two-sided . RESULTS Of 28 319 people sample d , 1637 were excluded and 26 682 were r and omly assigned to a screening arm . After excluding undelivered letters ( n = 427 ) , the participation rates for groups 1 , 2 , 3 , 4 , and 5 were 30.1 % ( 682/2266 ) , 28.1 % ( 1654/5893 ) , 27.1 % ( 970/3579 ) , 28.1 % ( 1026/3650 ) , and 28.1 % ( 3049/10 867 ) , respectively . Of the 2858 subjects screened by FOBT , 122 ( 4.3 % ) had a positive test result , 10 ( 3.5 per 1000 ) had colorectal cancer , and 39 ( 1.4 % ) had an advanced adenoma . Among the 4466 subjects screened by sigmoidoscopy , 341 ( 7.6 % ) were referred for colonoscopy , 18 ( 4 per 1000 ) had colorectal cancer , and 229 ( 5.1 % ) harbored an advanced adenoma . CONCLUSIONS The participation rates were similar for sigmoidoscopy and FOBT . The detection rate for advanced neoplasia was three times higher following screening by sigmoidoscopy than by FOBT BACKGROUND R and omized controlled trials of sufficient power testing the long-term effect of screening for colorectal neoplasia only exist for faecal occult blood testing ( FOBT ) . There is indirect evidence that flexible sigmoidoscopy ( FS ) may have a greater yield . The aim of this study was to determine the diagnostic yield of screening with FS or a combination of FS and FOBT in an average-risk population in an urban and combined urban and rural population in Norway . METHODS 20,780 men and women ( 1:1 ) , aged 50 - 64 years , were invited for once-only screening ( FS only or a combination of FS and FOBT ( 1:1 ) ) by r and omization from the population registry . A positive FS was defined as a finding of any neoplasia or any polyp > or = 10 mm . A positive FS or FOBT qualified for colonoscopy . RESULTS Overall attendance was 65 % . Forty-one ( 0.3 % ) cases of CRC were detected . Any adenoma was found in 2208 ( 17 % ) participants and 545 ( 4.2 % ) had high-risk adenomas . There was no difference in diagnostic yield between the FS and the FS and FOBT group regarding CRC or high-risk adenoma . Work-up load comprised 2821 colonoscopies in 2524 ( 20 % ) screenees and 10 % of screenees were recommended later colonoscopy surveillance . There were no severe complications at FS , but six perforations after therapeutic colonoscopy ( 1:336 ) . CONCLUSIONS The present study bodes well for future management of a national screening programme , provided that follow-up results reflect adequate proof of a net benefit . It is highly question able whether the addition of once-only FOBT to FS will contribute to this effect AIMS To determine the harm that ensues from faecal occult blood ( FOB ) screening for colorectal cancer . METHODS 150 251 people were r and omly allocated either to receive biennial Haemoccult FOB tests ( n = 75 253 ) or not to be contacted ( n=74 998 ) . Study group patients returning positive tests were offered colonic investigation ; 1774 underwent complete investigation of the colon . RESULTS There was no significant difference in the stage at presentation of interval versus control group cancers . Survival in the interval cancer group was significantly prolonged compared with the control group . Sensitivity for colonoscopy or flexible sigmoidoscopy and double contrast barium enema ( DCBE ) was 96.7 % . There were no complications of DCBE but seven ( 0.5 % ) complications of colonoscopy , of which six required surgical intervention . There were no colonoscopy related deaths . No patients without colorectal cancer died within 30 days of colonic investigation . Five patients died within 30 days of surgery for screen detected colorectal neoplasia and a further two died without having surgery . Six patients died after 30 days but within two years of surgery for screen detected benign adenomas or stage A cancers ; in all cases the cause of death was not related to colorectal cancer . CONCLUSIONS There was investigation related morbidity but no mortality and little to support overdiagnosis bias . The group returning falsely negative tests had a better outcome compared with the whole control group . There is a negative side to any screening programme but mortality reduction in this and other trials suggests that a national programme of colorectal cancer screening should be given consideration BACKGROUND AND PURPOSE : In an ongoing r and omized screening study of 68,306 patients for early detection of colorectal neoplasm , those with positive Hemoccult II ® tests ( Smith Kline Diagnostic , Sunnyvale , CA ) were examined with a flexible sigmoidoscope ( FS ; 60 cm ) and doublecontrast barium enema ( DCE ) . The aim of this study was to determine the rate of complications to the work-up . METHODS : A total of 2,108 FS , 1,987 DCE , 190 colonoscopies , and 104 laparotomies were performed because of a positive Hemoccult ® . RESULTS : One patient 's large bowel was perforated during diagnostic endoscopy . Four perforations of the large bowel occurred during endoscopic polypectomy ( 0.8 percent of 513 adenomas removed ) , and one case of bleeding occurred 12 days after polypectomy . No complications occurred in connection with the 1,987 DCE . Five of 104 laparotomized patients underwent relaparotomy , 3 after removal of a colorectal carcinoma , and 2 of 4 patients with diverticular disease . All five patients healed but required a longer stay at the hospital . CONCLUSIONS : Complications occurred in 0.3 percent of the endoscopies , and 5 percent of patients had to undergo laparotomy again . No mortality occurred . If mortality attributable to colorectal cancer will decrease because of screening , we find the complication rate is acceptable Background Published data suggest that screening might reduce the mortality rate from colorectal neoplasia . Faecal occult blood ( FOB ) testing suffers from poor sensitivity and significant numbers of interval cancers , both of which should be improved by the addition of flexible sigmoidoscopy ( FOS ) BACKGROUND The efficacy of colorectal cancer screening has been proved , and three different screening tests are recommended by international guidelines : the faecal occult blood test , flexible sigmoidoscopy and colonoscopy . While the effectiveness of a screening program depends on the compliance obtained , the role of the type of test on compliance has not yet been sufficiently studied . AIMS To measure the effect of the type of screening test used , i.e. faecal occult blood test or flexible sigmoidoscopy , on the compliance to colorectal cancer screening programs . SUBJECTS AND METHODS A cluster-r and omized two-arm trial was conducted . We r and omly assigned 20 GP 's practice s that had an average of 150 patients between 50 and 74 years old . RESULTS 1449 individuals were referred to faecal occult blood test and 1538 to flexible sigmoidoscopy . The faecal occult blood test obtained higher compliance : 17.2 % ( 95%CI 12.5 - 25.7 ) versus 7.0 % ( 95%CI 5.7 - 9.0 ) . The socio-economic status was an effect modifier of the test type : the effect of the type of test was smaller in low socioeconomic classes . CONCLUSIONS The type of screening test used for colorectal cancer is a determinant of participation . In a low compliance area , better compliance will result from offering the faecal occult blood test than from the flexible sigmoidoscopy BACKGROUND Although fecal occult-blood testing is the only available noninvasive screening method that reduces the risk of death from colorectal cancer , it has limited sensitivity . We compared an approach that identifies abnormal DNA in stool sample s with the Hemoccult II fecal occult-blood test in average-risk , asymptomatic persons 50 years of age or older . METHODS Eligible subjects su bmi tted one stool specimen for DNA analysis , underwent st and ard Hemoccult II testing , and then underwent colonoscopy . Of 5486 subjects enrolled , 4404 completed all aspects of the study . A subgroup of 2507 subjects was analyzed , including all those with a diagnosis of invasive adenocarcinoma or advanced adenoma plus r and omly chosen subjects with no polyps or minor polyps . The fecal DNA panel consisted of 21 mutations . RESULTS The fecal DNA panel detected 16 of 31 invasive cancers , whereas Hemoccult II identified 4 of 31 ( 51.6 percent vs. 12.9 percent , P=0.003 ) . The DNA panel detected 29 of 71 invasive cancers plus adenomas with high- grade dysplasia , whereas Hemoccult II identified 10 of 71 ( 40.8 percent vs. 14.1 percent , P<0.001 ) . Among 418 subjects with advanced neoplasia ( defined as a tubular adenoma at least 1 cm in diameter , a polyp with a villous histologic appearance , a polyp with high- grade dysplasia , or cancer ) , the DNA panel was positive in 76 ( 18.2 percent ) , whereas Hemoccult II was positive in 45 ( 10.8 percent ) . Specificity in subjects with negative findings on colonoscopy was 94.4 percent for the fecal DNA panel and 95.2 percent for Hemoccult II . CONCLUSIONS Although the majority of neoplastic lesions identified by colonoscopy were not detected by either noninvasive test , the multitarget analysis of fecal DNA detected a greater proportion of important colorectal neoplasia than did Hemoccult II without compromising specificity Abstract Objectives : To compare the feasibility of mass screening by flexible sigmoidoscopy with screening by faecal occult blood testing ( Haemoccult ) and both tests combined . Design : Patients were r and omised to screening by flexible sigmoidoscopy , faecal blood testing , or both tests . The flexible sigmoidoscopy examinations were performed by a general practitioner . Setting : General practice . Subjects : 3744 patients aged 50 - 75 years . Main outcome measures : Uptake , positive results , detection of neoplasia , complications , and recall for diagnostic colonoscopy . Results : Uptake was significantly higher in the flexible sigmoidoscopy group ( 46.6 % ) than in the faecal blood test group ( 31.6 % ; P<0.001 ) or than in the group having both tests ( 30.1 % ; P<0.001 ) . Telephone reminders increased uptake of sigmoidoscopy to 61.8 % . In total , 1116 sigmoidoscopy examinations were performed without major complication . Polyps were found in 19.3 % ( 95 % confidence interval 17.0 % to 21.6 % ) but only 6.8 % ( 5.3 % to 8.3 % ) had adenomas and 2.4 % ( 1.5 % to 3.3 % ) “ high risk ” adenomas . Cancer was detected in four subjects . The faecal blood test yielded positive results in 0.8 % ( 0.2 % to 1.4 % ) but missed at least one cancer and 30 cases of adenoma which were found by sigmoidoscopy in the combined group . Use of histological criteria —shown elsewhere to correlate with future risk of colorectal cancer —to select “ positive ” patients could reduce recall for diagnostic colonoscopy from about 20 % to less than 5 % . Conclusions : Some of the predicted obstacles to screening with flexible sigmoidoscopy are surmountable . Clear evidence relating to efficacy will be obtained only from a r and omised controlled trial Background Three large r and omised trials have shown that screening for colorectal cancer ( CRC ) using the faecal occult blood test ( FOBt ) can reduce the mortality from this disease . The largest of these trials , conducted in Nottingham since 1981 , r and omised 152 850 individuals between the ages of 45 and 74 years to an intervention arm receiving biennial Haemoccult ( FOB ) test kit or to a control arm . In 2006 , the National Bowel Cancer Screening Programme was launched in Engl and using the FOBt , with the expectation that it will reduce CRC mortality . Aims To compare the CRC mortality and incidence in the intervention arm with the control arm after long-term follow-up . Methods The 152 850 r and omised individuals were followed up through local health records and central flagging ( Office for National Statistics ) . Results At a median follow-up of 19.5 years there was a 13 % reduction in CRC mortality ( 95 % CI 3 % to 22 % ) in the intervention arm despite an uptake at first invitation of approximately 57 % . The CRC mortality reduction in those accepting the first screening test , adjusted for the rate of non-compliers , was 18 % . There was no significant difference in mortality from causes other than CRC between the intervention and control arms . Despite removing 615 adenomas > 10 mm in size from the intervention arm , there was no significant difference in CRC incidence between the two arms . Conclusions Although the reduction in CRC mortality was sustained , further follow-up of the screened population has not shown a significant reduction in the CRC incidence . Moreover , despite the removal of many large adenomas there was no reduction in the incidence of invasive cancer which was independent of sex and site of the tumour BACKGROUND The efficacy of polypectomy in preventing colorectal cancer ( CRC ) has never been demonstrated in a controlled , prospect i ve study . This must be done by r and omization within a population with a high prevalence of colorectal polyps , and the feasibility and safety of endoscopic screening examination is a prerequisite for this type of study . METHODS The present study is a r and omized , controlled study of the feasibility and safety of flexible sigmoidoscopic screening of a normal population sample of 799 men and women aged 50 - 59 years , findings at 2 and 6 years ' colonoscopic follow-up , and the appearance of clinical colorectal cancer ( CRC ) after 10 years . RESULTS The attendance rate was high , and there were no complications . After 10 years 1 of 400 in the screening group had developed CRC ( in the group of 76 ( 19 % ) not attending for screening examination ) . Four of 399 controls developed CRC . CONCLUSIONS Poor yield of polyps at follow-up , slow growth of in situ polyps , and no clinical CRC among screenees after 10 years provides support to infrequent or no colonoscopic follow-up after initial polypectomy in individuals with otherwise average risk of CRC BACKGROUND & AIMS Despite poor performance , guaiac-based fecal occult blood tests ( G-FOBT ) are most frequently implemented for colorectal cancer screening . Immunochemical fecal occult blood tests ( I-FOBT ) are cl aim ed to perform better , without r and omized comparison in screening population s. Our aim was to r and omly compare G-FOBT with I-FOBT in a screening population . METHODS We conducted a population -based study on a r and om sample of 20,623 individuals 50 - 75 years of age , r and omized to either G-FOBT ( Hemoccult-II ) or I-FOBT ( OC-Sensor ) . Tests and invitations were sent together . For I-FOBT , the st and ard cutoff of 100 ng/ml was used . Positive FOBTs were verified with colonoscopy . Advanced adenomas were defined as > or=10 mm , high- grade dysplasia , or > or=20 % villous component . RESULTS There were 10,993 tests returned : 4836 ( 46.9 % ) G-FOBTs and 6157 ( 59.6 % ) I-FOBTs . The participation rate difference was 12.7 % ( P < .01 ) . Of G-FOBTs , 117 ( 2.4 % ) were positive versus 339 ( 5.5 % ) of I-FOBTs . The positivity rate difference was 3.1 % ( P < .01 ) . Cancer and advanced adenomas were found , respectively , in 11 and 48 of G-FOBTs and in 24 and 121 of I-FOBTs . Differences in positive predictive value for cancer and advanced adenomas and cancer were , respectively , 2.1 % ( P = .4 ) and -3.6 % ( P = .5 ) . Differences in specificities favor G-FOBT and were , respectively , 2.3 % ( P < .01 ) and -1.3 % ( P < .01 ) . Differences in intention-to-screen detection rates favor I-FOBT and were , respectively , 0.1 % ( P < .05 ) and 0.9 % ( P < .01 ) . CONCLUSIONS The number-to-scope to find 1 cancer was comparable between the tests . However , participation and detection rates for advanced adenomas and cancer were significantly higher for I-FOBT . G-FOBT significantly underestimates the prevalence of advanced adenomas and cancer in the screening population compared with I-FOBT BACKGROUND & AIMS We conducted a study to estimate population coverage and detection rate ( DR ) achievable through different strategies of colorectal cancer ( CRC ) screening . METHODS A population -based multicenter r and omized trial comparing 3 strategies was used : ( 1 ) biennial immunologic fecal occult blood test ( FIT ) , ( 2 ) " once only " sigmoidoscopy ( FS ) , and ( 3 ) " once only " colonoscopy ( TC ) . A r and om sample of men and women , aged 55 to 64 years , was drawn from general practitioners ' ( GP ) rosters . Eligible subjects , r and omized within GP , were mailed a personal invitation . Nonresponders in groups 2 and 3 were invited again at 12 and 24 months . Screenees with " high-risk " distal polyps ( villous component > 20 % , high- grade dysplasia , CRC , size > or=10 mm , > 2 adenomas ) at FS , or with positive FIT , were referred for TC . RESULTS The attendance rate was 32.3 % ( 1965/6075 ) for FIT , 32.3 % ( 1944/6018 ) for FS , 26.5 % ( 1597/6021 ) for TC . FIT detected 2 patients with CRC ( 0.1 % ) and 21 with an advanced adenoma ( 1.1 % ) . The corresponding figures were as follows : 12 ( 0.6 % ) and 86 ( 4.5 % ) patients , respectively , for FS ; 13 ( 0.8 % ) and 100 ( 6.3 % ) patients , respectively , for TC . To detect 1 advanced neoplasm , it would be necessary to invite 264 people with FIT , 60 with FS , 53 with TC . FS would have detected 27.3 % of the proximal advanced neoplasms detected at TC . Assuming the same participation rate at TC as at FS , 48 TCs would be necessary to detect 1 additional advanced neoplasm missed by FS . CONCLUSIONS When participants are offered 1 screening test , participation is lower in a TC than in an FS program . However , DR of advanced neoplasia is higher with TC OBJECTIVE The aim of this study is to compare the uptake of three mailed high-sensitivity fecal occult blood tests ( FOBTs ) . METHODS We conducted a parallel 3-arm r and omized controlled trial in an integrated healthcare delivery system in Washington State . From January 2010 through February 2011 , automated data were used to identify potentially eligible patients aged 50 - 74 due for colorectal cancer screening . Participants were mailed one of three FOBT kits ( 1- sample OC-Auto ® fecal immunochemical test [ FIT ] , 2- sample InSure ® FIT , or 3- sample guaiac Hemoccult SENSA ® ) , instructions , and a postage-paid return envelope . We performed a modified intent-to-treat analysis with return of any FOBT within 6 months of r and omization as the primary outcome . RESULTS Of the 9922 people invited , 2873 returned surveys , 2263 were r and omized , and 2234 were analyzed . FOBTs were returned by 1431 participants . At 6 months post-r and omization , the proportions screened by any FOBT were 0.69 ( 95 % confidence interval [ CI ] 0.66 - 0.72 ) for the OC-Auto arm , 0.64 ( 95 % CI : 0.61 - 0.68 ) for the InSure arm , and 0.61 ( 95 % CI : 0.58 - 0.65 ) for the Hemoccult SENSA arm ( P<0.001 for any difference ) . Pairwise comparisons showed significant differences between the OC-Auto group and each of the other groups after correction for multiple comparisons . CONCLUSION Uptake of mailed FOBT kits varies by kit type Abstract . Reduced mortality from colorectal cancer may be achieved by screening with faecal occult blood testing . Screening for neoplasia in the rectum and sigmoid colon with flexible sigmoidoscopy is suggested to be more effective , particular among persons between 50 and 60 years of age . A cohort of 6367 persons 55 – 56 years of age were r and omised to screening with rehydrated Hemoccult II tests ( HII group ) or with flexible videosigmoidoscopy directly ( FS group ) . In the HII group 59 % ( 1893/3183 ) attended , compared to 49 % ( 1353/3184 ) in the FS group . Of the 1893 persons who attended in the HII group , 4 % had a positive HII test and in 13 % ( 10/78 ) of them a neoplasm ≥1 cm in the rectum or sigmoid colon was diagnosed by endoscopy . The corresponding rate in the FS group was 2.3 % . Overall the number of persons with a neoplasm ≥1 cm diagnosed in the HII group was 10 and in the FS group 31 . A subgroup in the flexible sigmoidoscopy group , who also performed rehydrated HII tests , showed a sensitivity of the HII test for neoplasia ≥1 cm of 26 % and a specificity of 95.6 % . To find a neoplasm ≥1 cm in the rectum or sigmoid colon , 44 examinations were needed when using flexible sigmoidoscopy directly and 7 examinations when only those with positive HII tests were examined . In mass screening for neoplasia in the rectum and sigmoid colon , the relatively low prevalence of colorectal neoplasia at 55 – 56 years of age makes primary selection with rehydrated Hemoccult testing an alternative to the re source -consuming endoscopy of all invited persons . Résumé . Une baisse de la mortalité par cancer colo-rectal peut être obtenue à l'aide d'un dépistage visant à rechercher les pertes sanguines occultes . On estime que le dépistage des néoplasies du rectum et du sigmoïde à l'aide d'un sigmoïdoscope flexible semble être plus efficace chez les sujets âgés de 50 à 60 ans . Un collectife de 6367 personnes âgés de 55 à 56 ans ont été r and omisés afin de procéder à un dépistage soit par un test Hemoccult 2 réhydraté ( groupe HII ) soit à l'aide d'une vidéo-sigmoïdoscopie flexible ( groups FS ) . Dans le groupe HII , 59 % ( 1893/3183 ) ont subi le test comparativement à 49 % ( 1353/3184 ) dans le groupe FS . Des 1893 sujets qui ont été investigués dans le groupe HII , 4 % avaient un test HII positif et 1,3 % ( 10/78 ) étaient porteurs d'un néoplasme supérieur ou égal à 1 cm du rectum ou du sigmoïde . Le taux correspondant dans le groupe FS est de 2,3 % . Dix sujets dans le groupe HII et 31 dans le groupe FS sont porteurs d'une néoplasie > à 1 cm . Un sous-groupe de collectifs de sujets soumis à la sigmoïdoscopie a également subi un Hemoccult-test après réhydratation qui démontre une sensibilité du test HII pour des néoplasies > 1 cm dans 26 % des cas et une spécificitéà 95,6 % . La mise en évidence d'une néoplasie > 1 cm dans le rectum ou le sigmoïde exige que 44 sigmoïdoscopies flexibles soient réalisées directement et seulement 7 si le test à l'Hemoccult est positif . En case de dépistage de masse d'un cancer du rectum et du cólon sigmoïde , la prévalence relativement faible des cancers colo-rectaux à 55 – 56 ans fait que le dépistage à l'aide d'un Hemoccult réhydraté constitue une sélection primaire particulièrement utile comme alternative à une endoscopie onéreuse BACKGROUND Case-control studies and a voluntary-based follow-up study have suggested that repeated screening with faecal-occult-blood ( FOB ) tests can lead to a reduction in mortality from colorectal cancer ( CRC ) . The aim of this r and omised study was to compare mortality rates after FOB tests every 2 years during a 10-year period with those of unscreened similar controls . METHODS 140,000 people aged 45 - 75 years lived in Funen , Denmark , in August , 1985 , and were considered for inclusion in our study . Before r and omisation we excluded individuals who had CRC or precursor adenomas and those who had taken part in a previous pilot study . R and omisation of 137,485 people in blocks of 14 allocated three per 14 to the screening group ( 30,967 ) , three per 14 to the control group ( 30,966 ) , and eight not to be enrolled in the study ( 75,552 ) . Controls were not told about the study and continued to use health-care facilities as normal . Hemoccult-II blood tests ( with dietary restrictions but without rehydration ) were sent to screening-group participants . Only those participants who completed the first screening round were invited for further screening -- five rounds of screening during a 10-year period . Participants with positive tests were asked to attend to full examination and were offered colonoscopy whenever possible . The primary endpoint was death from CRC . FINDINGS Of the 30,967 screening-group participants , 20,672 ( 67 % ) completed the first screening round and were invited for further screening ; more than 90 % accepted repeated screenings . During the 10-year study , 481 people in the screening group had a diagnosis of CRC , compared with 483 unscreened controls . There were 205 deaths attributable to CRC in the screening group , compared with 249 deaths in controls . CRC mortality , including deaths attributable to complications from CRC treatment , was significantly lower in the screening group than in controls ( mortality ratio 0.82 [ 95 % CI 0.68 - 0.99 ] ) p = 0.03 ) . INTERPRETATION Our findings indicate that biennial screening by FOB tests can reduce CRC mortality . This study is being continued to improve its statistical power and to assess the effect of the removal of more precursor adenomas in the screening-group participants than in controls on CRC incidence BACKGROUND Most cases of colorectal cancer ( CRC ) develop from adenomas . Polypectomy is believed to reduce the incidence of CRC , but this effect has never been explored in prospect i ve controlled studies . The aim of the present study was to evaluate the effect of polypectomy on colorectal cancer incidence in a population -based screening program . METHODS In 1983 , 400 men and women aged 50 - 59 years were r and omly drawn from the population registry of Telemark , Norway . They were offered a flexible sigmoidoscopy and , if polyps were found , a full colonoscopy with polypectomy and follow-up colonoscopies in 1985 and 1989 . A control group of 399 individuals was drawn from the same registry . In 1996 both groups ( age , 63 - 72 years ) were invited to have a colonoscopic examination . Hospital files and the files of The Norwegian Cancer Registry were search ed to register any cases of CRC in the period 1983 - 96 . RESULTS At screening endoscopy 324 ( 81 % ) individuals attended in 1983 and 451 ( 71 % ) in 1996 . From 1983 to 1996 , altogether 10 individuals in the control group and 2 in the screening group were registered to have developed CRC ( relative risk , 0.2 ; 95 % confidence interval ( CI ) , 0.03 - 0.95 ; P = 0.02 ) . A higher overall mortality was observed in the screening group , with 55 ( 14 % ) deaths , compared with 35 ( 9 % ) in the control group ( relative risk , 1.57 ; 95 % CI , 1.03 - 2.4 ; P = 0.03 ) . CONCLUSION Endoscopic screening examination with polypectomy and follow-up was shown to reduce the incidence of CRC in a Norwegian normal population . The possible effect of screening on overall mortality should be addressed in larger studies Context Because the colonic mucosa constantly sheds cells , testing stool for cancer-related genes could be better for colorectal cancer screening than testing for occult bleeding , which is intermittent . Content A total of 3764 healthy adults had screening colonoscopy , fecal occult blood testing with Hemoccult and HemoccultSensa , and both a first- and a second-generation stool DNA test ( SDT-1 and SDT-2 , respectively ) for a battery of cancer genes . The sensitivity of SDT-1 and HemoccultSensa was very similar for screen-relevant neoplasms ( 20 % and 21 % , respectively ) , whereas the sensitivity of SDT-2 was 40 % . Caution The authors could not measure the specificity of SDT-2 . Implication A second-generation stool test for cancer genes is substantially more sensitive than fecal occult blood testing . The Editors Colorectal cancer remains the second most common cause of death among the types of cancer ( 1 ) . Although screening reduces colorectal cancer mortality ( 26 ) , observed reductions have been modest ( 6 , 7 ) and more than one half of adults in the United States have not received screening ( 8) . More accurate , user-friendly , and widely distributable tools have the potential to improve screening effectiveness , acceptability , and access . Several molecular approaches to screening stool for colorectal cancer have been studied and review ed ( 9 , 10 ) , and stool DNA testing has been jointly endorsed by the American Cancer Society , the U.S. Multi-Society Task Force on Colorectal Cancer , and the American College of Radiology ( 11 ) . The advantages of stool DNA testing include noninvasiveness , absence of bowel preparation or dietary restrictions , and ease of access via mail courier . However , the reported accuracy of stool DNA tests for the detection of colorectal neoplasia varies . In clinical studies that used different assays and selected groups ( 1220 ) , sensitivities ranged from 62 % to 100 % for colorectal cancer and 27 % to 82 % for advanced adenomas , with specificities ranging from 82 % to 100 % . In the only reported multicenter study on asymptomatic average-risk patients ( 21 ) , a precommercial multitarget DNA assay ( SDT-1 , a prototype of PreGenPlus , EXACT Sciences , Marlborough , Massachusetts ) detected 52 % of cases of colorectal cancer , compared with 13 % by Hemoccult ( P = 0.003 ) , at specificities of 94.4 % and 95.2 % , respectively . The accuracy of stool DNA testing is influenced by both biological and technical factors . A panel of markers must be used to accommo date the molecular heterogeneity of colorectal neoplasia , and marker selection critically affects discrimination ( 9 ) . Unlike occult bleeding , which is intermittent ( 22 ) , DNA markers seem to be shed continuously by exfoliation ( 23 ) . Thus , the multiple stool sampling practice d with fecal occult blood tests may not be necessary with stool DNA tests . However , recovery of the minute quantities of human DNA and assay of tumor-specific DNA alterations from stool present technical challenges and require exquisite laboratory sensitivity to achieve optimal detection rates . Our primary aim was to compare the precommercial stool DNA test ( SDT-1 ) , which was studied by Imperiale and colleagues ( 21 ) , with widely used fecal occult blood tests for the detection of screen-relevant neoplasia , defined as curable-stage colorectal cancer ( no distant metastases ) , high- grade dysplasia , or adenomas larger than 1 cm . A secondary aim was to explore neoplasm detection by another stool DNA test 2 ( SDT-2 ) , which uses a more broadly informative marker panel . Methods Table 1 lists the genes used in our test panels and defines several key terms . Table 1 . Definitions Design We conducted this multicenter , prospect i ve , triple-blinded trial , targeting average-risk persons , from 2001 to 2007 . A group of national experts on colorectal cancer screening advised on study design , and institutional review boards at each site approved the study . Because we did not know the effect of diet and medications on DNA assays , patients were r and omly assigned at entry to group A ( restriction of red meat and therapeutic doses of nonsteroidal anti-inflammatory drugs for 3 days before and during stool collection s ) or group B ( no such restrictions ) . All patients were asked not to ingest vitamin C for the 3 days before and during stool collection s. For the companion test , we chose Hemoccult ( Beckman Coulter , Fullerton , California ) , the most widely used fecal occult blood test , which was used in the trials that established the benefit of screening for fecal occult blood ( 24 ) . As a second companion test , we chose the next-generation guaiac test HemoccultSensa ( Beckman Coulter ) . We compared fecal blood results from 3 stools per patient with stool DNA on 1 stool . Experienced technicians performed stool DNA and occult blood testing in separate central laboratories without knowledge of clinical findings or the results of other tests . All patients who completed stool collection s also had colonoscopy , which served as the criterion st and ard . We did not have access to data until after they had been analyzed by statisticians and released by a data monitoring board . Participants We recruited asymptomatic persons age 50 to 80 years who were at average risk for colorectal cancer from communities surrounding 22 participating academic and regional health care systems through direct mail and multimedia advertisements . The exclusion criteria were structural colorectal evaluation ( endoscopic or radiographic ) within 10 years ; fecal blood testing within 1 year ; overt rectal bleeding within 1 month ; previous colorectal resection ; aerodigestive cancer within 5 years ; inability to stop therapeutic doses of nonsteroidal anti-inflammatory drugs or anticoagulants ; coagulopathy ; contraindications to colonoscopy ; chemotherapy within 3 months ; high-risk conditions for colorectal cancer , such as familial adenomatous polyposis , the Lynch syndrome , or other cancer syndromes ; previous colorectal cancer or adenoma ; inflammatory bowel disease ; or more than 2 first-degree relatives with colorectal neoplasia . Study assistants at each site registered participants and r and omly assigned them by using a Web-based management system ; distributed fecal blood test cards , stool collection containers , and colonoscopy preparation material s ; and provided instructions . Stool Collection and Processing Patients collected 3 stools by using plastic buckets mounted to the toilet seat . Promptly after each individual collection , patients smeared stool onto both windows of their Hemoccult and HemoccultSensa cards and then express-shipped smeared cards and the whole stool ( sealed in a bucket in an insulated container cooled with ice packs ) to the Mayo Clinic in Rochester , Minnesota . We froze the first stool from each participant whole at 80 C on receipt and sent it in batches on dry ice to EXACT Sciences ( Marlborough , Massachusetts ) for DNA assay ; each of the subsequent 2 stools were archived in aliquots at 80 C. If the first stool weighed less than 30 g or was received more than 48 hours after defecation , it was rejected for DNA analysis and the second or third stool ( if it met inclusion criteria ) was sent for DNA assay . Stool Assays DNA Testing All assays were polymerase chain reactionbased and were run at EXACT Sciences . Stool DNA test 1 was performed as described in Imperiale and colleagues ' study ( 21 ) . The marker panel for SDT-1 included 21 tumor-specific point mutations ( 3 on the K-ras gene , 10 on the APC gene , and 8 on the p53 gene ) ; the microsatellite-instability marker BAT-26 ; and long DNA , a marker for delayed apoptosis , which is characteristic of exfoliated neoplastic colonocytes ( 12 ) . For SDT-2 , sequence-specific DNA markers were detected by acrylamide gel electrophoresis , as described by Whitney and colleagues ( 24 ) ; the panel consisted of 3 tumor-specific markers broadly informative for both colorectal cancer and adenomas ( 25 ) : K-ras mutations , scanning of APC mutator cluster regions , and methylation of the vimentin gene . We used methods described elsewhere to detect mutant K-ras ( 12 ) , APC scanning ( 25 ) , and vimentin gene methylation ( 20 ) assays . We defined any positive component marker result according to the manufacturer 's preestablished criteria as a positive test result . Occult Blood Testing The manufacturer that developed the Hemoccult and HemoccultSensa cards , without rehydration , trained technicians on-site at the Mayo Clinic . As recommended by the manufacturer , the technicians added the catalyst solution to cards stored at ambient temperature within 48 to 72 hours of collection . We defined a spreading ( enlarging ) blue color in 60 seconds in any window of the cards as a positive result and any other result as negative . Colonoscopy After cathartic preparation , experienced endoscopists performed colonoscopy in all patients . If the examination did not reach the cecum or inspected less than 90 % of the mucosa , the patient was disqualified . Endophotographs documented cecal intubation , and the size and location of all lesions were recorded . Costs not covered by third parties were reimbursed by study funding . Pathologic Examination Local pathologists examined all endoscopically or surgically sample d lesions . A gastrointestinal pathologist at the coordinating site reexamined all lesions to confirm diagnosis . Classification discrepancies of screen-relevant neoplasms were adjudicated by a second expert pathologist . We categorized patients with multiple neoplasms according to the most advanced lesion . For assay of markers in screen-relevant neoplasms , DNA was extracted from microdissected tissue . Statistical Analysis We calculated sample size to ensure adequate power to detect differences in sensitivity comparisons . We powered the study to ensure an adequate number of cases of curable-stage colorectal cancer and high- grade dysplasia and assumed their combined prevalence to be at least 1.5 % . A sample size of 2900 would yield an expected 43 curable-stage cancer or high- grade dysplasia cases , Background : Two large true population studies in Europe have shown a significant reduction in mortality from colorectal cancer ( CRC ) by screening with a faecal occult blood test . In one trial conducted in Funen County , 61,933 individuals ( aged 45–75 years ) were r and omly allocated either to a control group or to receive a biennial Hemoccult‐II test . Methods : These individuals were followed from 1985 to 2002 and 9 screening rounds were performed . Results : First screening was accepted by 67 % ( 20,672 ) . Positivity rates varied between 0.8 % and 3.8 % , and the cumulative proportion of the test group having colonoscopy was 5.3 % . Screen‐detected CRC was early ( Dukes ' A ) in 36 % compared to 11 % among controls . Incidence of CRC was unchanged , but mortality was reduced by 11 % . This figure increased to 43 % in persons participating in all 9 rounds . No more than 8,558 were screened at the 9th round . Patients with CRC detected between screenings had better survival than controls . Death rates from causes other than CRC among participants never became higher than among controls . Conclusion : The lesser reduction in mortality from CRC of 11 % compared to 18 % after 5 screening rounds may be explained by the decrease in the number screened . Efficacy in those screened supports the introduction of countrywide screening in Denmark , but it must be ascertained that acceptability , proportion of early CRC and logistics all reach the same st and ard as in the r and omized trial IMPORTANCE Colorectal cancer is a major health burden . Screening is recommended in many countries . OBJECTIVE To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population -based trial . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 100,210 individuals aged 50 to 64 years , identified from the population of Oslo city and Telemark County , Norway . Screening was performed in 1999 - 2000 ( 55 - 64-year age group ) and in 2001 ( 50 - 54-year age group ) , with follow-up ending December 31 , 2011 . Of those selected , 1415 were excluded due to prior colorectal cancer , emigration , or death , and 3 could not be traced in the population registry . INTERVENTIONS Participants r and omized to the screening group were invited to undergo screening . Within the screening group , participants were r and omized 1:1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing ( FOBT ) . Participants with positive screening test results ( cancer , adenoma , polyp ≥10 mm , or positive FOBT ) were offered colonoscopy . The control group received no intervention . MAIN OUTCOMES AND MEASURES Colorectal cancer incidence and mortality . RESULTS A total of 98,792 participants were included in the intention-to-screen analyses , of whom 78,220 comprised the control group and 20,572 comprised the screening group ( 10,283 r and omized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT ) . Adherence with screening was 63 % . After a median of 10.9 years , 71 participants died of colorectal cancer in the screening group vs 330 in the control group ( 31.4 vs 43.1 deaths per 100,000 person-years ; absolute rate difference , 11.7 [ 95 % CI , 3.0 - 20.4 ] ; hazard ratio [ HR ] , 0.73 [ 95 % CI , 0.56 - 0.94 ] ) . Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group ( 112.6 vs 141.0 cases per 100,000 person-years ; absolute rate difference , 28.4 [ 95 % CI , 12.1 - 44.7 ] ; HR , 0.80 [ 95 % CI , 0.70 - 0.92 ] ) . Colorectal cancer incidence was reduced in both the 50- to 54-year age group ( HR , 0.68 ; 95 % CI , 0.49 - 0.94 ) and the 55- to 64-year age group ( HR , 0.83 ; 95 % CI , 0.71 - 0.96 ) . There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups . CONCLUSIONS AND RELEVANCE In Norway , once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening . Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00119912 Background : Screening for colorectal cancer ( CRC ) is widely accepted , but there is no consensus on the preferred strategy . We conducted a r and omised trial comparing participation and detection rates ( DR ) per screenee of guaiac-based faecal occult blood test ( gFOBT ) , immunochemical FOBT ( FIT ) , and flexible sigmoidoscopy ( FS ) for CRC screening . Methods : A representative sample of the Dutch population ( n = 15 011 ) , aged 50–74 years , was 1:1:1 r and omised prior to invitation to one of the three screening strategies . Colonoscopy was indicated for screenees with a positive gFOBT or FIT , and for those in whom FS revealed a polyp with a diameter ⩾10 mm ; adenoma with ⩾25 % villous component or high grade dysplasia ; serrated adenoma ; ⩾3 adenomas ; ⩾20 hyperplastic polyps ; or CRC . Results : The participation rate was 49.5 % ( 95 % confidence interval ( CI ) 48.1 to 50.9 % ) for gFOBT , 61.5 % ( CI , 60.1 to 62.9 % ) for FIT and 32.4 % ( CI , 31.1 to 33.7 % ) for FS screening . gFOBT was positive in 2.8 % , FIT in 4.8 % and FS in 10.2 % . The DR of advanced neoplasia was significantly higher in the FIT ( 2.4 % ; OR , 2.0 ; CI , 1.3 to 3.1 ) and the FS arm ( 8.0 % ; OR , 7.0 ; CI , 4.6 to 10.7 ) than the gFOBT arm ( 1.1 % ) . FS demonstrated a higher diagnostic yield of advanced neoplasia per 100 invitees ( 2.4 ; CI , 2.0 to 2.8 ) than gFOBT ( 0.6 ; CI , 0.4 to 0.8 ) or FIT ( 1.5 ; CI , 1.2 to 1.9 ) screening . Conclusion : This r and omised population -based CRC-screening trial demonstrated superior participation and detection rates for FIT compared to gFOBT screening . FIT screening should therefore be strongly preferred over gFOBT screening . FS screening demonstrated a higher diagnostic yield per 100 invitees than both FOBTs Objective Colorectal cancer screening by means of faecal immunochemical tests ( FITs ) requires successive screening rounds for an optimal preventive effect . However , data on the influence of the length of the screening interval on participation and diagnostic yield are lacking . Repeated FIT screening was therefore performed in a population -based trial comparing various repeat intervals . Design 7501 Dutch individuals aged 50–74 years were r and omly selected and invited for two 1- sample FIT screening rounds ( haemoglobin ( Hb ) concentration ≥50 ng/ml , corresponding to 10 μg Hb/g faeces ) with intervals of 1 ( group I ) , 2 ( group II ) or 3 years ( group III ) . Results In group I , participation was 64.7 % in the first screening round and 63.2 % in the second . The corresponding percentages for groups II and III were 61.0 % vs 62.5 % and 62.0 % vs 64.0 % . Triennial screening result ed in a higher participation rate in the second screening round compared with annual screening ( p=0.04 ) . The overall positivity rate in the second screening round was significantly lower compared with the first round ( 6.0 % vs 8.4 % ; OR 0.69 , 95 % CI 0.58 to 0.82 ) and did not depend on interval length ( p=0.23 ) . Similarly , the overall detection rate of advanced neoplasia was significantly lower in the second round compared with the first screening round ( 1.9 % vs 3.3 % ; OR 0.57 , 95 % CI 0.43 to 0.76 ) and also did not depend on interval length ( p=0.62 ) . The positive predictive value of the FIT did not significantly change over time ( 41 % vs 33 % ; p=0.07 ) . Conclusion The total number of advanced neoplasia found at repeat FIT screening is not influenced by the interval length within a range of 1–3 years . Furthermore , there is a stable and acceptably high participation in the second screening round . This implies that screening intervals can be tailored to local re sources |
2,169 | 27,196,645 | Peer support is a broad and robust strategy for reaching groups that health services too often fail to engage . | BACKGROUND Health disparities are aggravated when prevention and care initiatives fail to reach those they are intended to help .
Groups can be classified as hardly reached according to a variety of circumstances that fall into 3 domains : individual ( e.g. , psychological factors ) , demographic ( e.g. , socioeconomic status ) , and cultural-environmental ( e.g. , social network ) .
Several reports have indicated that peer support is an effective means of reaching hardly reached individuals .
However , no review has explored peer support effectiveness in relation to the circumstances associated with being hardly reached or across diverse health problems .
OBJECTIVES To conduct a systematic review assessing the reach and effectiveness of peer support among hardly reached individuals , as well as peer support strategies used . | Background Human re source limitations are a challenge to the delivery of antiretroviral therapy ( ART ) in low-re source setting s. We conducted a cluster r and omized trial to assess the effect of community-based peer health workers ( PHW ) on AIDS care of adults in Rakai , Ug and a. Methodology /Principal Findings 15 AIDS clinics were r and omized 2∶1 to receive the PHW intervention ( n = 10 ) or control ( n = 5 ) . PHW tasks included clinic and home-based provision of counseling , clinical , adherence to ART , and social support . Primary outcomes were adherence and cumulative risk of virologic failure ( > 400 copies/mL ) . Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART . Analysis was by intention to treat . From May 2006 to July 2008 , 1336 patients were followed . 444 ( 33 % ) of these patients were already on ART at the start of the study . No significant differences were found in lack of adherence ( < 95 % pill count adherence risk ratio [ RR ] 0.55 , 95 % confidence interval [ CI ] 0.23–1.35 ; < 100 % adherence RR 1.10 , 95 % CI 0.94–1.30 ) , cumulative risk of virologic failure ( RR 0.81 , 95 % CI 0.61–1.08 ) or in shorter-term virologic outcomes ( 24 week virologic failure RR 0.93 , 95 % CI 0.65–1.32 ; 48 week , RR 0.83 , 95 % CI 0.47–1.48 ; 72 week , RR 0.81 , 95 % CI 0.44–1.49 ) . However , virologic failure rates ≥96 weeks into ART were significantly decreased in the intervention arm compared to the control arm ( 96 week failure RR 0.50 , 95 % CI 0.31–0.81 ; 120 week , RR 0.59 , 95 % CI 0.22–1.60 ; 144 week , RR 0.39 , 95 % CI 0.16–0.95 ; 168 week , RR 0.30 , 95 % CI 0.097–0.92 ; 192 week , RR 0.067 , 95 % CI 0.0065–0.71 ) . Conclusions / Significance A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART , but did not affect cumulative risk of virologic failure , adherence measures , or shorter-term virologic outcomes . PHWs may be an effective intervention to sustain long-term ART in low-re source setting s. Trial Registration Clinical Trials.gov OBJECTIVES Marijuana was involved in 209,563 emergency department ( ED ) visits in 2006 , according to the Drug Abuse Warning Network . Although screening and brief intervention ( SBI ) has been effective in changing drinking among ED patients in a number of studies , tests of marijuana SBI in a pediatric emergency department ( PED ) have not yet been reported . The aim of this pilot study was to test whether SBI is effective in reducing marijuana consumption among youth and young adults presenting to a PED with a diverse range of clinical entities . METHODS A three-group r and omized controlled preliminary trial was structured to test 1 ) differences between Intervention ( Int ) and st and ard Assessed Control ( AC ) groups in marijuana consumption , from baseline to 12 months , and 2 ) the feasibility of adding a Nonassessed Control ( NAC ) group to evaluate regression to the mean and assessment reactivity . Patients aged 14 - 21 years in an urban , academic PED were screened during 2006 - 2007 , using st and ardized risk factor questions . Subjects were eligible if they used marijuana three or more times in the past 30 days , but were excluded for co-occurring high-risk alcohol use . Consented enrollees were r and omized to NAC , AC , and Int groups in a two-stage process that permitted blinding to status during assessment and follow-up . NACs received a re source h and out , written advice about marijuana use risks , and a 12-month follow-up appointment . ACs were assessed using st and ardized instruments and received re sources , written advice , and 3- and 12-month follow-up appointments . The Int group received assessment , re sources , written advice , 3- and 12-month appointments , a 20-minute structured conversation conducted by older peers , and a 10-day booster telephone call . A peer educator utilized a motivational style interview protocol adapted for adolescents to elicit daily life context and future goals , provide feedback , review pros and cons of marijuana use , assess readiness to change , evaluate strengths and assets , negotiate a contract for change , and make referrals to treatment and /or other re sources . Measurements included demographic information ; 30-day self-report of marijuana use ; attempts to quit , cut back , or change conditions of use ; and risk factor questions repeated at follow-up . RESULTS Among 7,804 PED patients screened , 325 were eligible ; 210 consented and enrolled ( Int , n = 68 ; AC , n = 71 ; NAC , n = 71 ) , with a 12-month follow-up rate of 71 % . For the primary objective , we compared Int to AC . At 12 months , Int participants were more likely to be abstinent for the past 30 days than ACs ( odds ratio [ OR ] for reported abstinence = 2.89 , 95 % confidence interval [ CI ] = 1.22 to 6.84 , p < 0.014 ) . The Int group had greater reduction in days used , baseline to 12 months , controlling for baseline ( Int = -7.1 vs. AC = -1.8 ) , were less likely to have been high among those who smoked ( OR = 0.39 , 95 % CI = 0.17 to 0.89 , p < 0.05 ) , and were more likely to receive referrals . In a linear regression model controlling for baseline use , NACs smoked 4 fewer days per month than ACs , but consumption was not significantly different , suggesting no assessment reactivity effect . CONCLUSIONS A preliminary trial of SBI promoted marijuana abstinence and reduced consumption among PED patients aged 14 - 21 years . A no-contact condition for the NAC group over the year after enrollment was insufficient to capture enrollees for follow-up across a range of baseline acuity Background Recent studies provide evidence for the effectiveness of Internet-based maintenance treatments for mental disorders . However , it is still unclear which participants might or might not profit from this particular kind of treatment delivery . Objective The study aim ed to identify moderators of treatment outcome in a transdiagnostic Internet-based maintenance treatment ( TIMT ) offered to patients after inpatient psychotherapy for mental disorders in routine care . Methods Using data from a r and omized controlled trial ( N=400 ) design ed to test the effectiveness of TIMT , we performed secondary analyses to identify factors moderating the effects of TIMT ( intervention ) when compared with those of a treatment-as-usual control condition . TIMT involved an online self-management module , asynchronous patient – therapist communication , a peer support group , and online-based progress monitoring . Participants in the control condition had unstructured access to outpatient psychotherapy , st and ardized outpatient face-to-face continuation treatment , and psychotropic management . Self-reports of psychopathological symptoms and potential moderators were assessed at the start of inpatient treatment ( T1 ) , at discharge from inpatient treatment/start of TIMT ( T2 ) , and at 3-month ( T3 ) and 12-month follow-up ( T4 ) . Results Education level , positive outcome expectations , and diagnoses significantly moderated intervention versus control differences regarding changes in outcomes between T2 and T3 . Only education level moderated change differences between T2 and T4 . The effectiveness of the intervention ( vs control ) was more pronounced among participants with a low ( vs high ) education level ( T2-T3 : B=–0.32 , SE 0.16 , P=.049 ; T2-T4 : B=–0.42 , SE 0.21 , P=.049 ) , participants with high ( vs low ) positive outcome expectations ( T2-T3 : B=–0.12 , SE 0.05 , P=.02 ) and participants with anxiety disorder ( vs mood disorder ) ( T2-T3 : B=–0.43 , SE 0.21 , P=.04 ) . Simple slope analyses revealed that despite some subgroups benefiting less from the intervention than others , all subgroups still benefited significantly . Conclusions This transdiagnostic Internet-based maintenance treatment might be suitable for a wide range of participants differing in various clinical , motivational , and demographic characteristics . The treatment is especially effective for participants with low education levels . These findings may generalize to other Internet-based maintenance treatments . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 28632626 ; http://www.controlled-trials.com/is rct n/pf/28632626 ( Archived by WebCite at http://www.webcitation.org/6IqZjTLrx ) Objective To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression . Design Multisite r and omised controlled trial . Setting Seven health regions across Ontario , Canada . Participants 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and r and omised with an internet based r and omisation service . Intervention Proactive individualised telephone based peer ( mother to mother ) support , initiated within 48 - 72 hours of r and omisation , provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session . Main outcome measures Edinburgh postnatal depression scale , structured clinical interview-depression , state-trait anxiety inventory , UCLA loneliness scale , and use of health services . Results After web based screening of 21 470 women , 701 ( 72 % ) eligible mothers were recruited . A blinded research nurse followed up more than 85 % by telephone , including 613 at 12 weeks and 600 at 24 weeks postpartum . At 12 weeks , 14 % ( 40/297 ) of women in the intervention group and 25 % ( 78/315 ) in the control group had an Edinburgh postnatal depression scale score > 12 ( χ2=12.5 , P<0.001 ; number need to treat 8.8 , 95 % confidence interval 5.9 to 19.6 ; relative risk reduction 0.46 , 95 % confidence interval 0.24 to 0.62 ) . There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services . For ethical reasons , participants identified with clinical depression at 12 weeks were referred for treatment , result ing in no differences between groups at 24 weeks . Of the 221 women in the intervention group who received and evaluated their experience of peer support , over 80 % were satisfied and would recommend this support to a friend . Conclusion Telephone based peer support can be effective in preventing postnatal depression among women at high risk . Trial registration IS RCT N 68337727 The increasing prevalence of diabetes and obesity , growing health disparities , and shortage of bilingual and culturally trained health care professionals underscore the role of trained community health workers ( CHWs ) to provide economically sustainable and culturally relevant services . This prospect i ve r and omized design evaluated the relative effectiveness of a CHW intervention among Hispanic persons with newly diagnosed type 2 diabetes , as compared with usual clinic practice in three inner-city health centers . In sum , 189 Hispanic patients newly diagnosed with type 2 diabetes were r and omly assigned to one of three 6-month diabetes management approaches — CHW , case management , and st and ard provider care— and assessed for diabetes-related health measures and clinical indicators at baseline and postintervention . Participants in the CHW group achieved greater improvements than did the controls in program measures : health status , emergency department utilization , dietary habits , physical activity , and medication adherence . They also had 2.9 times greater odds of decreasing body mass index OBJECTIVE Demonstrate the effective use of community-based evidence for health promotion by Lady Health Workers ( LHWs ) in Sindh , Pakistan . METHODS A baseline study on mothers and children provided local evidence for risk communication tools design ed and tested by LHWs . The communities were r and omized to intervention and control . LHWs visited women before and after childbirth to discuss safe practice s in pregnancy , in the intervention group LHW using the new tools and in the control group using their st and ard procedures . A household survey and focus groups permitted assessment of the impact of the intervention . RESULTS Women in the intervention communities were more likely to attend prenatal checkups , to stop routine heavy work during pregnancy , to give colostrum to newborn babies , and to maintain exclusive breastfeeding for four months . Community focus groups confirmed a positive reaction to the tools . CONCLUSION Discussion by lay health workers of local evidence underlying safe motherhood messages improved uptake of protective health practice s. PRACTICE IMPLICATION S Door-to-door health promotion based on culturally appropriate interaction around relevant evidence can have a positive impact on health practice s. Engaging health workers from the onset builds capacities , improves dialogue within the health system and performance of frontline health workers ABSTRACT BACKGROUND Peer health coaching is an effective method of enhancing self-management support in patients with diabetes . It is unclear whether peer health coaching is equally beneficial to all patients with poor glycemic control , or is most effective for subgroups of patients . OBJECTIVE To examine whether the effect of peer health coaching on hemoglobin A1c ( A1c ) is modified by characteristics that are known to be associated with diabetes control . DESIGN Sub-group analyses of r and omized control trial . PARTICIPANTS Two hundred and ninety nine patients with diabetes receiving care in public health clinics who participated in a r and omized controlled trial of peer health coaches . MAIN MEASURES We examined whether the association between study group and change in A1c was modified by differences in patients ’ demographic , behavioral or psychosocial characteristics . Analyses were adjusted for co-variables associated with change in A1c . KEY RESULTS The effect of coaching on patient A1c was modified by patients ’ level of self-management and degree of medication adherence as baseline ( p = .02 , and p = .03 respectively in adjusted models ) . For participants with “ low ” self-management ( one st and ard deviation below the mean score ) , the usual care group experienced a slight increase in A1c ( 0.3 % ) , while the health coaching group experienced a decrease ( −0.9 % ) . For participants with “ high ” self-management ( one st and ard deviation above the mean score ) , both groups experienced a similar decrease in A1c ( usual care group : -1.0 % ; health coaching group : −1.1 % ) . Participants with “ low ” medication adherence in the usual care group experienced an increase in A1c ( 0.5 % ) , while the health coaching group experienced a decrease ( −0.8 % ) . Participants with “ high ” medication adherence experienced similar decreases ( usual care group : −1.1 % ; health coaching group : −1.3 % ) . CONCLUSION Peer health coaching had a larger effect on lowering A1c in patients with low levels of medication adherence and self-management support than in patients with higher levels . Peer health coaching interventions may be most effective if targeted to high-risk patients with diabetes with poor glycemic control and with poor self-management and medication adherence Objective : To evaluate the effect of peer support ( mother-to-mother ) on depressive symptomatology among mothers identified as high-risk for postpartum depression ( PPD ) . Method : Forty-two mothers in British Columbia were identified as high-risk for PPD according to the Edinburgh Postnatal Depression Scale ( EPDS ) and r and omly assigned to either a control group ( that is , to st and ard community postpartum care ) or an experimental group . The experimental group received st and ard care plus telephone-based peer support , initiated within 48 to 72 hours of r and omization , from a mother who previously experienced PPD and attended a 4-hour training session . Research assistants blind to group allocation conducted follow-up assessment s on diverse outcomes , including depressive symptomatology , at 4 and 8 weeks postr and omization . Results : Significant group differences were found in probable major depressive symptomatology ( EPDS > 12 ) at the 4-week ( χ2 = 5.18 , df = 1 ; P = 0.02 ) and 8-week ( χ2 = 6.37 , df = 1 ; P = 0.01 ) assessment s. Specifically , at the 4-week assessment 40.9 % ( n = 9 ) of mothers in the control group scored > 12 on the EPDS , compared with only 10 % ( n = 2 ) in the experimental group . Similar findings were found at the 8-week assessment , when 52.4 % ( n = 11 ) of mothers in the control group scored > 12 on the EPDS , compared with 15 % ( n = 3 ) of mothers in the experimental group . Of the 16 mothers in the experimental group who evaluated the intervention , 87.5 % were satisfied with their peer-support experience . Conclusions : Telephone-based peer support may effectively decrease depressive symptomatology among new mothers . The high maternal satisfaction with , and acceptance of , the intervention suggests that a larger trial is feasible BACKGROUND Breastfeeding peer counseling has improved breastfeeding rates in developing countries ; however , its impact in this country has not been adequately evaluated . OBJECTIVE To evaluate the effectiveness of an existing , breastfeeding peer counseling program within the United States . DESIGN R and omized , prospect i ve , controlled trial in which participants were recruited prenatally and r and omly assigned to receive either routine breastfeeding education or routine breastfeeding education plus peer counseling . SETTING An urban hospital serving a large population of low-income Latinas . PARTICIPANTS Pregnant women ( < or = 26 weeks ' gestation ) were recruited from the hospital 's prenatal clinic . Inclusion criteria specified that participants be low income , be considering breastfeeding , have delivered a healthy , full-term singleton , and have access to a telephone . Intervention Breastfeeding peer counseling services included 1 prenatal home visit , daily perinatal visits , 3 postpartum home visits , and telephone contact as needed . MAIN OUTCOME MEASURES Breastfeeding rates at birth and 1 , 3 , and 6 months postpartum . RESULTS The proportion not initiating breastfeeding was significantly lower in the intervention group than among controls ( 8/90 [ 9 % ] vs 17/75 [ 23 % ] ; relative risk , 0.39 ; 95 % confidence interval , 0.18 - 0.86 ) . The probability of stopping breastfeeding also tended to be lower in the intervention group at both 1 month ( 36 % vs 49 % ; relative risk , 0.72 ; 95 % confidence interval , 0.50 - 1.05 ) and 3 months ( 56 % vs 71 % ; relative risk , 0.78 ; 95 % confidence interval , 0.61 - 1.00 ) . CONCLUSION These findings demonstrate that , in the United States , peer counselors can significantly improve breastfeeding initiation rates and have an impact on breastfeeding rates at 1 and 3 months post partum BACKGROUND Few studies compare the influence of different types of dietary interventions on the dietary practice s of Latinas in the short and long term . The present study examined the 1-year impact of two innovative behavior-change approaches to reduce dietary fat and increase fiber . DESIGN Three-group r and omized controlled trial : ( 1 ) personalized dietary counseling via lay heath advisors ( promotoras ) plus tailored print material s delivered via the mail , ( 2 ) tailored mailed print material s only , and ( 3 ) targeted mailed " off-the-shelf " material s. SETTING / PARTICIPANTS A total of 357 Latinas were r and omly assigned to the three aforementioned conditions . INTERVENTION Promotora and tailored print material s. MAIN OUTCOME MEASURES Fat intake ( total grams of fat and percent calories from dietary fat ) and number of grams of dietary fiber . RESULTS Earlier work reported that at immediate post-intervention the promotora group achieved significantly lower levels of total fat grams , and lower levels of energy intake , total saturated fat , total carbohydrates , glucose , and fructose than the targeted group . However , the present longitudinal analyses suggest that the effects achieved by the promotoras dissipated over the 12-month follow-up period while the effects of the tailored group concurrently improved . CONCLUSIONS The high interactivity ( i.e. , calls , visits ) of the promotora condition may have been the most salient reinforcer and may have led to further tailoring , making this type of intervention more effective than the comparison groups in the short term . Further research should explore whether booster sessions involving promotoras help to maintain the impact over time OBJECTIVES We assessed the effectiveness of a community health worker intervention focused on reducing exposure to indoor asthma triggers . METHODS We conducted a r and omized controlled trial with 1-year follow-up among 274 low-income households containing a child aged 4 - 12 years who had asthma . Community health workers provided in-home environmental assessment s , education , support for behavior change , and re sources . Participants were assigned to either a high-intensity group receiving 7 visits and a full set of re sources or a low-intensity group receiving a single visit and limited re sources . RESULTS The high-intensity group improved significantly more than the low-intensity group in its pediatric asthma caregiver quality -of-life score ( P=.005 ) and asthma-related urgent health services use ( P=.026 ) . Asthma symptom days declined more in the high-intensity group , although the across-group difference did not reach statistical significance ( P=.138 ) . Participant actions to reduce triggers generally increased in the high-intensity group . The projected 4-year net savings per participant among the high-intensity group relative to the low-intensity group were 189 - 721 dollars . CONCLUSIONS Community health workers reduced asthma symptom days and urgent health services use while improving caregiver quality -of-life score . Improvement was greater with a higher-intensity intervention OBJECTIVE To test whether community health workers are able to reach low-income parents of African American children hospitalized for asthma and to reduce rehospitalization among them . DESIGN A r and omized controlled evaluation of usual care vs 2-year asthma coach intervention . SETTING An urban children 's hospital and the surrounding community . PARTICIPANTS A population -based sample of 306 children hospitalized for asthma met the inclusion criteria of being 2 to 8 years of age , of African American ethnicity , and having Medicaid coverage . Of these , 200 were contacted and 191 recruited with commitment to evaluation activities but , in order to assess reach , no commitment to participating in intervention . INTERVENTIONS Coaches reinforced basic asthma education and encouraged key management behaviors through home visits and phone calls tailored to parent 's readiness to adopt management practice s and emphasizing a nondirective supportive style ( cooperative and accepting of feelings and choices ) . OUTCOME MEASURES The reach of intervention to parents , contacts with coaches , and rehospitalization over 2 years based on hospital records . RESULTS Within 3 months of r and omization to the asthma coach group , 89.6 % of parents had at least 1 substantive contact with the coach , with an average of 21.1 contacts per parent over the 24-month intervention . The proportion of children rehospitalized was 35 of 96 ( 36.5 % ) in the asthma coach group and 55 of 93 ( 59.1 % ) in the usual care group ( P < .01 ) , controlling for parental education and child age , sex , and hospitalization in the year prior to the index hospitalization . In surveys , parents indicated the importance of the nondirective approach to support . CONCLUSIONS An asthma coach can reach low-income parents of African American children hospitalized for asthma and reduce rehospitalization among the children Pediatric asthma is a growing public health issue , disproportionately affecting low-income people and people of color . Exposure to indoor asthma triggers plays an important role in the development and exacerbation of asthma . We describe the implementation of the Seattle-King County Healthy Homes Project , a r and omized , controlled trial of an outreach/education intervention to improve asthma-related health status by reducing exposure to allergens and irritants in the home . We r and omly assigned 274 low-income children with asthma ages 4 - 12 to either a high- or a low-intensity group . In the high-intensity group , community health workers called Community Home Environmental Specialists ( CHES ) conducted initial home environmental assessment s , provided individualized action plans , and made additional visits over a 12-month period to provide education and social support , encouragement of participant actions , provision of material s to reduce exposures ( including bedding encasements ) , assistance with roach and rodent eradication , and advocacy for improved housing conditions . Members of the low-intensity group received the initial assessment , home action plan , limited education during the assessment visit , and bedding encasements . We describe the recruitment and training of CHES and challenges they faced and explain the assessment and exposure reduction protocol s addressing dust mites , mold , tobacco smoke , pets , cockroaches , rodents , dust , moisture , and toxic or hazardous chemicals . We also discuss the gap between the practice s recommended in the literature and what is feasible in the home . We accomplished home interventions and participants found the project very useful . The project was limited in resolving structural housing quality issues that contributed to exposure to indoor triggers OBJECTIVE To compare the marginal benefit of in-home asthma self-management support provided by community health workers ( CHWs ) with st and ard asthma education from clinic-based nurses . DESIGN R and omized controlled trial . SETTING Community and public health clinics and homes . PARTICIPANTS Three hundred nine children aged 3 to 13 years with asthma living in low-income households . INTERVENTIONS All participants received nurse-provided asthma education and referrals to community re sources . Some participants also received CHW-provided home environmental assessment s , asthma education , social support , and asthma-control re sources . OUTCOME MEASURES Asthma symptom-free days , Pediatric Asthma Caretaker Quality of Life Scale score , and use of urgent health services . RESULTS Both groups showed significant increases in caretaker quality of life ( nurse-only group : 0.4 points ; 95 % confidence interval [ CI ] , 0.3 - 0.6 ; nurse + CHW group : 0.6 points ; 95 % CI , 0.4 - 0.8 ) and number of symptom-free days ( nurse only : 1.3 days ; 95 % CI , 0.5 - 2.1 ; nurse + CHW : 1.9 days ; 95 % CI , 1.1 - 2.8 ) , and absolute decreases in the proportion of children who used urgent health services in the prior 3 months ( nurse only : 17.6 % ; 95 % CI , 8.1%-27.2 % ; nurse + CHW : 23.1 % ; 95 % CI , 13.6%-32.6 % ) . Quality of life improved by 0.22 more points in the nurse + CHW group ( 95 % CI , 0.00 - 0.44 ; P = .049 ) . The number of symptom-free days increased by 0.94 days per 2 weeks ( 95 % CI , 0.02 - 1.86 ; P = .046 ) , or 24.4 days per year , in the nurse + CHW group . While use of urgent health services decreased more in the nurse + CHW group , the difference between groups was not significant . CONCLUSION The addition of CHW home visits to clinic-based asthma education yielded a clinical ly important increase in symptom-free days and a modest improvement in caretaker quality of life Participants ( N=357 ) were r and omly assigned to 1 of 3 conditions : lay health advisor ( promotora ) plus tailored print material s , tailored print material s only ( tailored ) , or off-the-shelf print material s ( control ) . The primary outcomes were calories from fat and daily grams of fiber . Secondary outcomes included total energy intake , total and saturated fat intake , and total carbohydrates . Adjusted for baseline values , calories from fat were 29 % , 30 % , and 30 % for the promotora , tailored , and control conditions , respectively , and grams of fiber consumed were 16 g , 17 g , and 16 g. Significant Condition X Time interactions were not observed between baseline and 12-weeks postintervention . The LHA condition achieved significantly lower levels of energy intake , total fat and saturated fat , and total carbohydrates . The relative superiority of the promotora condition may derive from the personal touch achieved in the face-to-face interactions or from the women 's use of print material s under the promotora 's guidance OBJECTIVE To determine the efficacy of a peer-led social support intervention involving support groups and telephone contacts compared with st and ard clinical care to enhance antiretroviral medication adherence . DESIGN R and omized controlled trial with follow-up . Participants were 136 HIV-positive indigent mainly African American and Puerto Rican men and women recruited from an outpatient clinic in the Bronx , New York . The 3-month intervention was delivered by other HIV-positive clinic patients trained in addressing barriers to adherence and sensitively providing appraisal , spiritual , emotional , and informational adherence-related social support . MAIN OUTCOME MEASURES Medical chart- abstract ed HIV-1 RNA viral load , antiretroviral adherence according to electronic drug monitoring and participant self-report , and social support and depressive symptomatology . All assessment s conducted at baseline , 3 months , and 6 months . RESULTS Intent-to-treat and as-treated analyses indicated no between-conditions intervention effects on the primary outcome of HIV-1 RNA viral load or any of the secondary outcomes at immediate postintervention or follow-up . Post hoc analyses within the intervention condition indicated greater intervention exposure was associated with higher self-reported adherence , higher social support , and lower depressive symptomatology at follow-up , even after controlling for baseline adherence . CONCLUSION Null findings , consistent with the limited literature on efficacious highly active antiretroviral therapy ( HAART ) adherence interventions , may be due to insufficient exposure to the intervention , its low intensity , or the nature of the sample -a heterogeneous HAART-experienced group of patients with high levels of substance use and multiple other competing stressors . Overall , findings highlight the need for more comprehensive and intensive efforts to battle nonadherence Despite the prevalence of Internet support groups for individuals with mental illnesses little is known about the potential benefits , or harm , of participating in such groups . Therefore , this r and omized controlled trial sought to determine the impact of unmoderated , unstructured Internet peer support , similar to what is naturally occurring on the Internet , on the well-being of individuals with psychiatric disabilities . Three hundred individuals resident in the USA diagnosed with a Schizophrenia Spectrum or an Affective Disorder were r and omized into one of three conditions : experimental Internet peer support via a listserv , experimental Internet peer support via a bulletin board , or a control condition . Three measurement time points , baseline , 4- and 12 months post-baseline , assessed well-being by examining measures of recovery , quality of life , empowerment , social support , and distress . Time × group interactions in the repeated measures ANOVA showed no differences between conditions on the main outcomes . Post-hoc repeated measures ANOVAs found that those individuals who participated more in Internet peer support reported higher levels of distress than those with less or no participation ( p = 0.03 ) . Those who reported more positive experiences with the Internet peer support group also reported higher levels of psychological distress than those reporting less positive experiences ( p = 0.01 ) . Study results therefore do not support the hypothesis that participation in an unmoderated , unstructured Internet listserv or bulletin board peer support group for individuals with psychiatric disabilities enhances well-being . Counterintuitive findings demonstrating those who report more positive experiences also experienced higher levels of distress are discussed but we also point to the need for additional research . Future research should explore the various structures , formats , and interventions of Internet support , as well as the content and quality of interactions . Knowledge generated from such research can help to inform policies and guidelines for safely navigating online re sources and supports to gain maximum benefit This study examined the impact of a tailored nutrition intervention at 3 and 6 months postintervention . In all , 357 Latinas were r and omly assigned to one of three conditions : ( 1 ) a control condition comprised of previously developed Spanish language targeted material s , ( 2 ) tailored print material s , or ( 3 ) tailored print material s accompanied by personalized dietary counseling via lay heath advisors ( promotoras ) . At 6 months postintervention , significant group by time interactions were observed on the dietary behavioral strategies scales . The promotora condition result ed in significant behavior change initially ; however , receipt of tailored and control material s was instrumental in continued behavior change after intervention activities had ceased . Group main effects suggested that the promotora condition was superior at reducing barriers and improving family interactions supporting healthy behaviors . The promotora model is an effective method for changing important dietary behaviors and psychosocial determinants , but longer term behavior change is achievable with less expensive intervention methods BACKGROUND Neonatal mortality accounts for a high proportion of deaths in children under the age of 5 years in Bangladesh . Therefore the project for advancing the health of newborns and mothers ( Projahnmo ) implemented a community-based intervention package through government and non-government organisation infrastructures to reduce neonatal mortality . METHODS In Sylhet district , 24 clusters ( with a population of about 20 000 each ) were r and omly assigned in equal numbers to one of two intervention arms or to the comparison arm . Because of the study design , masking was not feasible . All married women of reproductive age ( 15 - 49 years ) were eligible to participate . In the home-care arm , female community health workers ( one per 4000 population ) identified pregnant women , made two antenatal home visits to promote birth and newborn-care preparedness , made postnatal home visits to assess newborns on the first , third , and seventh days of birth , and referred or treated sick neonates . In the community-care arm , birth and newborn-care preparedness and careseeking from qualified providers were promoted solely through group sessions held by female and male community mobilisers . The primary outcome was reduction in neonatal mortality . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number 00198705 . FINDINGS The number of clusters per arm was eight . The number of participants was 36059 , 40159 , and 37598 in the home-care , community-care , and comparison arms , respectively , with 14 769 , 16 325 , and 15 350 livebirths , respectively . In the last 6 months of the 30-month intervention , neonatal mortality rates were 29.2 per 1000 , 45.2 per 1000 , and 43.5 per 1000 in the home-care , community-care , and comparison arms , respectively . Neonatal mortality was reduced in the home-care arm by 34 % ( adjusted relative risk 0.66 ; 95 % CI 0.47 - 0.93 ) during the last 6 months versus that in the comparison arm . No mortality reduction was noted in the community-care arm ( 0.95 ; 0.69 - 1.31 ) . INTERPRETATION A home-care strategy to promote an integrated package of preventive and curative newborn care is effective in reducing neonatal mortality in communities with a weak health system , low health-care use , and high neonatal mortality AIMS To study the effectiveness of a peer-led self-management coaching intervention in recently diagnosed patients with Type 2 diabetes . METHODS R and omized controlled trial of recently diagnosed patients with Type 2 diabetes from 54 participating general practice s. The intervention group received three home visits by an experienced peer ( expert patient ) who adhered to the recommended treatment and lifestyle guidelines . Together with their expert patient , participants set feasible goals and these were evaluated in the next visit . Participants in the control group received care as usual . At baseline , 3 months and 6 months post-intervention , participants completed a question naire measuring changes in self-efficacy , coping , physical activity , dietary habits , psychological well-being , depressive symptoms and diabetes related distress . RESULTS In total , 327 patients were eligible for inclusion in the study of which 133 consented to participate . In participating patients , self-efficacy , coping and saturated fat intake improved significantly over time . Analyses of participants with low self-efficacy at baseline ( 25th percentile : 44 ) revealed a significant time × group difference , F = 3.71 ; P = 0.03 . Participants who reported low psychological well-being at baseline increased substantially throughout the study ( F = 23.84 ; P < 0.01 ) but no significant time × group differences were found . CONCLUSIONS A peer-led self-management coaching programme for recently diagnosed patients with Type 2 diabetes improved self-efficacy of patients experiencing low self-efficacy shortly after diagnosis Objective In a r and omized trial , a guided diabetes peer support intervention improved glycemic control ( A1c ) , with a difference in A1c change between groups of 0.58 % ( p = 0.004 ) . The current study examined whether improvements in insulin uptake and perceived diabetes social support mediated the intervention ’s impact on A1c . We also examined potential moderation by patients ’ health literacy , diabetes social support , or diabetes distress . Methods We conducted secondary analyses for 212 type 2 diabetes patients participating in the trial using accepted methods for testing mediation and moderation effects . Results : Roughly half ( 49 % , 95 % CI : 3–80 % ) of the A1c effect was mediated by increased insulin use , while changes in diabetes social support had a negligible impact . A1c impacts varied across subgroups defined by baseline diabetes social support and functional health literacy ( both p < 0.01 ) . The intervention was particularly beneficial among patients with low baseline diabetes support or literacy levels . The intervention had a greater impact on A1c among patients with more frequent engagement in peer support calls ( p < 0.01 ) . Discussion Patients receiving increased peer support had improved glycemic control largely due to their greater likelihood of initiating insulin . Greater intervention engagement was associated with stronger effects . The intervention had its greatest benefits among patients with low support or poorer health literacy |
2,170 | 29,718,436 | Results and conclusions Travellers ' diarrhoea and use of pre/probiotics : There is no significant evidence to suggest the benefit of using pre or probiotics to prevent or treat TD .
A new second generation of B-GOS prebiotics shows some potential in preventing the incidence and symptoms of TD but lack high levels of grade d evidence .
The evidence behind water purification and diarrhoeal disease : Evidence suggests there is no direct correlation that water purification has an impact on diarrhoeal disease , although some studies underline the value of water purification .
With new water purification products and methods being introduced a benefit could be found for publishing effectiveness against pathogen groups to improve comparison .
Are travellers given good sanitary advice and do they follow it ?
Within the clinical sector the advice provided and the outcomes of advice provision do not correlate with a reduction in TD as a variance can occur by travellers ' changes and behaviours towards the advice given .
Following recommended advice and consuming higher risks foods do not correspond directly with levels of reported TD , suggesting attitudes and practice s deviate away from this advice when travelling | Background This is a review of some of the non-pharmacotherapeutic interventions in travellers diarrhoea ( TD ) looking particularly at the role of pre and probiotics , the evidence behind water purification and the impact of advice given and its adherence by travellers .
The use of bottled water is question ed as being unreliable due to the inconsistencies of microbiological safety . | Background Travellers are at risk of acquiring infectious diseases during travel , with risks differing by destination , travel and traveller characteristics . A pre-travel health consultation may minimize this risk . However , uptake of pre-travel health advice remains low . We investigated pre-travel health preparations and disease-specific risk behaviours among notified cases of selected travel-associated infectious diseases imported into Australia . Methods Prospect i ve enhanced surveillance of notified cases of typhoid , paratyphoid , measles , hepatitis A , hepatitis E , malaria and chikungunya was conducted in two Australian states between February 2013 and January 2014 . Details of pre-travel health preparation and disease-specific risk behaviours were collected . Results Among 180 cases associated with international travel , 28 % were < 18 years , 65 % were VFR travellers and 22 % were frequent travellers , having travelled ≥5 times in the past 5 years . 25 % had sought pre-travel advice from a healthcare provider , and 16 % reported a pre-travel vaccine . Seeking pre-travel health advice did not differ by immigrant status ( P = 0.22 ) or by reason for travel ( P = 0.13 ) but was more commonly sought by first time travellers ( P = 0.03 ) . Travellers visiting friends and relatives were more likely to report at-risk activities of brushing teeth with tap water ( P < 0.001 ) and eating uncooked food ( P = 0.03 ) during travel compared to other travellers . Conclusions Pre-travel health advice seeking practice s and vaccine uptake was suboptimal among cases of notified disease . The results of this study highlight the need for a better underst and ing of barriers to pre-travel health seeking , particularly among high risk travellers , to reduce the importation of infectious diseases into Australia Prebiotics are nondigestible food ingredients that encourage proliferation of selected groups of the colonic microflora , thereby altering the composition toward a more beneficial community . In the present study , the prebiotic potential of a novel galactooligosaccharide ( GOS ) mixture , produced by the activity of galactosyltransferases from Bifidobacterium bifidum 41171 on lactose , was assessed in vitro and in a parallel continuous r and omized pig trial . In situ fluorescent hybridization with 16S rRNA-targeted probes was used to investigate changes in total bacteria , bifidobacteria , lactobacilli , bacteroides , and Clostridium histolyticum group in response to supplementing the novel GOS mixture . In a 3-stage continuous culture system , the bifidobacterial numbers for the first 2 vessels , which represented the proximal and traverse colon , increased ( P < 0.05 ) after the addition of the oligosaccharide mixture . In addition , the oligosaccharide mixture strongly inhibited the attachment of enterohepatic Escherichia coli ( P < 0.01 ) and Salmonella enterica serotype Typhimurium ( P < 0.01 ) to HT29 cells . Addition of the novel mixture at 4 % ( wt : wt ) to a commercial diet increased the density of bifidobacteria ( P < 0.001 ) and the acetate concentration ( P < 0.001 ) , and decreased the pH ( P < 0.001 ) compared with the control diet and the control diet supplemented with inulin , suggesting a great prebiotic potential for the novel oligosaccharide mixture Daniel Maeusezahl and colleagues conducted a cluster-r and omized controlled trial in rural Bolivia of solar drinking water disinfection , and find only moderate compliance with the intervention and no evidence of reduction in diarrhea among children Background / Objectives : Prebiotics have attracted interest for their ability to positively affect the colonic microbiota composition , thus increasing resistance to infection and diarrhoeal disease . This study assessed the effectiveness of a prebiotic galacto-oligosaccharide mixture ( B-GOS ) on the severity and /or incidence of travellers ' diarrhoea ( TD ) in healthy subjects . Subjects/ Methods : The study was a placebo-controlled , r and omized , double blind of parallel design in 159 healthy volunteers , who travelled for minimum of 2 weeks to a country of low or high risk for TD . The investigational product was the B-GOS and the placebo was maltodextrin . Volunteers were r and omized into groups with an equal probability of receiving either the prebiotic or placebo . The protocol comprised of a 1 week pre-holiday period recording bowel habit , while receiving intervention and the holiday period . Bowel habit included the number of bowel movements and average consistency of the stools as well as occurrence of abdominal discomfort , flatulence , bloating or vomiting . A clinical report was completed in the case of diarrhoeal incidence . A post- study question naire was also completed by all subjects on their return . Results : Results showed significant differences between the B-GOS and the placebo group in the incidence ( P<0.05 ) and duration ( P<0.05 ) of TD . Similar findings occurred on abdominal pain ( P<0.05 ) and the overall quality of life assessment ( P<0.05 ) . Conclusions : Consumption of the tested galacto-oligosaccharide mixture showed significant potential in preventing the incidence and symptoms of TD BACKGROUND Travelers ' diarrhea ( TD ) is a significant problem for travelers . TD is treatable once it occurs , but few options for prevention exist . Probiotics have been studied for prevention or treatment of TD ; however , very few combination probiotics have been studied . Therefore , the purpose of this study was to determine if prophylactic use of an oral synbiotic could reduce the risk of acquiring TD and reduce antibiotic use if TD occurred . METHODS Healthy subjects traveling to an area of the world with an increased risk of TD were eligible . All subjects received pre-travel counseling and were provided antibiotics and antidiarrheals ( loperamide ) for use only if TD developed . The subjects were blinded and r and omized to take two capsules of placebo or oral synbiotic ( a combination of two probiotics and a prebiotic ) called Agri-King Synbiotic ( AKSB ) beginning 3 days prior to departure , daily while traveling , and for 7 days after return . All subjects kept symptom and medication diaries and su bmi tted a stool sample for pathogen carriage within 7 days of return . The study was powered to detect a 50 % reduction in the incidence of TD . RESULTS Of the 196 adults ( over 18 years of age ) enrolled in the study , 54.3 % were female and 80.9 % were younger than 60 years . The study r and omized 94 people to the AKSB arm and 102 to placebo . The incidence of TD was 54.5 % in the overall group with 55.3 % in the AKSB arm and 53.9 % in the placebo ( p = 0.8864 ) . Among the subjects who experienced diarrhea ( n = 107 ) there was no significant difference in the proportion of subjects that took antibiotics versus those that did not take antibiotics ( 35 % vs 29 % , p = 0.68 ) . AKSB was safe with no difference in toxicity between the two arms . CONCLUSIONS The prophylactic oral synbiotic was safe but did not reduce the risk of developing TD among travelers , nor did it decrease the duration of TD or the use of antibiotics when TD occurred |
2,171 | 24,843,701 | Conclusions The meta‐ analysis showed that non‐surgical periodontal treatment improves metabolic control in patients with both periodontitis and diabetes | Abstract Aims / Introduction The aim of the present study was to investigate whether non‐surgical periodontal treatment reduces glycated hemoglobin ( HbA1c ) and fasting plasma glucose ( FPG ) levels in diabetic patients . | BACKGROUND AND OBJECTIVE Several studies have shown that periodontitis can complicate the severity of diabetes by worsening the degree of glycemic control . The purpose of this study was to determine the effect of full-mouth tooth extraction on glycemic control among type 2 diabetic patients . MATERIAL AND METHODS A total of 58 patients with type 2 diabetes mellitus and advanced periodontitis who were requiring extraction of all remaining teeth were r and omized consecutively into treatment ( full-mouth tooth extraction ) and control groups ( no treatment ) . Eight patients were lost to follow-up or reported use of antibiotics , leaving 50 patients to be included in the analysis . All patients had all their remaining teeth in a hopeless condition . Relevant data were collected , and glycosylated hemoglobin ( HbA(1c ) ) and fasting blood glucose levels were measured at baseline and at follow-up times of 3 and 6 mo . RESULTS At baseline , the mean ( SD ) HbA(1c ) level was 8.6 % ( 1.24 ) in the treatment group and 7.7 % ( 0.87 ) in the control group . In the treatment group , the mean HbA(1c ) level decreased significantly from 8.6 % at baseline to 7.4 % after 3 mo of denture treatment , and continued to decrease to 7.3 % after 6 mo . In the control group , the mean HbA(1c ) decreased from 7.7 % at baseline to 7.5 % after 3 mo , and remained almost the same after 6 mo . After adjusting for the baseline HbA(1c ) , the mean reduction in HbA(1c ) after 3 mo in the treatment group [ 1.23 % ( 0.79 ) ] was significantly higher than the mean reduction in the control group [ 0.28 % ( 0.87 ) ] . CONCLUSION Full-mouth tooth extraction result ed in an improvement in glycemic control among diabetic patients . Large-scale multicentre clinical trials are needed to confirm the current evidence The aim of this study was to evaluate changes in clinical parameters and levels of inflammatory biomarkers in plasma in periodontal patients with poorly controlled type 2 diabetes mellitus ( T2DM ) after non-surgical periodontal therapy . Twenty-eight poorly controlled T2DM patients were r and omly assigned to treatment with scaling and root planning ( SRP ) and SRP + subgingival minocycline administration . Clinical parameters , including the probing depth ( PD ) , bleeding on probing ( BOP ) , plaque score ( PS ) , clinical attachment level ( CAL ) , and plasma interleukin (IL)-6 , soluble receptor of advanced glycation end products ( sRAGE ) , chronic reactive protein ( CRP ) , and hemoglobin A1c ( HbA1c ) were measured before and after a 6-month treatment period . Significant changes in PD , BOP , PS , and CAL were found in both groups . The latent growth curve model showed an overall reduction in the log HbA1c level in the SRP group ( −0.082 , p = 0.033 ) . Small changes in the log sRAGE level and log CRP level in plasma were found in both groups . IL-6 in the plasma increased in the SRP group , but slightly decreased in the SRP+minocycline group ( 0.469 pg/ml , p = 0.172 ) . Non-surgical periodontal therapy with or without subgingival minocycline application may achieve significant periodontal improvement and moderate improvement in HbA1c , but had no significant effect on plasma levels of IL-6 , CRP , or sRAGE in patients with poorly controlled T2DM . For patients with both periodontal diseases and diabetes , non-surgical periodontal treatments may be helpful in their diabetic control In vitro and animal studies suggest a possible role for the tetracycline class of drugs in the inhibition of non-enzymatic protein glycation . We conducted a 3-month , r and omized placebo-controlled pilot clinical trial of conventional sub-gingival debridement ( periodontal therapy ) , combined with either a three month regimen of sub-antimicrobial-dose doxycycline ( SDD ) , a two week regimen of antimicrobial-dose doxycycline ( ADD ) , or placebo in 45 patients with long-st and ing type 2 diabetes ( mean duration 9 years ) and untreated chronic periodontitis . Subjects were taking stable doses of oral hypoglycemic medications and /or insulin . Treatment response was assessed by measuring hemoglobin A1c ( HbA1c ) , plasma glucose , and clinical periodontal disease measures . At one-month and three-month follow-up , clinical measures of periodontitis were decreased in all groups ( data to be presented elsewhere ) . At three months , mean HbA1c levels in the SDD group were reduced 0.9 % units from 7.2 % units±2.2 ( ±SD ) , to 6.3 % units±1.1 , which represents a 12.5 % improvement . In contrast , there was no significant change in HbA1c in the ADD ( 7.5%±2.0 to 7.8%±2.1 ) or placebo ( 8.5%±2.0 to 8.5%±2.6 ) groups . Mean HbA1c change from baseline was significantly greater in the SDD group compared with the ADD group ( p=0.04 ) but not placebo ( p=0.22 ) . Moreover , a larger proportion of subjects in the SDD group experienced improvement ( p<0.05 ) compared to the ADD or placebo groups . Mean plasma glucose levels were not significantly different between or within the groups . The results of this pilot study suggest that the treatment of periodontitis with sub-gingival debridement and 3-months of daily sub-antimicrobial-dose doxycycline may decrease HbA1c in patients with type 2 diabetes taking normally prescribed hypoglycemic agents AIM To evaluate associations between glycaemic control and periodontitis progression among Gullah African Americans with type-2 diabetes mellitus ( T2DM ) . MATERIAL S AND METHODS From an ongoing clinical trial among T2DM Gullah , we extracted a cohort previously in a cross-sectional study ( N=88 ) . Time from baseline ( previous study ) to follow-up ( trial enrollment , before treatment interventions ) ranged 1.93 - 4.08 years [ mean=2.99 , st and ard deviation (SD)=0.36 ] . We evaluated tooth site-level periodontitis progression [ clinical attachment loss ( CAL ) worsening of > or = 2 mm , periodontal probing depth ( PPD ) increases of > or = 2 mm and bleeding on probing ( BOP ) from none to present ] by glycaemic control status ( well-controlled = HbA(1c)<7 % , poorly-controlled = HbA(1c ) > or = 7 % ) using multivariable generalized estimating equations logistic regression , nesting tooth sites/person . RESULTS Poorly-controlled T2DM ( 68.18 % ) was more prevalent than well-controlled T2DM ( 31.82 % ) . Proportions of tooth sites/person with CAL progression between baseline and follow-up ranged 0.00 - 0.59 ( mean=0.12 , SD=0.12 ) , while PPD and BOP progression ranged 0.00 - 0.44 ( mean=0.09 , SD=0.11 ) and 0.00 - 0.96 ( mean=0.24 , SD=0.18 ) , respectively . Site-level PPD at baseline was a significant effect modifier of associations between poorly-controlled T2DM and site-level CAL and PPD progression [ adjusted odds ratios ( OR ) according to poorly-controlled T2DM among PPD at baseline=3 , 5 and 7 mm , respectively : CAL progression=1.93 , 2.64 , and 3.62 , PPD progression=1.98 , 2.76 , and 3.84 ; p<0.05 for all ] . Odds of site-level BOP progression were increased ( OR=1.24 ) for poorly-controlled T2DM , yet the results were not significant ( p=0.32 ) . CONCLUSIONS These findings from a distinct , homogenous population further support the clinical relevance of identifying patients with poor glycaemic control and periodontitis , particularly among those with disparities for both diseases BACKGROUND Systemic inflammation may impair vascular function , and epidemiologic data suggest a possible link between periodontitis and cardiovascular disease . METHODS We r and omly assigned 120 patients with severe periodontitis to community-based periodontal care ( 59 patients ) or intensive periodontal treatment ( 61 ) . Endothelial function , as assessed by measurement of the diameter of the brachial artery during flow ( flow-mediated dilatation ) , and inflammatory biomarkers and markers of coagulation and endothelial activation were evaluated before treatment and 1 , 7 , 30 , 60 , and 180 days after treatment . RESULTS Twenty-four hours after treatment , flow-mediated dilatation was significantly lower in the intensive-treatment group than in the control-treatment group ( absolute difference , 1.4 % ; 95 % confidence interval [ CI ] , 0.5 to 2.3 ; P=0.002 ) , and levels of C-reactive protein , interleukin-6 , and the endothelial-activation markers soluble E-selectin and von Willebr and factor were significantly higher ( P<0.05 for all comparisons ) . However , flow-mediated dilatation was greater and the plasma levels of soluble E-selectin were lower in the intensive-treatment group than in the control-treatment group 60 days after therapy ( absolute difference in flow-mediated dilatation , 0.9 % ; 95 % CI , 0.1 to 1.7 ; P=0.02 ) and 180 days after therapy ( difference , 2.0 % ; 95 % CI , 1.2 to 2.8 ; P<0.001 ) . The degree of improvement was associated with improvement in measures of periodontal disease ( r=0.29 by Spearman rank correlation , P=0.003 ) . There were no serious adverse effects in either of the two groups , and no cardiovascular events occurred . CONCLUSIONS Intensive periodontal treatment result ed in acute , short-term systemic inflammation and endothelial dysfunction . However , 6 months after therapy , the benefits in oral health were associated with improvement in endothelial function Studies indicate that a dual pathway between diabetes mellitus and periodontal disease exists . Elimination of periodontal infection by using systemic antibiotics in conjunction with scaling and root planing ( SRP ) improved metabolic control in diabetic patients , as defined by reduction in glycated haemoglobin or reduction in insulin requirements ( Grossi and Genco , 1998 ) . The aim of this r and omised pilot clinical trial was to determine if type 1 diabetes patients with periodontitis will experience a reduction in HbA1c levels when treated with locally delivered minocycline microspheres ( Arestin ) as an adjunct to scaling and root planing . Twenty adult patients with poorly controlled diabetes ( HbA1c 7.5 % ) and adult periodontitis , as determined by the presence of four teeth with 5 mm periodontal pockets , two of which had 6 - 9 mm pockets and bleeding on probing , were included in the study . All patients received full mouth SRP at baseline . Arestin was administered to all pockets > or = > or = 5 mm at baseline and again at 12 weeks in the test group . Probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PI ) , gingival index ( GI ) , and HbA1c were evaluated at baseline and at weeks 6 , 12 , 18 and 24 . The results demonstrated that local administration of Arestin as an adjunct to scaling and root planing is significantly more effective in reducing probing depths and providing a gain in clinical attachment levels than scaling and root planing alone in type 1 diabetic patients . Hb1Ac was reduced in all patients ; however the difference between the test and control groups was not significant BACKGROUND Periodontitis , a complication of diabetes mellitus ( DM ) , can induce or perpetuate systemic conditions . This double-masked , placebo-controlled study evaluated the effects of periodontal therapy ( scaling and root planing [ SRP ] ) on the serum levels of glycated hemoglobin ( HbA1c ) and on inflammatory biomarkers . METHODS Thirty subjects with type 2 DM and periodontitis were treated with SRP + placebo ( SRP ; N = 15 ) or with SRP + doxycycline ( SRP+Doxy ; N = 15 ) , 100 mg/day , for 14 days . Clinical and laboratory data were recorded at baseline and at 3 months after treatment . RESULTS After 3 months , the reduction in probing depth was 0.8 mm for the SRP group ( P < 0.01 ) and 1.1 mm for the SRP+Doxy group ( P < 0.01 ) followed by a 0.9 % ( SRP ; P = 0.17 ) and 1.5 % ( SRP+Doxy ; P < 0.01 ) reduction in HbA1c levels . A significant reduction in interleukin (IL)-6 ; interferon-inducible protein 10 ; soluble fas lig and ; granulocyte colony-stimulating factor ; RANTES ; and IL-12 p70 serum levels were also verified ( N = 30 ) . To our knowledge , this is the first report on the effects of periodontal therapy on multiple systemic inflammatory markers in DM . CONCLUSIONS Periodontal therapy may influence the systemic conditions of patients with type 2 DM , but no statistical difference was observed with the adjunctive systemic doxycycline therapy . Moreover , it is possible that the observed improvement in glycemic control and in the reduction of inflammatory markers could also be due to diet , which was not controlled in our study . Therefore , a confirmatory study with a larger sample size and controlled diet is necessary AIMS : The purpose of this study is to investigate the effect of improved periodontal health on glycemic control in type 2 diabetes mellitus ( type 2 DM ) patients who have generalized periodontitis . MATERIAL S AND METHODS : A total of 45 type 2 DM patients with generalized periodontitis were selected for the study . The selected patients were r and omly assigned to three groups ( groups A , B , and C ) comprising 15 patients each : • Group A received treatment with scaling and root planing only . • Group B received treatment with scaling and root planing followed by systemic doxycycline . • Group C received no treatment ( control group ) . The periodontal parameters recorded included plaque index , gingival index , probing pocket depth , and clinical attachment level . These parameters were recorded at baseline ( day zero ) , at 1 month , and at the end of 3 months . The following metabolic parameters were recorded : fasting blood glucose ( FBG ) , postpr and ial blood glucose ( PPBG ) , and glycated hemoglobin . These were recorded at baseline ( day zero ) and at the end of 3 months . STATISTICAL ANALYSIS : All the parameters were subjected to repeated- measures ANOVA and Scheffe 's post hoc test . RESULTS : A statistically significant effect could be demonstrated for periodontal parameters for both group A and group B ( treatment groups ) . Glycated hemoglobin values showed statistically significant decrease in treatment groups compared to the control group , with group B showing more significant decrease than group A. CONCLUSIONS : The results of this study showed that nonsurgical periodontal treatment is associated with improved glycemic control in type 2 DM patients BACKGROUND Periodontitis is a major cause of tooth loss among adults . Several studies have shown a possible systemic impact of periodontal infection , including poor glycemic control in patients with diabetes . Recently , photodynamic therapy ( PDT ) was used to successfully treat periodontal infection . PDT provides a broad spectrum antimicrobial efficacy with no local or systemic side effects . The objective of this study was to examine the effect of the adjunctive use of PDT on periodontal status and glycemic control of patients with diabetes and periodontitis . METHODS Forty-five patients with type 2 diabetes and moderate to severe chronic periodontitis were selected and r and omly assigned to one of the following three treatment modalities ( 15 subjects each ) : scaling and root planing ( SRP ) only , SRP plus systemic doxycycline , and SRP plus PDT . The plaque and bleeding scores , probing depth , clinical attachment level , and glycosylated hemoglobin ( HbA1c ) level were recorded at baseline and 3 months after periodontal treatment . Descriptive statistics , the paired t test , and analysis of variance ( ANOVA ) were used for data analysis . RESULTS Statistically significant differences in the mean probing depth , clinical attachment level , plaque deposit , and bleeding on probing were found between baseline and 12 weeks post-treatment for all groups . No significant differences in periodontal parameters and glucose levels were detected among the three groups . Reduction in the mean HbA1c level after treatment was observed in all groups but was only significant for the SRP plus doxycycline group . CONCLUSION The results of the present study indicate that PDT does not benefit conventional non-surgical periodontal therapy in patients with diabetes BACKGROUND , AIMS This study was design ed to explore the effect of periodontal therapy on glycemic control in persons with type 2 diabetes mellitus ( DM ) . METHODS 36 patients with type 2 DM ( treatment group ) received therapy for adult periodontitis during an 18-month period . A 36-person control group was r and omly selected from the same population of persons with type 2 DM who did not receive periodontal treatment . RESULTS These groups were well matched for most of the parameters investigated . During the nine-month observation period , there was a 6.7 % improvement in glycemic control in the control group when compared to a 17.1 % improvement in the treatment group , a statistically significant difference . Several parameters that could confound or moderate this glycemic control were explored . These included the treatment of non-dental infections , weight and medication changes . No moderating effect was associated with any of these variables . However , there were too few subjects in the study to have the statistical power necessary to assess these possible moderators of glycemic control . CONCLUSIONS We interpret the data in the study to suggest that periodontal therapy was associated with improved glycemic control in persons with type 2 DM AIM The primary aim of this study was to examine the effects of intensive periodontal therapy on HbA(1c ) in a mixed diabetes mellitus ( DM ) ( types 1 and 2 ) population with moderate periodontitis ( PD ) . METHODS A total of 93 subjects with PD and DM , recruited from referrals to the Department of Endocrinology at the Perugia Hospital , were included in a follow-up cohort clinical study comprising two parallel periodontal therapy groups-one receiving intensive periodontal therapy ( IPT , n=44 ) and the other serving as controls ( CPT , n=49)-with an 8-month follow-up . Clinical periodontal examinations and blood sample s were collected 4 and 8 months after the completion of therapy . RESULTS The IPT group presented with greater reductions of all periodontal indices compared with the CPT group at both follow-ups ( P<0.001 ) . Whereas , after 4 months , there were no major differences in HbA(1c ) levels between groups , after 8 months , the IPT group presented with a 0.57 % ( 95 % CI : 0.12 to 1.09 ) greater reduction in HbA(1c ) than the CPT group ( P=0.03 ) . This reduction was independent of age , gender , smoking and body mass index . However , the difference in HbA(1c ) was greater in individuals with type 2 DM ( 0.95 % reduction , 95 % CI : 0.32 to 1.58 ; P=0.004 ) compared with those with type 1 DM . CONCLUSION IPT result ed in greater improvement of gingival health in patients with DM . Improved oral health in those with type 2 DM may have an effect on medium-term glucose management and could possibly lead to long-term health benefits . ( IS RCT N00559156 ) BACKGROUND The literature suggests that an alteration in glucose metabolism occurs as a result of antibacterial periodontal therapy . The objective of this study was to monitor the effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus ( DM ) . METHODS Thirty type 2 DM subjects with periodontitis were r and omly divided into two groups . Group 1 ( G1 ) , 15 subjects , received one-stage full-mouth scaling and root planing ( FMSRP ) plus amoxicillin/clavulanic acid 875 mg ; group 2 ( G2 ) , 15 patients , received only FMSRP . At baseline and after 3 months , the glycated hemoglobin ( HbA1c ) values , fasting glucose , and clinical parameters ( with computerized probing and individualized acrylic stents ) were recorded . Following therapy , the subjects were enrolled in a 2-week interval maintenance program for 3 months . RESULTS After treatment , both groups showed clinical improvements . A probing depth ( PD ) reduction of 0.8 + /- 0.6 mm ( P < 0.05 ) occurred in G1 and 0.9 + /- 0.4 mm in G2 ( P < 0.05 ) , but there were no significant changes in attachment level . Treatment reduced the HbA1c values after the 3-month observation period in both groups ; however , the reduction in HbA1c values for the G2 group was statistically significant , but not for the G1 group . The changes in fasting glucose levels were not significant for either group . CONCLUSIONS Periodontal therapy improved glycemic control in patients with type 2 DM in both groups ; however , the reduction in HbA1c values reached statistical significance only in the group receiving scaling and root planing alone [ correction ] AIM The purpose of this study was to assess the response of diabetics to scaling and root planing treatment and subgingival oral irrigation as adjunctive therapy . METHOD A total of 52 type 1 and 2 diabetics ( mean age 51.3+/-14 ) with adult periodontitis were r and omized to two groups . Treatment included ultrasonic scaling and scaling and root planing in both groups ( control and test ) plus subgingival water irrigation 2x daily for the test group . Assessment s were made prior to and at 6 and 12 weeks after treatment . Parameters measured were modified gingival index ( MGI ) , probing pocket depth ( PPD ) , plaque index ( PI ) , clinical attachment level ( CAL ) , and bleeding on probing ( BOP ) . Systemic measurement of Reactive Oxygen Species ( ROS ) generation , cytokines ( TNF-alpha , IL-1beta , IL-10 , and PGE2 ) , and glycated hemoglobin ( HbA1C ) . RESULTS After treatment , analysis of data showed that both groups had clinical and systemic improvement . The test group had a statistically significant reduction for MGI , PI , and BOP compared to controls ( p<0.03 ) at 12 weeks and for ROS generation at 12 weeks ( p<0.012 ) . Unlike controls , systemic analysis of cytokines showed a statistically significant reduction from baseline for IL-1beta at 6 weeks and PGE2 at 6 and 12 weeks ( p<0.05 ) within test group . CONCLUSION These results suggest that scaling and root planing and adjunctive therapy may be of value in establishing a healthy periodontium in diabetics OBJECTIVES Report results of a r and omized- clinical trial of the efficacy of periodontal care in the improvement of glycemic control in 165 veterans with poorly controlled diabetes over 4 months . METHODS Outcomes were change in Haemoglobin A1c ( HbA1c ) in the Early Treatment versus untreated ( Usual Care ) groups and percent of participants with decreases in HbA1c . Analyses included simple/multiple variable linear/logistic regressions , adjusted for baseline HbA1c , age , and duration of diabetes . RESULTS Unadjusted analyses showed no differences between groups . After adjustment for baseline HbA1c , age , and diabetes duration , the mean absolute HbA1c change in the Early Treatment group was -0.65 % versus -0.51 % in the Usual Care group ( p=0.47 ) . Adjusted odds for improvement by 0.5 % in the Early Treatment group was 1.67 ( 95 % confidence interval : 0.84 , 3.34 , p=0.14 ) . Usual Care subjects were twice as likely to increase insulin from baseline to 4 months ( 20 % versus 11 % , p=0.12 ) and less likely to decrease insulin ( 1 % versus 6 % , p=0.21 ) than Early Treatment subjects . Among insulin users at baseline , more increased insulin in the Usual Care group ( 40 % versus 21 % , p=0.06 ) . CONCLUSIONS No significant benefit was found for periodontal therapy after 4 months in this study ; trends in some results were in favour of periodontal treatment OBJECTIVE The aim of this study was to find out if periodontal therapy has any effect on glycemic control of type 1 diabetes mellitus ( DM ) . SUBJECTS AND METHODS The periodontal health status of 65 type 1 diabetic subjects was assessed at the baseline and 8 weeks after completion of periodontal therapy . Glycemic control was assessed on both visits by measuring the percentage of glycosylated haemoglobin ( GHbA1c ) . The change in HbA1c ( DeltaHbA1c ) was assessed by using both a positive or negative change > or=0.5 % and any change in HbA1c . RESULTS The mean HbA1c level ( + /-SD ) of the whole study group was 8.6 % ( + /-1.5 ) at the baseline and 8.5 % ( + /-1.5 ) after treatment . Glycemic control improved during the study period in 23 subjects ( 35 % ) and worsened in 18 subjects ( 28 % ) . Approximately 78 % of the bleeding sites and 87 % of the sites with probing depth > or=4 mm presented healing . DeltaHbA1c associated significantly with baseline HbA1c but not with baseline periodontal health status or periodontal healing . CONCLUSION Regardless of a significant resolution of periodontal infection , a great majority of the subjects did not present any improvement in their glycemic control BACKGROUND Alendronate ( ALN ) is an aminobisphosphonate commonly used for osteoporosis in postmenopausal women . We studied the effect of ALN on bone loss prevention in type 2 diabetes mellitus patients with periodontal disease . METHODS In a controlled double-blind , r and omized study we evaluated prospect ively diabetic patients paired by gender and years since diagnosis for 6 months . The study included 40 patients ( 20 men and 20 women ) , 50 to 60 years old , with more than 5 years since diagnosis of diabetes and established periodontitis . They were r and omly allocated to alendronate ( 10 mg/daily ) or placebo treatment for 6 months . The endpoints of treatment were : the distance between the alveolar bone border and the cemento-enamel-junction ( CEJ ) evaluated by means of digital radiographic imaging , a biochemical marker of bone resorption ( urine N-telopeptide ) ( Ntx ) , and periodontal parameters . Metabolic control was assessed at baseline and after 6 months . RESULTS Baseline and 6-month glycated hemoglobin levels were similar in both groups . Alendronate induced a significant decrease in NTx at 6 months ( P = 0.006 ) . Periodontal parameters improved in both groups . However , they were significantly better for the ALN treated group . Alveolar bone border-CEJ distance increased in the placebo , but decreased in the ALN group ( P = 0.0003 ) . CONCLUSIONS In type-2 diabetic patients , alendronate induced more improvement in alveolar bone crest height than control therapy . No differences in urinary N-telopeptide or glycated hemoglobin were observed in this short-term r and omized controlled pilot trial AIMS The aims of this study were to evaluate the effect of mechanical periodontal treatment with local application of minocycline ( APT ) on serum adiponectin as a marker of insulin resistance improvement in type 2 diabetes mellitus ( T2DM ) patients and to investigate if effect of APT on serum adiponectin level was sustained by periodontal maintenance ( PM ) . MATERIAL AND METHODS Twenty-seven T2DM patients were r and omly assigned into test or control groups . Test received scaling with ultrasonic devices at baseline and APT biweekly for 2 months while control received scaling at baseline and mechanical tooth cleaning ( MPT ) at the same interval . At 6 months , all patients received mechanical tooth cleaning as PM . Periodontal examination and blood measurements were performed at baseline , 4 and 9 months . RESULTS Adiponectin concentrations in test had significantly increased by 31.4 % after APT ( p=0.024 ) and by 30.4 % after PM ( p=0.002 ) compared with baseline . The percentage of > or=4 mm probing depths ( PD ) had shown 8.3 % and 9.3 % reduction after APT and PM ( p=0.046 , 0.02 ) in test while 5.0 % reduction after MPT in control group ( p=0.031 ) . CONCLUSIONS Our results suggested that APT and PM not only improve periodontal disease but also increase serum adiponectin in T2DM patients |
2,172 | 28,893,758 | Tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine , but certainty is low when they are not coprescribed with lopinavir/ritonavir .
Other outcomes are likely similar between antiretrovirals . | OBJECTIVE To assess the impact of various antiretroviral/antiviral regimens in pregnant women living with HIV or hepatitis B virus ( HBV ) . | This r and omized , double-blind , placebo-controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus ( HBV ) perinatal transmission in highly viraemic mothers . Mothers were r and omized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum . At birth , infants received recombinant HBV vaccine with or without HBIg and were followed until week 52 . One hundred and fifty mothers , with a gestational age of 26 - 30 weeks and serum HBV DNA > 1000 MEq/mL ( bDNA assay ) , were treated . A total of 141 infants received immunoprophylaxis at birth . In lamivudine-treated mothers , 56 infants received vaccine + HBIg ( lamivudine + vaccine + HBIg ) and 26 infants received vaccine ( lamivudine + vaccine ) . In placebo-treated mothers , 59 infants received vaccine + HBIg ( placebo + vaccine + HBIg ) . At week 52 , in the primary analyses where missing data was counted as failures , infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity ( 10/56 , 18%vs 23/59 , 39 % ; P = 0.014 ) and in detectable HBV DNA ( 11/56 , 20%vs 27/59 , 46 % ; P = 0.003 ) compared to infants in the placebo + vaccine + HBIg group . Sensitivity analyses to evaluate the impact of missing data at week 52 result ing from a high dropout rate ( 13 % in the lamivudine + vaccine + HBIg group and 31 % in the placebo + vaccine + HBIg group ) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers , but the differences were not statistically significant . No safety concerns were noted in the lamivudine-treated mothers or their infants . Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization Thomas Campbell and colleagues report findings of a r and omized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing # # # What you need to know What is the role of arthroscopic surgery in degenerative knee disease ? An expert panel produced these recommendations based on a linked systematic review triggered by a r and omised trial published in The BMJ in June 2016 , which found that , among patients with a degenerative medial meniscus tear , knee arthroscopy was no better than exercise therapy . The panel make a strong recommendation against arthroscopy for degenerative knee disease . Box 1 shows all of the articles and evidence linked in this Rapid Recommendation package . The infographic provides an overview of the absolute benefits and harms of arthroscopy in st and ard GRADE format . Table 1 below shows any evidence that has emerged since the publication of this article . Box 1 # # # Linked articles in this BMJ Rapid Recommendations BACKGROUND In sub-Saharan Africa , the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high . We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy ( ART ) , 6-month isoniazid preventive therapy ( IPT ) , or both among HIV-infected adults with high CD4 + cell counts in Ivory Coast . METHODS We included participants who had HIV type 1 infection and a CD4 + count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization ( WHO ) guidelines . Participants were r and omly assigned to one of four treatment groups : deferred ART ( ART initiation according to WHO criteria ) , deferred ART plus IPT , early ART ( immediate ART initiation ) , or early ART plus IPT . The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome ( AIDS ) , non-AIDS-defining cancer , non-AIDS-defining invasive bacterial disease , or death from any cause at 30 months . We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies . RESULTS A total of 2056 patients ( 41 % with a baseline CD4 + count of ≥500 cells per cubic millimeter ) were followed for 4757 patient-years . A total of 204 primary end-point events were observed ( 3.8 events per 100 person-years ; 95 % confidence interval [ CI ] , 3.3 to 4.4 ) , including 68 in patients with a baseline CD4 + count of at least 500 cells per cubic millimeter ( 3.2 events per 100 person-years ; 95 % CI , 2.4 to 4.0 ) . Tuberculosis and invasive bacterial diseases accounted for 42 % and 27 % of primary end-point events , respectively . The risk of death or severe HIV-related illness was lower with early ART than with deferred ART ( adjusted hazard ratio , 0.56 ; 95 % CI , 0.41 to 0.76 ; adjusted hazard ratio among patients with a baseline CD4 + count of ≥500 cells per cubic millimeter , 0.56 ; 95 % CI , 0.33 to 0.94 ) and lower with IPT than with no IPT ( adjusted hazard ratio , 0.65 ; 95 % CI , 0.48 to 0.88 ; adjusted hazard ratio among patients with a baseline CD4 + count of ≥500 cells per cubic millimeter , 0.61 ; 95 % CI , 0.36 to 1.01 ) . The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies . CONCLUSIONS In this African country , immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT , both overall and among patients with CD4 + counts of at least 500 cells per cubic millimeter . ( Funded by the French National Agency for Research on AIDS and Viral Hepatitis ; TEMPRANO ANRS 12136 Clinical Trials.gov number , NCT00495651 . ) BACKGROUND The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors ( NRTIs ) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which NRTI combination has greater efficacy and safety is not known . METHODS In a r and omized , blinded equivalence study involving 1858 eligible patients , we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection : abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir . The primary efficacy end point was the time from r and omization to virologic failure ( defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks , or > or = 200 copies per milliliter at or after 24 weeks ) . RESULTS A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy , according to the NRTI combination , among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more . At a median follow-up of 60 weeks , among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group ( hazard ratio , 2.33 ; 95 % confidence interval , 1.46 to 3.72 ; P<0.001 ) , with 57 virologic failures ( 14 % ) in the abacavir-lamivudine group versus 26 ( 7 % ) in the tenofovir DF-emtricitabine group . The time to the first adverse event was also shorter in the abacavir-lamivudine group ( P<0.001 ) . There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48 . CONCLUSIONS In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the times to virologic failure and the first adverse event were both significantly shorter in patients r and omly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine . ( Clinical Trials.gov number , NCT00118898 . OBJECTIVE To compare the efficacy and safety of fixed-dose abacavir/lamivudine ( ABC/3TC ) and tenofovir/emtricitabine ( TDF/FTC ) with ritonavir-boosted atazanavir ( ATV/r ) in treatment-naïve Japanese patients with HIV-1 infection . METHODS A 96-week multicenter , r and omized , open-label , parallel group pilot study was conducted . The endpoints were times to virologic failure , safety event and regimen modification . RESULTS 109 patients were enrolled and r and omly allocated ( 54 patients received ABC/3TC and 55 patients received TDF/FTC ) . All r and omized subjects were analyzed . The time to virologic failure was not significantly different between the two arms by 96 weeks ( HR , 2.09 ; 95 % CI , 0.72 - 6.13 ; p=0.178 ) . Both regimens showed favorable viral efficacy , as in the intention-to-treat population , 72.2 % ( ABC/3TC ) and 78.2 % ( TDF/FTC ) of the patients had an HIV-1 viral load < 50 copies/mL at 96 weeks . The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms ( adverse event : HR 0.66 ; 95 % CI , 0.25 - 1.75 , p=0.407 ) ( regimen modification : HR 1.03 ; 95 % CI , 0.33 - 3.19 , p=0.964 ) . Both regimens were also well-tolerated , as only 11.1 % ( ABC/3TC ) and 10.9 % ( TDF/FTC ) of the patients discontinued the allocated regimen by 96 weeks . Clinical ly suspected abacavir-associated hypersensitivity reactions occurred in only one ( 1.9 % ) patient in the ABC/3TC arm . CONCLUSION Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC , this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients , such as the Japanese population BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus ( HIV ) infection in some trials but not in others . METHODS In this r and omized , double-blind , placebo-controlled trial , we assigned 2120 HIV-negative women in Kenya , South Africa , and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or placebo once daily . The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety . RESULTS HIV infections occurred in 33 women in the TDF-FTC group ( incidence rate , 4.7 per 100 person-years ) and in 35 in the placebo group ( incidence rate , 5.0 per 100 person-years ) , for an estimated hazard ratio in the TDF-FTC group of 0.94 ( 95 % confidence interval , 0.59 to 1.52 ; P=0.81 ) . The proportions of women with nausea , vomiting , or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group ( P=0.04 , P<0.001 , and P=0.03 , respectively ) . Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group ( 4.7 % ) than in the placebo group ( 3.0 % , P=0.051 ) . Less than 40 % of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion . The study was stopped early , on April 18 , 2011 , because of lack of efficacy . CONCLUSIONS Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects , as compared with placebo . Despite substantial counseling efforts , drug adherence appeared to be low . ( Supported by the U.S. Agency for International Development and others ; FEM-PrEP Clinical Trials.gov number , NCT00625404 . ) OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as " probably done " or " probably not done . " STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were " definitely yes , " " probably yes , " " probably no , " and " definitely no. " We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of " probably yes " and " probably no " instead of " unclear " may enhance the assessment of blinding in trials OBJECTIVE To investigate the effect of high viral loads ( HBV DNA concentration in blood > 2.0 copy/ml ) on the vertical transmission of hepatitis B virus in mothers with HBV DNA positivity . METHOD Forty pregnant women with HBV DNA positivity were divided r and omly , double-blindly into 2 groups : at 28 weeks of pregnancy , one group received oral lamivudine ( 100 mg/d ) and the other received oral placebo . The serum HBV DNA loads were tested at 28 and 40 weeks ' gestation in mothers , and serum HBV DNA , HBsAg , HBeAg and anti-HBs were examined in infants at 12 month follow up . RESULT Thirty-nine infants finished ( one twins ) the follow up , and 2 infants lost ( 5 % ) . Among them 4 infants were confirmed to be HBV infection ( 10 % , 4/39 ) , 2 in the treatment group ( 10 % , 2/20 ) and 2 in the control group ( 11 % , 2/19 ) ( P > 0.05 ) . The serum HBV DNA levels of 40 weeks ' gestation in the treatment group , compared with the levels of 28 weeks ' gestation in the treatment group and 40 weeks ' gestation in the control group , showed a significant decline ( P < 0.01 ) . The HBV DNA levels of the mothers whose infants were infected , were ( 3.1 + /- 3.4 ) copy/ml , ( 3.1 + /- 3.2 ) copy/ml during 28 and 40 weeks ' gestation , and for mothers whose infants were non-infected , the levels were ( 3.4 + /- 2.2 ) copy/ml , ( 2.6 + /- 1 . 5 ) copy/ml respectively ( P > 0.05 ) . The mean values of anti-HBs of 18 infants in the treatment group showed no significant difference as compared to 17 infants in the control group , ( 594 + /- 416 ) U/L vs ( 458 + /- 398 ) U/L ( P > 0.05 ) . CONCLUSION The pregnant women 's HBV DNA loads could be obviously decreased from high viral loads ( HBV DNA concentrations in blood > 2.0 copy/ml ) after they take lamivudine from 36 weeks ' gestation . But it might not reduce the maternal-fetal vertical transmission of HBV infection IMPORTANCE Antiretroviral preexposure prophylaxis ( PrEP ) , using tenofovir disoproxil fumarate ( TDF ) and combination emtricitabine/tenofovir disoproxil fumarate ( FTC+TDF ) , is efficacious for prevention of human immunodeficiency virus ( HIV ) acquisition . PrEP could reduce periconception HIV risk , but the effect on pregnancy outcomes is not well defined . OBJECTIVE To assess pregnancy incidence and outcomes among women using PrEP during the periconception period . DESIGN , SETTING , AND PARTICIPANTS R and omized trial among 1785 HIV-serodiscordant heterosexual couples ( the Partners PrEP Study ) in which the female partner was HIV uninfected that demonstrated that PrEP was efficacious for HIV prevention , conducted between July 2008 and June 2013 at 9 sites in Kenya and Ug and a. INTERVENTIONS Daily oral TDF ( n = 598 ) , combination FTC+TDF ( n = 566 ) , or placebo ( n = 621 ) through July 2011 , when PrEP demonstrated efficacy for HIV prevention . Thereafter , participants continued receiving active PrEP without placebo . Pregnancy testing occurred monthly and study medication was discontinued when pregnancy was detected . MAIN OUTCOMES AND MEASURES Pregnancy incidence , birth outcomes ( live births , pregnancy loss , preterm birth , congenital anomalies ) , and infant growth . RESULTS A total of 431 pregnancies occurred . Pregnancy incidence was 10.0 per 100 person-years among women assigned placebo , 11.9 among those assigned TDF ( incidence difference , 1.9 ; 95 % CI , -1.1 to 4.9 [ P = .22 vs placebo ] ) , and 8.8 among those assigned FTC+TDF ( incidence difference , -1.3 ; 95 % CI , -4.1 to 1.5 [ P = .39 vs placebo ] ) . Before discontinuation of the placebo treatment group in July 2011 , the occurrence of pregnancy loss ( 96 of 288 pregnancies ) was 42.5 % for women receiving FTC+TDF compared with 32.3 % for those receiving placebo ( difference for FTC+TDF vs placebo , 10.2 % ; 95 % CI , -5.3 % to 25.7 % ; P = .16 ) and was 27.7 % for those receiving TDF alone ( difference vs placebo , -4.6 % ; 95 % CI , -18.1 % to 8.9 % ; P = .46 ) . After July 2011 , the frequency of pregnancy loss ( 52 of 143 pregnancies ) was 37.5 % for FTC+TDF and 36.7 % for TDF alone ( difference , 0.8 % ; 95 % CI , -16.8 % to 18.5 % ; P = .92 ) . Occurrence of preterm birth , congenital anomalies , and growth throughout the first year of life did not differ significantly for infants born to women who received PrEP vs placebo . CONCLUSIONS AND RELEVANCE Among HIV-serodiscordant heterosexual African couples , differences in pregnancy incidence , birth outcomes , and infant growth were not statistically different for women receiving PrEP with TDF alone or combination FTC+TDF compared with placebo at conception . Given that PrEP was discontinued when pregnancy was detected and that CIs for the birth outcomes were wide , definitive statements about the safety of PrEP in the periconception period can not be made . These results should be discussed with HIV-uninfected women receiving PrEP who are considering becoming pregnant . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00557245 BACKGROUND Few data are available regarding the use of tenofovir disoproxil fumarate ( TDF ) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus ( HBV ) . METHODS In this trial , we included 200 mothers who were positive for hepatitis B e antigen ( HBeAg ) and who had an HBV DNA level higher than 200,000 IU per milliliter . Participants were r and omly assigned , in a 1:1 ratio , to receive usual care without antiviral therapy or to receive TDF ( at an oral dose of 300 mg per day ) from 30 to 32 weeks of gestation until postpartum week 4 ; the participants were followed until postpartum week 28 . All the infants received immunoprophylaxis . The primary outcomes were the rates of mother-to-child transmission and birth defects . The secondary outcomes were the safety of TDF , the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery , and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28 . RESULTS At delivery , 68 % of the mothers in the TDF group ( 66 of 97 women ) , as compared with 2 % in the control group ( 2 of 100 ) , had an HBV DNA level of less than 200,000 IU per milliliter ( P<0.001 ) . At postpartum week 28 , the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group , both in the intention-to-treat analysis ( with transmission of virus to 5 % of the infants [ 5 of 97 ] vs. 18 % [ 18 of 100 ] , P=0.007 ) and the per- protocol analysis ( with transmission of virus to 0 vs. 7 % [ 6 of 88 ] , P=0.01 ) . The maternal and infant safety profiles were similar in the TDF group and the control group , including birth-defect rates ( 2 % [ 2 of 95 infants ] and 1 % [ 1 of 88 ] , respectively ; P=1.00 ) , although more mothers in the TDF group had an increase in the creatine kinase level . After the discontinuation of TDF , alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group ( 45 % [ 44 of 97 women ] vs. 30 % [ 30 of 100 ] , P=0.03 ) . The maternal HBV serologic outcomes did not differ significantly between the groups . CONCLUSIONS In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester , the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy . ( Funded by Gilead Sciences ; Clinical Trials.gov number , NCT01488526 . ) BACKGROUND AIDS Clinical Trials Group A5202 compared blinded abacavir/lamivudine ( ABC/3TC ) to tenofovir DF/emtricitabine ( TDF/FTC ) with efavirenz ( EFV ) or atazanavir/ritonavir ( ATV/r ) in human immunodeficiency virus (HIV)-infected treatment-naive patients , stratified by screening HIV RNA ( < or ≥ 10(5 ) copies/mL ) . Due to higher virologic failure with ABC/3TC in the high HIV RNA stratum , blinded treatment was stopped in this group , but study follow-up continued for all patients . METHODS Primary endpoints were times to virologic failure , regimen modification , and safety event . RESULTS In the low HIV RNA stratum , time to virologic failure was similar for ABC/3TC vs TDF/FTC with ATV/r ( hazard ratio [ HR ] 1.25 , 95 % confidence interval [ CI ] 0.76 , 2.05 ) or EFV ( HR 1.23 , 95 % CI 0.77 , 1.96 ) , with significantly shorter times to regimen modification for ABC/3TC with EFV or ATV/r and to safety events with EFV . Prior to stopping blinded treatment in the high stratum , higher virologic failure rates were seen with ABC/3TC with EFV ( HR 2.46 , 95 % CI 1.20 , 5.05 ) or ATV/r ( HR 2.22 , 95 % CI 1.19 , 4.14 ) . CONCLUSIONS In the low HIV RNA stratum , times to virologic failure for ABC/3TC or TDF/FTC were not different with EFV or ATV/r . In the high stratum , virologic failure rate was significantly higher for ABC/3TC than for TDF/FTC when given with either EFV or ATV/r Objective : Reduced lopinavir concentrations have been demonstrated with use of the capsule formulation during the third trimester of pregnancy . This study determined lopinavir exposure with an increased dose of the new tablet formulation during the third trimester . Design : International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is a prospect i ve nonblinded pharmacokinetic study in HIV-infected pregnant women , including a cohort receiving 2 lopinavir/ritonavir tablets ( 400 mg/100 mg ) twice daily during the second trimester , 3 tablets ( 600 mg/150 mg ) twice daily during the third trimester , and 2 tablets ( 400 mg/100 mg ) twice daily postdelivery through 2 weeks postpartum . Methods : Steady-state 12-hour pharmacokinetic profiles were performed during pregnancy and at 2 weeks postpartum . Lopinavir and ritonavir were measured by reverse-phase high-performance liquid chromatography ( detection limit , 0.09 mcg/mL ) . Results : Thirty-three women were studied . Median lopinavir AUC for the second trimester ( n = 11 ) , third trimester ( n = 33 ) , and postpartum ( n = 27 ) were 72 , 96 , and 133 mcg·hr/mL , respectively . Median minimum lopinavir concentrations were 3.4 , 4.9 , and 6.9 mcg/mL. Conclusions : The higher lopinavir/ritonavir tablet dose ( 600 mg/150 mg ) provided exposure during the third trimester similar to the average AUC ( 98 mcg·hr·mL−1 ) in nonpregnant adults taking 400 mg/100 mg twice daily . The higher dose should be used during the second and third trimesters of pregnancy . Postpartum dosing can be reduced to st and ard dosing before 2 weeks postpartum BACKGROUND AND OBJECTIVES : Perinatal exposure is an important mode of hepatitis B virus ( HBV ) transmission , result ing in chronic disease in ∼90 % of infected infants . Immunoprophylaxis recommended for infants born to hepatitis B surface antigen – positive mothers reduces up to 95 % of perinatal HBV infections . We sought to identify factors associated with perinatal HBV transmission . METHODS : We analyzed prospect ively collected data from 5 of 64 US-funded Perinatal Hepatitis B Prevention Programs during 2007–2013 . We examined effects of maternal demographic and laboratory results , infant gestational age and birth weight , and immunoprophylactic management on perinatal HBV infection . RESULTS : Data from 17 951 mother-infant pairs were analyzed . Among 9252 ( 51.5 % ) infants for whom hepatitis B surface antigen testing results were available , 100 ( 1.1 % ) acquired perinatal HBV infection . Both hepatitis B ( HepB ) vaccine and hepatitis B immune globulin were administered within 12 hours of birth for 10 760 ( 94.9 % ) of 11 335 infants with information . Perinatal HBV infection was associated with younger maternal age ( P = .01 ) , Asian/Pacific Isl and er race ( P < .01 ) , maternal hepatitis B e-antigen positivity ( P < .01 ) , maternal antibody to hepatitis B e-antigen negativity ( P < .01 ) , maternal viral load ≥2000 IU/mL ( P = .04 ) , and infant receipt of <3 HepB vaccine doses ( P = .01 ) . Four infants born to 429 mothers with viral load testing were infected ; all 4 were born to mothers with viral loads in the ninth or tenth decile . CONCLUSIONS : Perinatal HBV infection occurred among 1 % of infants , most of whom received recommended immunoprophylaxis . Infants at greatest risk of infection were those born to women who were younger , hepatitis B e-antigen positive , or who had a high viral load or those infants who received <3 HepB vaccine doses BACKGROUND Durable suppression of replication of the human immunodeficiency virus ( HIV ) depends on the use of potent , well-tolerated antiretroviral regimens to which patients can easily adhere . METHODS We conducted an open-label , noninferiority study involving 517 patients with HIV infection who had not previously received antiretroviral therapy and who were r and omly assigned to receive either a regimen of tenofovir disoproxil fumarate ( DF ) , emtricitabine , and efavirenz once daily ( tenofovir-emtricitabine group ) or a regimen of fixed-dose zidovudine and lamivudine twice daily plus efavirenz once daily ( zidovudine-lamivudine group ) . The primary end point was the proportion of patients without baseline resistance to efavirenz in whom the HIV RNA level was less than 400 copies per milliliter at week 48 of the study . RESULTS Through week 48 , significantly more patients in the tenofovir-emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine-lamivudine group ( 84 percent vs. 73 percent , respectively ; 95 percent confidence interval for the difference , 4 to 19 percent ; P=0.002 ) . This difference excludes the inferiority of the tenofovir DF , emtricitabine , and efavirenz regimen , indicating a significantly greater response with this regimen . Significant differences were also seen in the proportion of patients with HIV RNA levels of less than 50 copies per milliliter ( 80 percent in the tenofovir-emtricitabine group vs. 70 percent in the zidovudine-lamivudine group ; 95 percent confidence interval for the difference , 2 to 17 percent ; P=0.02 ) and in increases in CD4 cell counts ( 190 vs. 158 cells per cubic millimeter , respectively ; 95 percent confidence interval for the difference , 9 to 55 ; P=0.002 ) . More patients in the zidovudine-lamivudine group than in the tenofovir-emtricitabine group had adverse events result ing in discontinuation of the study drugs ( 9 percent vs. 4 percent , respectively ; P=0.02 ) . In none of the patients did the K65R mutation develop . CONCLUSIONS Through week 48 , the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression , CD4 response , and adverse events result ing in discontinuation of the study drugs . ( Clinical Trials.gov number , NCT00112047 . BACKGROUND There is limited information on antiviral therapy for hepatitis B virus ( HBV ) infection among pregnant women coinfected with human immunodeficiency virus ( HIV ) and HBV . METHODS A phase 2 r and omized , controlled trial of a regimen containing tenofovir (TDF)/lamivudine ( 3TC ) and a regimen containing 3TC in HIV/HBV-coinfected pregnant women in China . The HBV virological response was compared in study arms . RESULTS The median decline in the HBV DNA level was 2.60 log10 copies/mL in the TDF/3TC arm and 2.24 log10 copies/mL in the 3TC arm ( P = .41 ) . All women achieved HBV DNA levels of < 6 log10 copies/mL at delivery . CONCLUSIONS Initiation of either regimen led to achievement of HBV DNA levels below the threshold associated with perinatal HBV transmission . CLINICAL TRIALS REGISTRATION NCT01125696 Background : Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies , yet few studies have comprehensively compared their safety profiles . Methods : Forty-eight-week data are presented from this multicenter , r and omized , open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine , both administered with efavirenz , in HLA-B*5701-negative HIV-1-infected adults . Results : Three hundred eighty-five subjects were enrolled in the study . The overall rate of withdrawal was high ( 28 % ) . Changes in estimated glomerular filtration rate from baseline were similar between arms [ difference 0.953 mL·min−1·1.73 m−2 ( 95 % confidence interval : −1.445 to 3.351 ) , P = 0.435 ] . Urinary excretion of retinol-binding protein and β-2 microglobulin increased significantly more in the tenofovir/emtricitabine arm ( + 50 % ; + 24 % ) compared with the abacavir/lamivudine arm ( no change ; −47 % ) ( P < 0.0001 ) . A lower proportion achieved viral load < 50 copies per milliliter in the abacavir/lamivudine arm ( 114 of 192 , 59 % ) compared with the tenofovir/emtricitabine arm ( 137 of 193 , 71 % ) [ difference 11.6 % ( 95 % confidence interval : 2.2 to 21.1 ) ] . The overall virological failure rate was low . The adverse event rate was similar between arms ( except drug hypersensitivity , reported more in the abacavir/lamivudine arm ) . Conclusions : The study showed no difference in estimated glomerular filtration rate between the arms , however , increases in markers of tubular dysfunction were observed in the tenofovir/emtricitabine arm , the long-term consequence of which is unclear . A significant difference in efficacy favoring tenofovir/emtricitabine was observed Objective : Lopinavir/ritonavir ( LPV/r ) and tenofovir disoproxil fumarate ( TDF ) are frequently used antiretrovirals . A pharmacokinetic study in healthy volunteers was conducted to assess the potential for a drug interaction between these agents . Methods : This was a 36-day , multiple-dose , drug-drug interaction study of TDF and lopinavir/ritonavir ( LPV/r ) . Subjects received TDF alone for 7 days , followed by 14 days each of TDF plus LPV/r and LPV/r alone in a r and omized manner . Pharmacokinetic assessment s were performed over 24 hours on days 7 , 21 , and 35 . LPV/r and tenofovir plasma/serum concentrations were measured by high-performance liquid chromatography/mass spectometry (MS)/MS . Geometric mean ratios and 90 % confidence intervals of pharmacokinetic parameters for tenofovir , LPV , and ritonavir ( RTV ) were estimated using analysis of variance and compared with the no-effect criterion for pharmacokinetic equivalence . Results : Tenofovir measurements with an area under the concentration-time curve over the dosing interval , maximum concentration , and concentration at the end of the dosing interval ( Cτ ) were 32 % , 15 % , and 51 % higher , respectively , when TDF was coadministered with LPV/r ( n = 24 ) . LPV and RTV pharmacokinetics , including Cτ , were unaffected by TDF ( n = 24 ) . Clinical estimates of renal function were unaffected by administration of TDF alone or with LPV/r . Discussion : Coadministration of TDF with LPV/r result ed in increased tenofovir exposures at steady state , possibly through increased absorption . This increase is not believed to be clinical ly relevant based on the safety and efficacy of TDF plus LPV/r-containing regimens in HIV-infected patients in long-term controlled clinical trials This study sought to assess the antiviral efficacy of lamivudine ( LMV ) administered during third trimester to reduce maternal viraemia and to identify the emergence of LMV resistance . A prospect i ve observational analysis was performed on 26 mothers with high viral load ( > 10⁷ IU/mL ) . Twenty-one women received LMV ( treated group ) for an average of 53 days ( range 22 - 88 days ) , and the remaining five formed the untreated control group . Serum sample s from two time points were used to measure HBV DNA levels and antiviral drug resistance . The LMV-treated women achieved a median HBV DNA reduction of 2.6-log10 IU/mL. Although end-of-treatment ( EOT ) HBV DNA in four ( 18 % ) LMV-treated women remained at > 10(7 ) IU/mL ( ± 0.5 log IU/mL ) , no mother-to-baby transmission was observed . In contrast , a baby from the untreated mother was HBsAg positive at 9 months postpartum . Four technologies were used for drug resistance testing . Only ultra-deep pyrosequencing ( UDPS ) was sufficiently sensitive to detect minor viral variants down to < 1 % . UDPS showed that LMV therapy result ed in increased viral quasispecies diversity and positive selection of HBV variants with reverse transcriptase amino acid substitutions at sites associated with primary LMV resistance ( rtM204I/V and rtA181 T ) in four ( 19 % ) women . These viral variants were detected mostly at low frequencies ( 0.63 - 5.92 % ) at EOT , but one LMV-treated mother had an rtA181 T variant that increased from 2.2 % pretherapy to 25.59 % at EOT . This mother was also infected with the vaccine escape variant ( sG145R ) , which was inhibited by LMV treatment . LMV therapy during late pregnancy only reduced maternal viraemia moderately , and drug-resistant viral variants emerged BACKGROUND The combination of one non-nucleoside reverse transcriptase inhibitor ( NNRTI ) with two nucleoside reverse transcriptase inhibitors is a vali date d first-line antiretroviral ( ARV ) therapy . The once-daily combination of lamivudine , tenofovirDF and nevirapine has not been evaluated in a clinical trial . METHODS R and omized , open-label , multicentre , non-inferiority trial comparing lamivudine , tenofovirDF and nevirapine once daily ( Group 2 ) with zidovudine/lamivudine and nevirapine twice daily ( Group 1 ) , in naive HIV-1-infected patients with a CD4 count < 350/mm(3 ) . We planned to enroll 250 patients . RESULTS As of May 2006 , 71 patients had been enrolled ( 35 in Group 1 and 36 in Group 2 ) and an unplanned interim analysis was done . The groups were comparable at baseline : median CD4 count was 195 and 191/mm(3 ) and median plasma viral load was 4.9 log(10 ) and 5.01 log(10 ) , respectively , in Groups 1 and 2 . Eight early non-responses ( 22.2 % ) were observed , all in Group 2 , while two later viral rebounds occurred . Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I ( n = 3 ) , K65R ( n = 6 ) , one or more NNRTI resistance mutations in all cases . At baseline , the nine Group 2 patients who failed had higher median plasma viral load ( 5.4 log(10 ) ) and lower median CD4 count ( 110/mm(3 ) ) than the other Group 2 patients ( 4.7 log(10 ) , P = 0.002 and 223/mm(3 ) , P = 0.004 ) . Nevirapine trough concentrations were not different between the two groups , nor between patients with full viral suppression or those who failed in Group 2 . Due to slow recruitment , and those results , the steering committee decided to stop the trial at 12 months . CONCLUSIONS In ARV-naive HIV-1-infected patients , the once-daily lamivudine , tenofovirDF and nevirapine regimen result ed in a high rate of early virological failures . The reasons for the failures remain unclear Hepatitis B immunoprophylaxis failure is linked to high maternal viraemia . There is limited North American data on hepatitis B outcomes in pregnancy . Pregnant hepatitis B carriers were enrolled January 2011-December 2014 and offered tenofovir in the 3rd trimester if hepatitis B virus (HBV)-DNA was > 7-log IU/mL. Outcomes were determined in treated vs untreated patients . In total , 161 women with 169 pregnancies ( one twin , 170 infants ; median age 32 years ) , 18 % ( 29/161 ) HBeAg+ and median HBV-DNA 2.51 log IU/mL ( IQR 1.66 - 3.65 ; range 0.8 - 8.1 ) were studied . 14.3 % ( 23/161 ) received tenofovir due to high viral load ( 16/23 , median 74 days , IQR 59 - 110 ) or due to liver disease ( 7/23 ) . In 10/16 treated due to high viraemia , with confirmed adherence , follow-up HBV-DNA showed a 5.49 log decline ( P = 0.003 ) . In treatment naïve mothers , median alanine aminotransferase ( ALT ) increased from 17 IU/L ( IQR 12 - 24 ) to 29 ( IQR 18 - 36 ) post-partum ( P = 1.5e-7 ) . In seven highly viraemic mothers who declined therapy ( HBV-DNA > 8-log IU/mL ) ; median ALT increased ~3X from baseline ( P < 0.01 ) . 26 % ( 44/169 ) had Caesarean section with no difference in treated vs untreated subjects . No tenofovir-treated mothers had renal dysfunction . Data were available on 167/170 infants ; in 50.8 % ( 85/167 ) who completed immunoprophylaxis , 98.8 % ( 84/85 , including 12 exposed to tenofovir in utero ) were HBV immune . One infant born to an HBeAg+ mother with HBV-DNA > 8-log IU/mL failed immunoprophylaxis . In this prospect i ve Canadian cohort study , most untreated mothers experienced mild HBV flares . Tenofovir in pregnancy is well tolerated and reduces viral load prior to parturition # # # # What you need to know What is the role of arthroscopic surgery in degenerative knee disease ? An expert panel produced these recommendations based on a linked systematic review triggered by a r and omised trial published in The BMJ in June 2016 , which found that , among patients with a degenerative medial meniscus tear , knee arthroscopy was no better than exercise therapy . The panel make a strong recommendation against arthroscopy for degenerative knee disease . Box 1 shows all of the articles and evidence linked in this Rapid Recommendation package . The infographic provides an overview of the absolute benefits and harms of arthroscopy in st and ard GRADE format . Table 2 below shows any evidence that has emerged since the publication of this article . # # # # Box 1 : Linked articles in this BMJ Rapid Recommendations BACKGROUND Data from r and omized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus ( HIV ) infection who have a CD4 + count of more than 350 cells per cubic millimeter . METHODS We r and omly assigned HIV-positive adults who had a CD4 + count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately ( immediate-initiation group ) or to defer it until the CD4 + count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome ( AIDS ) or another condition that dictated the use of antiretroviral therapy ( deferred-initiation group ) . The primary composite end point was any serious AIDS-related event , serious non-AIDS-related event , or death from any cause . RESULTS A total of 4685 patients were followed for a mean of 3.0 years . At study entry , the median HIV viral load was 12,759 copies per milliliter , and the median CD4 + count was 651 cells per cubic millimeter . On May 15 , 2015 , on the basis of an interim analysis , the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy . The primary end point occurred in 42 patients in the immediate-initiation group ( 1.8 % ; 0.60 events per 100 person-years ) , as compared with 96 patients in the deferred-initiation group ( 4.1 % ; 1.38 events per 100 person-years ) , for a hazard ratio of 0.43 ( 95 % confidence interval [ CI ] , 0.30 to 0.62 ; P<0.001 ) . Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 ( 95 % CI , 0.15 to 0.50 ; P<0.001 ) and 0.61 ( 95 % CI , 0.38 to 0.97 ; P=0.04 ) , respectively . More than two thirds of the primary end points ( 68 % ) occurred in patients with a CD4 + count of more than 500 cells per cubic millimeter . The risks of a grade 4 event were similar in the two groups , as were the risks of unscheduled hospital admissions . CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4 + count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4 + count had declined to 350 cells per cubic millimeter . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; START Clinical Trials.gov number , NCT00867048 . ) BACKGROUND R and omized-trial data on the risks and benefits of antiretroviral therapy ( ART ) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus ( HIV ) in HIV-infected pregnant women with high CD4 counts are lacking . METHODS We r and omly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum " tail " of tenofovir and emtricitabine ( zidovudine alone ) ; zidovudine , lamivudine , and lopinavir-ritonavir ( zidovudine-based ART ) ; or tenofovir , emtricitabine , and lopinavir-ritonavir ( tenofovir-based ART ) . The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety . RESULTS The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation ( interquartile range , 21 to 30 ) . The rate of transmission was significantly lower with ART than with zidovudine alone ( 0.5 % in the combined ART groups vs. 1.8 % ; difference , -1.3 percentage points ; repeated confidence interval , -2.1 to -0.4 ) . However , the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone ( 21.1 % vs. 17.3 % , P=0.008 ) , and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone ( 2.9 % vs. 0.8 % , P=0.03 ) . Adverse events did not differ significantly between the ART groups ( P>0.99 ) . A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone ( 23.0 % vs. 12.0 % , P<0.001 ) and was more frequent with tenofovir-based ART than with zidovudine alone ( 16.9 % vs. 8.9 % , P=0.004 ) ; preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone ( 20.5 % vs. 13.1 % , P<0.001 ) . Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks ( 6.0 % vs. 2.6 % , P=0.04 ) and early infant death ( 4.4 % vs. 0.6 % , P=0.001 ) , but there were no significant differences between tenofovir-based ART and zidovudine alone ( P=0.10 and P=0.43 ) . The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART . CONCLUSIONS Antenatal ART result ed in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes . ( Funded by the National Institutes of Health ; PROMISE Clinical Trials.gov numbers , NCT01061151 and NCT01253538 . ) The efficacy and safety of maternal tenofovir disoproxil fumarate ( TDF ) in reducing mother‐to‐infant hepatitis B virus ( HBV ) transmissions is not clearly understood . We conducted a prospect i ve , multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen – positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication ( control group , n = 56 , HBV DNA 8.22 ± 0.39 log10 IU/mL ) or TDF 300 mg daily ( TDF group , n = 62 , HBV DNA 8.18 ± 0.47 log10 IU/mL ) from 30‐32 weeks of gestation until 1 month postpartum . Primary outcome was infant HBsAg at 6 months old . At delivery , the TDF group had lower maternal HBV DNA levels ( 4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL , P < 0.0001 ) . Of the 121/123 newborns , the TDF group had lower rates of HBV DNA positivity at birth ( 6.15 % versus 31.48 % , P = 0.0003 ) and HBsAg positivity at 6 months old ( 1.54 % versus 10.71 % , P = 0.0481 ) . Multivariate analysis revealed that the TDF group had lower risk ( odds ratio = 0.10 , P = 0.0434 ) and amniocentesis was associated with higher risk ( odds ratio 6.82 , P = 0.0220 ) of infant HBsAg positivity . The TDF group had less incidence of maternal alanine aminotransferase ( ALT ) levels above two times the upper limit of normal for ≥3 months ( 3.23 % versus 14.29 % , P = 0.0455 ) , a lesser extent of postpartum elevations of ALT ( P = 0.007 ) , and a lower rate of ALT over five times the upper limit of normal ( 1.64 % versus 14.29 % , P = 0.0135 ) at 2 months postpartum . Maternal creatinine and creatinine kinase levels , rates of congenital anomaly , premature birth , and growth parameters in infants were comparable in both groups . At 12 months , one TDF‐group child newly developed HBsAg positivity , presumably due to postnatal infection and inefficient humoral responses to vaccines . Conclusions : Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations . ( Hepatology Background : Abacavir sulfate/lamivudine ( ABC/3TC ) and tenofovir DF/emtricitabine ( TDF/FTC ) are widely used nucleoside reverse transcriptase inhibitors for initial HIV-1 treatment . This is the first completed , r and omized clinical trial to directly compare the efficacy , safety , and tolerability of these agents , each in combination with lopinavir/ritonavir in antiretroviral-naive patients . Methods : Six hundred and eighty-eight antiretroviral-naive , HIV-1-infected patients were r and omized in this double-blind , placebo-matched , multicenter , noninferiority study to receive a once-daily regimen of either ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg , both with lopinavir/ritonavir 800 mg/200 mg . Primary endpoints were the proportion of patients with HIV-1 RNA below 50 copies/ml at week 48 ( missing = failure , switch included analysis ) and the proportion of patients experiencing adverse events over 96 weeks . Results : At week 48 , 68 % in the ABC/3TC group vs. 67 % in the TDF/FTC group achieved an HIV-1 RNA below 50 copies/ml ( intent-to-treat exposed missing = failure , 95 % confidence interval on the difference −6.63 to 7.40 , P = 0.913 ) , demonstrating the noninferiority of ABC/3TC to TDF/FTC at week 48 . Noninferiority of the two regimens was sustained at week 96 ( 60 % vs. 58 % , respectively , 95 % confidence interval −5.41 to 9.32 , P = 0.603 ) . In addition , efficacy of both regimens was similar in patients with baseline HIV-1 RNA ≥ 100 000 copies/ml or CD4 + cell counts below 50 cells/μl . Median CD4 + recovery ( ABC/3TC vs. TDF/FTC , cells/μl ) was + 250 vs. + 247 by week 96 . Premature study discontinuation due to adverse events occurred in 6 % of patients in both groups . Protocol -defined virologic failure occurred in 14 % of patients in both groups . Conclusion : Both ABC/3TC and TDF/FTC provided comparable antiviral efficacy , safety , and tolerability when each was combined with lopinavir/ritonavir in treatment-naive patients BACKGROUND & AIMS Perinatal transmission of hepatitis B virus still occurs despite immunoprophylaxis in approximately 9 % of children from highly viraemic mothers . Antiviral therapy in this setting has been suggested , however with limited evidence to direct agent choice . METHODS We conducted a multi-centre , prospect i ve , opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load ( > 7 log IU/ml ) ; lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate ( TDF ) from late 2010 . Outcomes of treated and untreated cohorts were compared . RESULTS 120 women with 130 pregnancies used TDF ( 58 ) , lamivudine ( 52 including four who switched due to TDF intolerance ) and no therapy ( 20 ) . 96 % were HBeAg positive , with baseline viral load mean 7.8 log IU/ml ( ±0.72 ) and ALT median 25 U/L ( 18.75 - 33 ) . Duration of antiviral theraphy before birth was mean 58 days ( ±19 ) TDF and 53 ( ±14 ) lamivudine . Viral load declined by 3.64 log IU/ml ( ±0.9 ) TDF and 2.81 log IU/ml ( ±1.33 ) lamivudine . Virologic failure ( birth viral load > 7 IU/ml ) occurred in 3 % and 18 % respectively . Congenital abnormality rate and neonatal growth centiles were similar across cohorts . Perinatal transmission reduced significantly to 2 % and 0 % in TDF and lamivudine cohorts , compared with 20 % in untreated . CONCLUSIONS TDF in this setting is safe , effective and more potent than lamivudine . Antiviral therapy did not adversely impact obstetric or infant parameters . More TDF intolerance occurred than expected . Perinatal transmission was significantly reduced in antiviral therapy cohorts |
2,173 | 26,553,731 | Conclusions The majority of comparative , prophylactic migraine RCTs do not include a placebo arm .
Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine-prophylactic agents . | Background The Clinical Trials Subcommittee of the International Headache Society ( IHS ) recommends that a placebo arm is included in comparative r and omised clinical trials ( RCTs ) of multiple prophylactic drugs due to the highly variable placebo response in migraine prophylaxis studies .
The use of placebo control in such trials has not been systematic ally assessed . | OBJECTIVE To investigate the effect of low-intensity acenocoumarol treatment ( target INR 1.5 to 2.0 ) on the frequency and severity of migraine attacks . BACKGROUND The positive effect of anticoagulation on migraine has been described in case reports and observational studies . METHODS We conducted a r and omized , open , crossover study in migraine patients . After a run-in period of 8 weeks , all patients received acenocoumarol or propranolol during a period of 12 weeks and , after a washout period of 2 weeks , propranolol or acenocoumarol during a second period of 12 weeks . RESULTS Nineteen patients fulfilling the criteria were included . In 12 patients with complete data collection , only one good responder could be noted . In the other patients , treatment with low-intensity acenocoumarol did not show improvement of migraine symptoms compared with the run-in period . Treatment with propranolol showed a trend towards improvement compared with the run-in period . No serious adverse events were observed . CONCLUSIONS Overall , low-intensity acenocoumarol treatment has no prophylactic effect in migraine patients OBJECTIVE This multi-center pilot study compared the efficacy of onabotulinumtoxinA with topiramate ( a Food and Drug Administration approved and widely accepted treatment for prevention of migraine ) in individuals with chronic migraine ( CM ) . METHODS A total of 59 subjects with CM were r and omly assigned to one of 2 groups : Group 1 ( n = 30 ) received topiramate plus placebo injections , Group 2 ( n = 29 ) received onabotulinumtoxinA injections plus placebo tablets . Subjects maintained daily headache diaries over a 4-week baseline period and a 12-week active study period . The primary endpoint was the Physician Global Assessment , which measured the treatment responder rate and indicated improvement in both groups over 12 weeks . Secondary endpoints , measured at weeks 4 and 12 , included headache days per month , migraine days , headache-free days , days on acute medication , severity of headache episodes , Migraine Impact & Disability Assessment , Headache Impact Test , effectiveness of and satisfaction with current treatment on the amount of medication needed , and the frequency and severity of migraine symptoms . At 12 weeks subjects were re-evaluated and tapered off oral study medications over a 2-week time period . Subjects not reporting a > 50 % reduction of headache frequency at 12 weeks were invited to participate in a 12-week open label extension study with onabotulinumtoxinA. Of these , 20 subjects , 9 from the Topiramate Group and 11 from the OnabotulinumtoxinA Group , volunteered for this extension from weeks 14 to 26 . RESULTS This study demonstrated positive benefit for both onabotulinumtoxinA and topiramate in subjects with CM . Overall , the results were statistically significant within groups but not between groups . By week 26 , subjects had a reduction of headache days per month compared with baseline . This was a significant within-group finding . CONCLUSION OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures The calcium-entry blocker flunarizine ( Sibelium ; Janssen ) was compared with the beta-adrenoreceptor-blocking agent propranolol in the prophylaxis of migraine . Fifty-eight patients were entered into a double-blind 4-month treatment trial . Patients in whom beta-blockers were contraindicated were excluded from the trial . At the end of the trial 28 patients had received 10 mg flunarizine at night during the study , 29 patients had received 60 mg propranolol 3 times a day and 1 patient was withdrawn . Both groups responded well ; and there was a 4-fold drop in frequency of attacks . There was no significant difference between the two groups in terms of patient profile , onset of response to therapy , final response to therapy , incidence of dropout from the trial or incidence of side-effects . Side-effects for flunarizine were weight gain ( 9 patients ) and tiredness ( 6 ) , and for propranolol sleep disturbances including nightmares ( 6 ) , tiredness ( 8) , mental changes ( e.g. irritability ) ( 3 ) and weight gain ( 4 ) . Both flunarizine and propranolol are useful drugs for migraine prophylaxis and can be used effectively as first-line drugs . The low incidence of generally mild side-effects with flunarizine may make it preferable to many of the agents at present in use for migraine prophylaxis Acute treatment of menstrual migraine ( MM ) attacks is often incomplete and unsatisfactory , and perimenstrual prophylaxis with triptans , oestrogen supplementation or naproxen sodium may be needed for decreasing frequency and severity of the attack . In this pilot , open-label , non-r and omised , parallel group study we evaluated , in 38 women with a history of MM , the efficacy of frovatriptan ( n=14 ) 2.5 mg per os or transdermal oestrogens ( n=10 ) 25 μg or naproxen sodium ( n=14 ) 500 mg per os once-daily for the short-term prevention of MM . All treatments were administered in the morning for 6 days , beginning 2 days before the expected onset of menstrual headache . All women were asked to fill in a diary card , in the absence of ( baseline ) and under treatment , in order to score headache severity . All women reported at least one episode of MM at baseline . During treatment all patients taking transdermal oestrogens or naproxen sodium and 13 out of the 14 patients ( 93 % ) taking frovatriptan had at least one migraine attack ( p=0.424 ) . Daily incidence of migraine was significantly ( p=0.045 ) lower under frovatriptan than under transdermal oestrogens or NS . At baseline , the overall median score of headache severity was 4.6 , 4.2 and 4.3 in the group subsequently treated with frovatriptan , transdermal oestrogens and naproxen sodium , respectively ( p=0.819 ) . During treatment the median score was significantly lower under frovatriptan ( 2.5 ) than under transdermal oestrogens ( 3.0 ) and naproxen sodium ( 3.9 , p=0.049 ) . This was evident also for each single day of observation ( p=0.016 ) . Among treatments differences were particularly evident for the subgroup of patients with true MM ( n=22 ) and for frovatriptan vs. naproxen sodium . This study suggests that short-term prophylaxis of MM with frovatriptan may be more effective than that based on transdermal oestrogens or naproxen sodium AIM Topiramate is a small molecule widely used for the treatment of epilepsy , migraine , bipolar disorders and alcoholism , and its availability as a generic formulation could significantly reduce the National Health Service expenditure . A generic formulation , available in Italy under the trademark Sincronil , recently showed superimposable blood levels , after oral administration to healthy volunteers , with the reference formulation . In the present study we report the results of an open label , parallel group , r and omized , controlled study performed to evaluate the efficacy , tolerability and impact on disability of two different formulations of topiramate ( Sincronil and Topamax ) in patients with migraine without aura . METHODS Sixty patients aged between 18 and 65 years , suffering from migraine without aura with an attack frequency of 3 - 15 attacks/month were enrolled and received , after a titration phase lasting 20 days , r and omly either Sincronil or Topamax at the dose of 25 mg twice daily for 3 months . RESULTS Fifteen out of the 30 patients who were administered Sincronil reported an improvement in the clinical condition , with a decrease in the frequency of attacks at the 3rd month of treatment higher than 50 % with respect to the run-in period , 9 reported their clinical condition as being substantially unchanged and 6 reported that they had suspended the treatment within the first 4 weeks of therapy due to side effects . Among the 24 patients who continued treatment up to the 3rd month , the frequency of attacks during the 3rd month of treatment was significantly decreased from 7 ± 3.6 to 3.7 ± 3.7 ( P<0.0001 ) , migraine severity was reduced from 2.5 ± 0.5 to 1.7 ± 0.7 ( P<0.0005 ) and the MIDAS score was reduced from 14.3 ± 4.9 to 8.6 ± 5.5 ( P<0.0001 ) . Sixteen out of the 30 patients who were administered Topamax reported an improvement in the clinical condition with a reduction in the attack frequency at the 3rd month of treatment higher than 50 % with respect to the run-in period , 10 reported a substantially unchanged clinical condition and 4 stopped the treatment within the first weeks due to side effects . Among the 26 patients who continued treatment up to the 3rd month , headache frequency during the 3rd month of treatment was significantly reduced , from 7.3 ± 2.6 to 3.5 ± 2.7 ( P<0.0001 ) , migraine severity decreased from 2.4 ± 0.6 to 1.6 ± 0.8 ( P<0.0005 ) and the MIDAS score from 14.1 ± 4.2 to 6.8 ± 4.8 ( P<0.0001 ) . CONCLUSION In conclusion , in this study Topamax ( reference product ) and Sincronil ( generic formulation ) have proven therapeutically equivalent and both products were well tolerated The clinical efficacy of flunarizine and of propranolol for the prevention of migraine attacks was assessed in a multicenter double-blind study lasting four months which was preceded by a single-blind placebo period of one month . For both drugs , more than half of the patients judged the effect to be good or very good . When considering the patients ' daily logs , both drugs produced a significant reduction of the number of attacks . Propranolol furthermore significantly reduced the severity of attacks and the number of analgesics used during the attacks . In both groups no severe side effects were observed Migraine can not be cured and the aim , shared with the patient , is to minimise the impact of the illness on the patient 's life and lifestyle . The aim of prophylaxis is to reduce the number of migraine attacks . Prophylaxis should be considered when appropriately used acute management gives inadequate control of symptoms . The efficacy and safety of topiramate 50 mg/d and thioctic acid ( α-lipoic acid ) 300 mg/d either as monotherapy or in combination were investigated as migraine prophylactic agents . Forty secondary school migraineur girls were enrolled in the study . The study was conducted in two phases , a prospect i ve baseline phase and 1-month treatment phase . Combined topiramate/thioctic acid therapy was more effective than either topiramate or thioctic acid monotherapy as a migraine-preventive treatment . Combined topiramate/thioctic acid therapy decreased the mean monthly migraine frequency from 5.86 ± 1.2 to 2.6 ± 0.98 ( p ⩽ 0.05 ) , topiramate ( 50 mg/d ) from 5.71 ± 1.4 to 4.75 ± 1.5 and thioctic acid ( 300 mg/d ) from 5.68 ± 1.6 to 5.22 ± 1.8 . Reduction in mean monthly migraine days was also significantly greater in the group receiving combined topiramate/thioctic acid ( from 12.32 ± 1.85 to 5.74 ± 1.1 ) compared to those receiving either topiramate 50 mg/d ( from 12.7 ± 1.34 to 11.85 ± 1.35 ) or thioctic acid 300 mg/d ( from 12.5 ± 1.72 to 11.65 ± 1.44 ) . The responder rate ( % of patients showing ⩾50 % reduction in monthly migraine frequency ) was 85 % in patients receiving combined topiramate/thioctic acid therapy compared to 30 % and 20 % in patients receiving either topiramate or thioctic acid , respectively . The incidence of adverse events was higher in patients receiving topiramate ( 50 mg/d ) monotherapy . The most common adverse events were nausea , fatigue , paraesthesia and taste perversion . We conclude that combined topiramate/thioctic acid therapy is more effective and better tolerated than topiramate monotherapy . The combination has lower monthly medication costs compared to the traditionally used topiramate 100 mg monotherapy In patients with migraine with or without aura the prophylactic effect of amitriptyline ( AMT ) and venlafaxine ( VLF ) was compared in a r and omized double-blind crossover study . Intolerable side effects result ed in drop out of five patients on AMT ( due to hypersomnia , difficulty in concentration and orthostatic hypotension ) and one patient on VLF ( because of nausea and vomiting ) . Following the run-in period the patients ( n = 52 ) were r and omly treated with one of the study medications for 12 weeks . After a wash-out period lasting 4 weeks the patients were treated with the other drug for further 12 weeks . Both drugs had significant beneficial effect on pain parameters . Total number of side effects of VLF was low when compared with the side effect profile of AMT . In conclusion , it is suggested that VLF may be considered for the prophylaxis of migraine because of its low and /or tolerable side effect properties OBJECTIVE To evaluate the efficacy of oral treatment with nebivolol and metoprolol in the prophylaxis of migraine attacks . BACKGROUND Beta-blockers such as propranolol and metoprolol are known to be effective in preventing migraine attacks . Following earlier observations of successful use of nebivolol in a few hypertensive patients with concomitant migraine , we conducted a prospect i ve study to ascertain whether nebivolol would be effective and better tolerated , in a method ologically strict , r and omized and double-blind setting . DESIGN AND METHODS R and omized , double-blind study in 30 patients with confirmed migraine diagnosis , a minimum 1-year history , onset prior to 50 years of age , written records of attacks for the previous 3 months , and minimum 2 attacks per month . Primary endpoint was frequency of attacks ( prevention of migraine attacks ) in the final 4 weeks of a 14-week treatment on full dose of metoprolol and nebivolol . Secondary endpoints were time to therapeutic effect , duration of attacks , intensity of headache , consumption of analgesics , evaluation of accompanying symptoms , migraine disability assessment , clinical global impression , quality of life , and responder rates . The statistical analysis was prospect ively planned and conducted for all r and omized patients . RESULTS Both metoprolol and nebivolol where similarly effective regarding the main endpoint ( prevention of migraine attacks ) as well as the secondary ones , and both had a fast onset of action , typically within 4 weeks from starting therapy , with responder rates increasing relatively little over time after the first 4 weeks . Use of acute pain medication decreased on both drugs , as well as accompanying symptoms . Both patients ' and physicians ' evaluations of disability and disease status were similarly favorable to the 2 treatments . Regarding safety , nebivolol was considerably better tolerated than metoprolol in terms of all reported events , treatment-related events , and event severity . CONCLUSIONS Our results suggest that nebivolol is as effective as metoprolol in the prophylaxis of migraine attacks , with the advantages of being better tolerated and not requiring up-titration to achieve therapeutic levels . Further and larger trials should be conducted on nebivolol in the prevention of migraine attacks as it may provide an improvement in current migraine prophylaxis with beta-blockers OBJECTIVE To compare the efficacy and safety of botulinum toxin type A ( BoNTA ; BOTOX : Allergan , Inc. ) and divalproex sodium ( DVPX ; DEPAKOTE : Abbott Laboratories ) as prophylaxis in reducing disability and impact associated with migraine . BACKGROUND There is a need for effective , well-tolerated prophylactic treatment of migraine . DESIGN / METHODS This was a r and omized , double-blind , single-center prospect i ve study . Fifty-nine patients received either BoNTA 100 U/placebo-DVPX bid or placebo-BoNTA/DVPX 250 mg bid . BoNTA/placebo injections were given at Day 0 and at Month 3 . Patients were evaluated at Months 1 , 3 , 6 , and 9 . RESULTS Both treatments showed significant improvements in migraine disability scores and reductions in headache days and headache index . A trend to decreased headache severity was observed with BoNTA . A greater percentage of DVPX patients reported adverse events possibly related to treatment ( DVPX 75.8 % vs BoNTA 50 % , P = .04 ) and discontinued because of adverse events ( DVPX 27.6 % vs BoNTA 3.3 % , P = .012 ) . CONCLUSIONS Both BoNTA and DVPX significantly reduced disability associated with migraine ; BoNTA had a favorable tolerability profile compared with DVPX This study was design ed to compare flunarizine , a cerebro-specific calcium channel antagonist , and propranolol in the prophylaxis of migraine with or without aura . Following a 1 month single-blind placebo baseline period , 94 patients were equitably r and omised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months . Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months . Neither treatment affected the severity nor duration of migraines . Overall , 67 % of flunarizine patients and 51 % of propranolol patients responded positively . Propranolol significantly reduced blood pressure and heart rate ; flunarizine had no effect on cardiovascular function . Weight gain was noted with both treatments . Flunarizine is at least as effective as propranolol in the prophylactic treatment of migraine and may have a better safety profile OBJECTIVE To compare the efficacy and safety of topiramate with gabapentin in the prophylaxis of migraine patients . METHODS A 12-week r and omised open label control trial was conducted at the Department of Pharmacology and Therapeutics , Basic Medical Sciences Institute , Jinnah Postgraduate Medical Centre ( JPMC ) , Karachi from January to March 2011 involving 80 out patients who had a history of migraine . The sample was divided into two equal groups . Primary efficacy measure was changed into mean monthly migraine frequency . Secondary efficacy measure included reduction in severity and average duration of an attack . Chi square test and paired t-test were used to analyse the data through SPSS 15 . RESULT Reduction in mean monthly migraine frequency ( 10.67 + /- 4.25 to 1.82 + /- 2.02 ) in the topiramate group was significantly greater compared with ( 11.97 + /- 4.452 to 2.73 + /- 2.59 ) that in the gabapentin group ( p < 0.001 ) . Reduction in severity from 6.60 + /- 2.122 to 1.03 + /- 0.92 in the topiramate group was also significantly greater compared with 6.93 + /- 1.90 to 1.18 + /- 1.01 in the gabapentin group ( p < 0.001 ) . Reduction in the average duration of attacks from 25.77 + /- 22.32 hours to 1.05 + /- 1.06 hours in the topiramate group was significantly greater compared with 22.20 + /- 20.72 to 1.08 + /- 1.40 hours in the gabapentin group ( p < 0.001 ) . Weight loss and numbness were common adverse effects in the topiramate group . Dizziness , weight gain and somnolence were reported in the gabapentin group . CONCLUSION Gabapentin appeared well tolerated in 30 ( 75 % ) patients compared to topiramate in 23(57.5 % ) patients . Both drugs were equally effective in migraine prophylaxis Background : Topiramate is an antiepileptic drug that has been approved for migraine prophylaxis . Despite appropriate efficacy for migraine prophylaxis , some patients can not tolerate its adverse effects . The aim of this study was to compare the efficacy of zonisamide , another antiepileptic drug , with topiramate in decreasing the frequency and severity of migraine attacks to determine whether it could be used as an alternative for noncompliant patients to topiramate . Methods : Eighty patients , recruited from referred migraineurs to our neurology clinic , who met the diagnosis and inclusion criteria were allocated r and omly to group A ( 50-mg/d zonisamide , gradually titrated up to 200 mg/d ) and group B ( 25-mg/d topiramate , gradually titrated up to 100 mg/d ) . Each patient was followed for 12 weeks and was assessed at entrance , in the fourth week and twelfth week for frequency of attacks , headache severity , need for acute medication , migraine disability assessment score , and adverse effects . A P < 0.05 was considered as the level of significant difference in all tests . Results : Both drugs caused a significant decrease in frequency , severity , need for acute medication in migraine attacks , and migraine disability assessment score ( P < 0.05 ) . Except headache severity that was reduced significantly better by zonisamide ( P < 0.008 ) , there were no significant difference between the 2 groups in other items . Except for 2 cases of intolerable paresthesia , both drugs were tolerated well during the study . Conclusion : Our results indicated that zonisamide is as effective as topiramate in migraine prophylaxis and can be considered as an alternative treatment when topiramate is not tolerated well Objective The objective of this article is to see whether the effect of c and esartan for migraine prevention , shown in one previous study , could be confirmed in a new study , and if so , whether the effect was comparable to that of propranolol ( non-inferiority analysis ) , and whether adverse events were different . Methods In a r and omised , triple-blind , double cross-over study , 72 adult patients with episodic or chronic migraine went through three 12-week treatment periods on either c and esartan 16 mg , propranolol slow-release 160 mg , or placebo . The main outcome measures were days with migraine headache per four weeks ( primary outcome ) , days with headache , hours with headache , proportion of responders ( > 50 % reduction of migraine days from baseline ) , and adverse events . Results In the modified intention-to treat- analysis , c and esartan and propranolol were both superior to placebo : 2.95 ( 95 % confidence interval : 2.35–3.55 % ) and 2.91 ( 2.36–3.45 % ) , versus 3.53 ( 2.98–4.08 % ) for migraine days per month ( p = 0.02 for both comparisons , Wilcoxon 's paired signed rank test , blinded statistical analysis ) . C and esartan was non-inferior to propranolol ( and vice versa ) . The proportion of responders was significantly higher on c and esartan ( 43 % ) and propranolol ( 40 % ) than on placebo ( 23 % ) ( p = 0.025 and < 0.050 , respectively ) . There were more adverse events on c and esartan ( n = 133 % ) and propranolol ( n = 143 % ) than on placebo ( n = 90 % ) , and the adverse event profiles of the active substances differed somewhat . Conclusion It is confirmed that c and esartan 16 mg is effective for migraine prevention , with an effect size similar to propranolol 160 mg , and with somewhat different adverse events . Trial registration : EUDRACT ( 2008 - 002312 - 7 ) , Clinical Trials.gov ( NCT00884663 ) OBJECTIVE To compare the effects of botulinum toxin type A with those of amitriptyline on the treatment of chronic daily migraines . METHODS Chronic migraine sufferers were r and omized into two groups and treated with 25 or 50mg/day of amitriptyline or 250U of botulinum toxin type A. A reduction of at least 50 % in the number of pain episodes , in the intensity of pain , and in the number of drug doses for pain and reports of improvement by the patient or by the examiner were the main endpoints . RESULTS Seventy-two subjects were enrolled in the study . A reduction of at least 50 % in the number of days of pain was recorded in 67.8 % of the patients in the BTX-A group and 72 % ( n=23 ) of the patients in the AM group ( p=0.78 ; RR=0.94 ; CI=0.11 - 8 ) . The reduction in the intensity of pain , as assessed using the visual analogical scale , was 50 % in the BXT-A group and 55.6 % in the AM group ( p=0.79 ; RR=1.11 ; CI=0.32 - 3.8 ) . The reduction in the number of pain drug doses was 77 % for the toxin group and 71 % for the amitriptyline group ( p=0.76 ; RR=0.92 ; CI=0.45 - 1.88 ) . CONCLUSIONS Botulinum toxin type A was as effective as amitriptyline for the prophylactic treatment of chronic daily migraines Within recent years a variety of agents have been employed for the symptomatic and prophylactic treatment of the migraine syndrome . The responses to two such agents , ergot derivatives and methysergide , have often been so striking as to have achieved the stature of diagnostic criteria . Despite this fact , a number of migraine sufferers remain without effective therapy because either they are not benefited by these drugs or they can not risk or tolerate the side effects produced by them . Recently , Rabkin et aL , l Wykes , z and Bekes et a13 independently noted seemingly fortuitous headache improvement in three patients with migraine treated for cardiovascular disease with propranolol , a beta-adrenergic receptor blocker . These observations coupled with our experimental results of propranolol 's effects on cerebral blood flow and metabolism * prompted a controlled study on the efficacy of this substance as a modifier of the migraine syndrome This intervention study conducted in the Neurology outpatient Department of Mymensingh Medical College Hospital ( MMCH ) from January 2006 to December 2007 to compare efficacy of amitriptyline , pizotifen and propranolol in the prophylaxis of migraine . Ninety cases were selected following certain inclusion and exclusion criteria . Result showed that the differences in duration , frequency and severity of attack were reduced in all groups but the differences among the groups were not significant ( p>0.05 ) . However , compared with amitriptyline and pizotifen , the propranolol group needed tablet paracetamol as abortive therapy less frequently which was statistically significant ( p<0.05 ) . All the drugs were well tolerated with minimum adverse effects OBJECTIVE The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache . METHODS This was a 26-week , multicenter , r and omized , double-blind , double-dummy , parallel-group noninferiority study . Adults with 3 to 12 migraines per month were r and omized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline , subsequently titrated to a maximum of 100 mg/d ( or the maximum tolerated dose ) . The primary efficacy outcome was the change from prospect i ve baseline in the mean monthly number of migraine episodes . Secondary efficacy variables included changes from the prospect i ve baseline phase to the end of the double-blind phase in the mean monthly ( 28-day ) rate of days with migraine , mean monthly rate of days with headache ( migraine and nonmigraine ) , mean monthly rate of acute abortive medication use , mean monthly migraine duration , and mean monthly migraine severity . Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms ( photophobia , phonophobia , and nausea ) , change in the mean monthly frequency f migraine-associated vomiting , and response rates ( based on monthly migraine days and total headache days ) . The Migraine-Specific Quality of Life Question naire ( MSQ ) and the Weight Satisfaction Scale Question naire , which measures subjective satisfaction with current weight , were administered . Treatment-emergent adverse events ( TEAEs ) were monitored through the end of double-blind treatment . RESULTS The intent-to-treat population included 331 subjects ( 172 topiramate , 159 amitriptyline ; 84.9 % female ; 84.6 % white ; mean [ SD ] age , 38.8 [ 11.0 ] years ; mean weight , 77.1 [ 20.1 ] kg ) who provided at least 1 efficacy assessment . The least squares mean ( LSM ) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups ( -2.6 and -2.7 , respectively ; 95 % CI , -0.6 to 0.7 ) . There were no significant differences between treatment groups in any of the prespecified secondary outcome measures . Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline ( LSM change : -0.33 vs -0.19 ; 95 % CI , -0.3 to 0.0 ; P = 0.040 ) and in the role function-restrictive , role function-preventive , and emotional function domains of the MSQ ( P = 0.012 , P = 0.014 , and P = 0.029 , respectively ) . Subjects receiving topiramate had a mean weight loss of 2.4 kg , compared with a mean weight gain of 2.4 kg in subjects receiving amitriptyline . Subjects in the topiramate group reported an overall improvement from baseline in weight satisfaction , whereas the amitriptyline group reported an overall deterioration in weight satisfaction ( P < 0.001 , topiramate vs amitriptyline ) . TEAEs of mild or moderate severity were reported in 118 subjects ( 66.7 % ) in the topiramate group and 112 subjects ( 66.3 % ) in the amitriptyline group . Among the most common TEAEs ( reported in + /-5 % of subjects during the double-blind phase ) in the topiramate group were paresthesia ( 29.9 % ) , fatigue ( 16.9 % ) , somnolence ( 11.9 % ) , hypoesthesia ( 10.7 % ) , and nausea ( 10.2 % ) . The most commonly reported TEAEs in the amitriptyline group were dry mouth ( 35.5 % ) , fatigue ( 24.3 % ) , somnolence ( 17.8 % ) , weight increase ( 13.6 % ) , dizziness ( 10.7 % ) , and sinusitis ( 10.7 % ) . CONCLUSIONS In this noninferiority study , topiramate was at least as effective as amitriptyline in terms of reducing the rate of mean monthly migraine episodes and all prespecified secondary efficacy end points . Topiramate was associated with improvement in some quality -of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction OBJECTIVE To assess the efficacy and safety of topiramate and lamotrigine for prophylaxis in patients with frequent migraine as compared to each other and to placebo . METHODS Sixty patients with frequent migraine ( more than 4 attacks per month ) from the headache clinic at a tertiary referral centre in India were r and omized to receive 50 mg topiramate/lamotrigine or matching placebo for 1 month each in 2 divided doses in 4 phases in a crossover manner with a washout period of 7 days in between . Primary efficacy measure was responder rate ( 50 % decrease in mean migraine frequency/intensity ) . Secondary efficacy measures included reduction in mean monthly frequency , intensity , duration , rescue medication use , migraine associated symptoms , and adverse events . STATISTICAL ANALYSIS Analysis was on intention to treat basis . Data were analyzed as correlated data . Generalized estimation equation was used to compute overall mean st and ard deviation and 95 % confidence intervals for each of the outcome variables . Bonferroni 's correction done for multiple comparisons . P value of < .017 was taken as significant . RESULTS Fifty-seven patients comprised the intent-to-treat population . Four patients withdrew from the study at various phases , none because of the side effects . Responder rate for frequency was significantly higher for topiramate versus placebo ( 63 % vs 30 % , P < .001 ) , and versus lamotrigine ( 63 % vs 46 % , P = .02 ) . For intensity of headache also a responder rate of topiramate versus placebo ( 50 % vs 10 % , P < .001 ) , and versus lamotrigine ( 50 % vs 41 % , P = .01 ) was observed . Topiramate showed statistically significant benefits ( P < .017 ) in most of the secondary efficacy measures while lamotrigine was beneficial for reduction in headache frequency , and migraine associated symptoms . Adverse events were similar . CONCLUSION Low-dose topiramate is efficacious in migraine prophylaxis as compared to both placebo and lamotrigine . Lamotrigine in low doses might be beneficial for headache frequency ; however , longer trials are required to establish its efficacy on the intensity and frequency of migraine OBJECTIVE To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin , magnesium , and feverfew . BACKGROUND Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results , and there has been only a single placebo-controlled trial of riboflavin . DESIGN / METHODS R and omized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg , magnesium 300 mg , and feverfew 100 mg . The placebo contained 25 mg riboflavin . The study included a 1-month run-in phase and 3-month trial . The protocol allowed for 120 patients to be r and omized , with a preplanned interim analysis of the data after 48 patients had completed the trial . RESULTS Forty-nine patients completed the 3-month trial . For the primary outcome measure , a 50 % or greater reduction in migraines , there was no difference between active and " placebo " groups , achieved by 10 ( 42 % ) and 11 ( 44 % ) , respectively ( P=.87 ) . Similarly , there was no significant difference in secondary outcome measures , for active versus placebo groups , respectively : 50 % or greater reduction in migraine days ( 33 % and 40 % , P=.63 ) ; or change in mean number of migraines , migraine days , migraine index , or triptan doses . Compared to baseline , however , both groups showed a significant reduction in number of migraines , migraine days , and migraine index . This effect exceeds that reported for placebo agents in previous migraine trials . CONCLUSION Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg , magnesium 300 mg , and feverfew 100 mg . The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis , and suggests that riboflavin 25 mg may be an active comparator . There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis Objectives : The aim of this study was to compare the efficacy of sodium valproate and topiramate in treating chronic migraine . Methods : Forty-nine patients with chronic migraine were r and omly assigned to 1 of 2 groups of treatment : 750 mg/day valproate or 75 mg/day topiramate . Efficacy variables were number of days with headache over a 30-day period and changes in Migraine Disability Assessment ( MIDAS ) scores at 3 months . Results : At baseline the 2 groups had similar numbers of days with headache and mean MIDAS scores . At the end of the treatment period , a significant reduction in 30-day headache frequency with respect to baseline ( P < 0.00001 ) and a significant reduction in MIDAS scores ( P < 0.00001 ) were recorded in both groups . There were no significant differences in beneficial effects between the 2 drugs . Discussion : Valproate and topiramate seem to be able to manage successfully chronic migraine without substantial differences in efficacy and tolerability . This affords clear practical advantages-in the event of failure of or intolerance for one treatment , the patient may be switched to the other There is evidence that some antidepressant drugs are beneficial in the prophylaxis of migraine . Previous reports have shown that migraine patients may respond to various antidepressant agents used for prophylactic therapy . The main purpose of this study was to compare the efficacy of antidepressants from 2 different groups ( venlafaxine vs escitalopram ) on people who had migraine headache without depression or anxiety . In this prospect i ve study , we evaluated the headache diaries of 93 patients who were being treated with venlafaxine ( n = 35 ) and escitalopram ( n = 58 ) . At the end of the 3-month period , patients were reassessed , and those with marked differences in attack frequency , duration , intensity ( with visual analog scales ) , lost work-day equivalent index , and migraine disability assessment question naire were compared . There was a clear reduction in headache frequency ( P < 0.0001 ) , duration ( P < 0.0001 ) , and severity ( P < 0.0001 ) in the venlafaxine group . In addition , there was a significant improvement in daily work performance during headaches ( P < 0.0001 ) . In the escitalopram group , monthly headache frequency ( P < 0.026 ) , duration ( P < 0.002 ) , and intensity ( P < 0.027 ) all decreased significantly , although not to the same extent as with venlafaxine . After the third month of venlafaxine and escitalopram treatment , most of the patients ( 82.8 % vs 96.5 % ) were seen to have moved to the minimal or infrequent migraine disability assessment group . According to our findings , venlafaxine and escitalopram are both effective in the prophylaxis of migraine headache without depression and anxiety . This effect was independent of mood disorder . Escitalopram should be the first choice because of its fewer side effects , but venlafaxine may be used if escitalopram is found to be insufficient OBJECTIVES The primary objective of this guideline is to assist the practitioner in choosing an appropriate prophylactic medication for an individual with migraine , based on current evidence in the medical literature and expert consensus . This guideline is focused on patients with episodic migraine ( headache on ≤ 14 days a month ) . METHODS Through a comprehensive search strategy , r and omized , double blind , controlled trials of drug treatments for migraine prophylaxis and relevant Cochrane review s were identified . Studies were grade d according to criteria developed by the US Preventive Services Task Force . Recommendations were grade d according to the principles of the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group . In addition , a general literature review and expert consensus were used for aspects of prophylactic therapy for which r and omized controlled trials are not available . RESULTS Prophylactic drug choice should be based on evidence for efficacy , side-effect profile , migraine clinical features , and co-existing disorders . Based on our review , 11 prophylactic drugs received a strong recommendation for use ( topiramate , propranolol , nadolol , metoprolol , amitriptyline , gabapentin , c and esartan , butterbur , riboflavin , coenzyme Q10 , and magnesium citrate ) and 6 received a weak recommendation ( divalproex sodium , flunarizine , pizotifen , venlafaxine , verapamil , and lisinopril ) . Quality of evidence for different medications varied from high to low . Prophylactic treatment strategies were developed to assist the practitioner in selecting a prophylactic drug for specific clinical situations . These strategies included : first time strategies for patients who have not had prophylaxis before ( a beta-blocker and a tricyclic strategy ) , low side effect strategies ( including both drug and herbal/vitamin/mineral strategies ) , a strategy for patients with high body mass index , strategies for patients with co-existent hypertension or with co-existent depression and /or anxiety , and additional monotherapy drug strategies for patients who have failed previous prophylactic trials . Further strategies included a refractory migraine strategy and strategies for prophylaxis during pregnancy and lactation . CONCLUSIONS There is good evidence from r and omized controlled trials for use of a number of different prophylactic medications in patients with migraine . Medication choice for an individual patient requires careful consideration of patient clinical features OBJECTIVE Effectiveness of antidepressants and antiepileptic drugs has already been demonstrated for migraine prophylaxis as monotherapy . In the present study , the efficacy and tolerability of amitriptyline and topiramate combination is examined in the prevention of migraine attacks , in comparison to the monotherapy of each drug . METHODS A total of 73 patients with migraine headache with or without aura are included in this single-center , double-blind , r and omized , and controlled trial . Patients were assigned to receive topiramate alone , amitriptyline alone or a combination of these drugs . Frequency , duration and severity of migraine attacks , accompanied symptoms , depressive state , consumption of medications , side effects and patient satisfaction were evaluated . RESULTS All treatments result ed in significant improvements in all efficacy measures ( p<0.001 for all comparisons ) . However , patients receiving combination treatment had higher patient satisfaction compared with other groups both at 8 and 12 weeks ( p=0.006 and p<0.001 , respectively ) . Patients receiving amitriptyline and combination treatments had better depression scores compared with the topiramate group . Combination group had fewer side effects with a less amount of amitriptyline consumption . CONCLUSION Amitriptyline and topiramate combination may be beneficial for patients with migraine and comorbid depression , particularly in terms of side effects and associated displeasure due to monotherapy BACKGROUND Topiramate and sodium valporate are anticonvulsants , demonstrated to be effective as monotherapy for migraine prevention in placebo-controlled trials . OBJECTIVES To compare the relative efficacy of topiramate and sodium valporate in the prevention of migraine . PATIENTS AND METHODS A 24-week , r and omized , double-blind , crossover , clinical trial was conducted from October 2003 to September 2004 . A total of 64 patients with migraine headache , aged 14 to 57 years , were r and omly allocated to the 2 treatment groups . The first group received topiramate ( 25 mg daily increment over 1 week to 50 mg ) for a total of 2 months . The second group received sodium valporate ( 200 mg daily increment over 1 week to 400 mg ) for 2 months . Response to treatment was assessed at 0 , 1 , 8 , 16 , and 24 weeks after start of therapy . RESULTS Topiramate appeared to be equivalent in efficacy and safety to sodium valporate . A significant decrease in duration , monthly frequency , and intensity of headache occurred in both groups . Of the 32 patients treated with sodium valporate , the mean st and ard deviation ( SD ) of monthly migraine frequency decreased from 5.4 ( 2.5 ) to 4.0 ( 2.8 ) episode per month , headache intensity from 7.7 ( 1.2 ) to 5.8 ( 1.7 ) by visual analog scale ( VAS ) , and headache duration from 21.3 ( 14.6 ) to 12.3 ( 10.7 ) hours ( P < .001 ) . Correspondingly , in the 32 patients treated with topiramate , the mean SD of monthly headache frequency decreased from 5.4 ( 2.0 ) to 3.2 ( 1.9 ) per month , headache intensity from 6.9 ( 1.2 ) to 3.7 ( 1.3 ) , and headache duration from 17.3 ( 8.4 ) to 3.9 ( 2.7 ) hours ( P < .001 ) . CONCLUSION This study demonstrates that treatment with topiramate and sodium valporate both significantly reduce migraine headache . This effect of topiramate and sodium valporate has previously been shown to reduce migraine headache , and we postulate that treatment with topiramate and sodium valporate may have a similar benefit OBJECTIVES To compare the efficacy and tolerability of the subcutaneous administration of histamine and botulinum toxin type A ( BoNTA ) in migraine prophylaxis . BACKGROUND Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology . METHODS One hundred patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine ( 1 - 10 ng twice a week ) n = 50 , compared with administration of 50 U of BoNTA ( one injection cycle ) n = 50 . RESULTS The data collected during the 4th week of treatment revealed a significant decrease in all parameters studied , in histamine and BoNTA ( P < 0.001 ) . After 4 weeks of treatment , but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy . CONCLUSIONS This r and omized study demonstrated that both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis . Low doses of histamine applied subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and lay the clinical and pharmacological groundwork for the use of H3 agonist in migraine prophylaxis In the course of a 16 weeks ' interval treatment of migraine in connection with two multicenter double-blind studies , flunarizine was compared with propranolol in patients suffering predominantly from “ classical migraine ” . Eighty-seven patients from 12 outpatient departments were admitted to the first study , while 434 patients from 99 medical practice s participated in the second study . After each month of treatment , the patients were clinical ly evaluated , and the number , duration , and severity of attacks were documented . Concerning the frequency and intensity of attacks , additional analgesics consumption and overall evaluation , both drugs proved to be highly effective in the practice as well as in the hospital study . The percentage and severity of side-effects were comparable in the two treatment groups . Summarizing , it may be stated that the studies proved the efficacy of flunarizine to be rather similar to that of propranolol in the prophylactic treatment of migraine |
2,174 | 27,267,490 | Conclusions The diversity of the US population is represented in a majority of cancer-related PtDA RCTs , but fewer studies have tailored PtDAs to address the multiple social disadvantages that may impact patients ’ participation in SDM . | Background Shared decision-making ( SDM ) is considered a key component of high quality cancer care and may be supported by patient decision aids ( PtDAs ) .
Many patients , however , face multiple social disadvantages that may influence their ability to fully participate in SDM or to use PtDAs ; additionally , these social disadvantages are among the determinants of health associated with greater cancer risk , unwarranted variations in care and worse outcomes . | Background Professional societies recommend shared decision making ( SDM ) for prostate cancer screening , however , most efforts have promoted informed rather than shared decision making . The objective of this study is to 1 ) examine the effects of a prostate cancer screening intervention to promote SDM and 2 ) determine whether framing prostate information in the context of other clearly beneficial men ’s health services affects decisions . Methods We conducted two separate r and omized controlled trials of the same prostate cancer intervention ( with or without additional information on more clearly beneficial men ’s health services ) . For each trial , we enrolled a convenience sample of 2 internal medicine practice s , and their interested physicians and male patients with no prior history of prostate cancer ( for a total of 4 practice s , 28 physicians , and 128 men across trials ) . Within each practice site , we r and omized men to either 1 ) a video-based decision aid and research er-led coaching session or 2 ) a highway safety video . Physicians at each site received a 1-hour educational session on prostate cancer and SDM . To assess intervention effects , we measured key components of SDM , intent to be screened , and actual screening . After finding that results did not vary by trial , we combined data across sites , adjusting for the r and om effects of both practice and physician . Results Compared to an attention control , our prostate cancer screening intervention increased men ’s perceptions that screening is a decision ( absolute difference + 41 % ; 95 % CI 25 to 57 % ) and men ’s knowledge about prostate cancer screening ( absolute difference + 34 % ; 95 % CI 19 % to 50 % ) , but had no effect on men ’s self-reported participation in shared decisions or their participation at their preferred level . Overall , the intervention decreased screening intent ( absolute difference −34 % ; 95 % CI −50 % to −18 % ) and actual screening rates ( absolute difference −22 % ; 95 % CI −38 to −7 % ) with no difference in effect by frame . Conclusions SDM interventions can increase men ’s knowledge , alter their perceptions of prostate cancer screening , and reduce actual screening . However , they may not guarantee an increase in shared decisions . Trial registration # ABSTRACT Despite increased interest among the public in breast cancer genetic risk and genetic testing , there are limited services to help women make informed decisions about genetic testing . This study , conducted with female callers ( N = 279 ) to the National Cancer Institute 's ( NCI 's ) Atlantic Region Cancer Information Service ( CIS ) , developed and evaluated a theory-based , educational intervention design ed to increase callers ' underst and ing of the following : ( a ) the kinds of information required to determine inherited risk ; ( b ) their own personal family history of cancer ; and ( c ) the benefits and limitations of genetic testing . Callers requesting information about breast/ovarian cancer risk , risk assessment services , and genetic testing were r and omized to either : ( 1 ) st and ard care or ( 2 ) an educational intervention . Results show that the educational intervention reduced intention to obtain genetic testing among women at average risk and increased intention among high-risk women at 6 months . In addition , high monitors , who typically attend to and seek information , demonstrated greater increases in knowledge and perceived risk over the 6-month interval than low monitors , who typically are distracted from information . These findings suggest that theoretically design ed interventions can be effective in helping women underst and their cancer risk and appropriate risk assessment options and can be implemented successfully within a service program like the CIS Purpose . To conduct a pilot test of a decision aid design ed to help patients choose among currently recommended colorectal cancer screening programs . Methods . R and omized controlled trial comparing a patient decision aid based on multi criteria decision-making theory with a simple educational intervention . Patient population . 96 patients at average risk for colorectal cancer seen in an Internal Medicine practice in Rochester , New York . Outcome measures . The two primary outcome measures were patient decision process and the decision outcome . Patient decision process was assessed using the decisional conflict scale . Decision outcome was defined as the proportion of colorectal cancer screening plans carried out . Results . After controlling for the effects of the physicians in a factorial analysis of variance , patients who used the decision aid had lower decisional conflict regarding colorectal cancer screening decisions ( F ratio6.47 , P = 0.01 ) due to increased knowledge , better clarity of values , and higher ratings of the quality of the decisions they made . There was no difference between the groups in decision outcomes : 52 % of patients in the control group and 49 % in the experimental group completed planned screening tests ( P = 1.0 ) . Conclusions . In a pilot study , a multi criteria -based patient decision aid for colorectal cancer screening improved patients ’ decision-making processes but had no effect on the implementation of screening plans There is an ever-growing trend toward more patient involvement in making health care decisions . This trend has been accompanied by the development of “ informed decision-making ” interventions to help patients become more engaged and comfortable with making these decisions . We describe the effects of a prostate cancer screening decision aid on knowledge , beliefs about screening , risk perception , control preferences , decisional conflict , and decisional anxiety . Data were collected from 200 males aged 50–70 years in the general population who r and omly were assigned to exposure to the decision aid or no exposure as a control condition . A Solomon four-group design was used to test for possible pretest sensitization effects and to assess the effects of exposure to the decision aid . No significant pretest sensitization effects were found . Analysis of the exposure effects found that knowledge increased significantly for those exposed to the decision aid compared with those unexposed . Exposure to the decision aid also had some influence on decreasing both decisional conflict and decisional anxiety . Decision aids can play an important role in increasing patients ' knowledge and decreasing anxiety when asked to make health care decisions Background Whether early detection and treatment of prostate cancer ( PCa ) will reduce disease-related mortality remains uncertain . As a result , tools are needed to facilitate informed decision making . While there have been several decision aids ( DAs ) developed and tested , very few have included an exercise to help men clarify their values and preferences about PCa screening . Further , only one DA has utilized an interactive web-based format , which allows for an expansion and customization of the material . We describe the development of two DAs , a booklet and an interactive website , each with a values clarification component and design ed for use in diverse setting s. Methods We conducted two feasibility studies to assess men 's ( 45 - 70 years ) Internet access and their willingness to use a web- vs. a print-based tool . The booklet was adapted from two previous versions evaluated in r and omized controlled trials ( RCTs ) and the website was created to closely match the content of the revised booklet . Usability testing was conducted to obtain feedback regarding draft versions of the material s. The tools were also review ed by a plain language expert and the interdisciplinary research team . Feedback on the content and presentation led to iterative modifications of the tools . Results The feasibility studies confirmed that the Internet was a viable medium , as the majority of men used a computer , had access to the Internet , and Internet use increased over time . Feedback from the usability testing on the length , presentation , and content of the material s was incorporated into the final versions of the booklet and website . Both the feasibility studies and the usability testing highlighted the need to address men 's informed decision making regarding screening . Conclusions Informed decision making for PCa screening is crucial at present and may be important for some time , particularly if a definitive recommendation either for or against screening does not emerge from ongoing prostate cancer screening trials . We have detailed our efforts at developing print- and web-based DAs to assist men in determining how to best meet their PCa screening preferences . Following completion of our ongoing RCT design ed to test these material s , our goal will be to develop a dissemination project for the more effective tool . Trial Registration OBJECTIVE Screening asymptomatic men for prostate cancer is controversial and informed decision making is recommended . Within two prostate cancer screening programs , we evaluated the impact of a print-based decision aid ( DA ) on decision-making outcomes . METHODS Men ( N=543 ) were 54.9 ( SD=8.1 ) years old and 61 % were African-American . The 2(booklet type : DA vs. usual care (UC)) × 2(delivery mode : Home vs. Clinic ) r and omized controlled trial assessed decisional and screening outcomes at baseline , 2-months , and 13-months . RESULTS Intention-to-treat linear regression analyses using generalized estimating equations revealed that DA participants reported improved knowledge relative to UC ( B=.41 , p<.05 ) . For decisional conflict , per- protocol analyses revealed a group by time interaction ( B=-.69 , p<.05 ) , indicating that DA participants were less likely to report decisional conflict at 2-months compared to UC participants ( OR=.49 , 95 % CI : .26-.91 , p<.05 ) . CONCLUSION This is the first r and omized trial to evaluate a DA in the context of free mass screening , a challenging setting in which to make an informed decision . The DA was highly utilized by participants , improved knowledge and reduced decisional conflict . PRACTICE IMPLICATION S These results are valuable in underst and ing ways to improve the decisions of men who seek screening and can be easily implemented within many setting OBJECTIVE Genetic testing is increasingly part of routine clinical care for women with a family history of breast cancer . Given their substantially elevated risk for breast cancer , BRCA1/BRCA2 mutation carriers must make the difficult decision whether or not to opt for risk reducing mastectomy . To help BRCA1/2 carriers make this decision , the authors developed a computer-based interactive decision aid that was tested against usual care in a r and omized controlled trial . DESIGN After the completion of genetic counseling , 214 female ( aged 21 - 75 ) BRCA1/BRCA2 mutation carriers were r and omized to Usual Care ( UC ; N = 114 ) or Usual Care plus Decision Aid ( DA ; N = 100 ) arms . UC participants received no additional intervention . DA participants were sent the CD-ROM DA to view at home . MAIN OUTCOME MEASURES The authors measured final management decision , decisional conflict , decisional satisfaction , and receipt of risk reducing mastectomy at 1- , 6- , and 12-months postr and omization . RESULTS Longitudinal analyses revealed that the DA was effective among carriers who were initially undecided about how to manage their breast cancer risk . Within this group , the DA led to an increased likelihood of reaching a management decision ( OR = 3.09 , 95 % CI = 1.62 , 5.90 ; p < .001 ) , decreased decisional conflict ( B = -.46 , z = -3.1 , p < 002 ) , and increased satisfaction ( B = .27 , z = 3.1 , p = .002 ) compared to UC . Among carriers who had already made a management decision by the time of r and omization , the DA had no benefit relative to UC . CONCLUSION These results demonstrate that BRCA1/BRCA2 mutation carriers who are having difficulty making a breast cancer risk management decision can benefit from adjunct decision support Background Patients are being encouraged to go online to obtain health information and interact with their health care systems . However , a 2014 survey found that less than 60 % of American adults aged 65 and older use the Internet , with much lower usage among black and Latino seniors compared with non-Hispanic white seniors , and among older versus younger seniors . Objective Our aims were to ( 1 ) identify race/ethnic and age cohort disparities among seniors in use of the health plan ’s patient portal , ( 2 ) determine whether race/ethnic and age cohort disparities exist in access to digital devices and preferences for using email- and Web-based modalities to interact with the health care system , ( 3 ) assess whether observed disparities in preferences and patient portal use are due simply to barriers to access and inability to use the Internet , and ( 4 ) learn whether older adults not currently using the health plan ’s patient portal or website have a potential interest in doing so in the future and what kind of support might be best suited to help them . Methods We conducted two studies of seniors aged 65 - 79 years . First , we used administrative data about patient portal account status and utilization in 2013 for a large cohort of English-speaking non-Hispanic white ( n=183,565 ) , black ( n=16,898 ) , Latino ( n=12,409 ) , Filipino ( n=11,896 ) , and Chinese ( n=6314 ) members of the Kaiser Permanente Northern California health plan . Second , we used data from a mailed survey conducted in 2013 - 2014 with a stratified r and om sample of this population ( final sample : 849 non-Hispanic white , 567 black , 653 Latino , 219 Filipino , and 314 Chinese ) . These data were used to examine race/ethnic and age disparities in patient portal use and readiness and preferences for using digital communication for health-related purpose s. Results Adults aged 70 - 74 and 75 - 79 were significantly less likely than 65 - 69 year olds to be registered to use the patient portal , and among those registered , to have used the portal to send messages , view lab test results , or order prescription refills . Across all age groups , non-Hispanic whites and Chinese seniors were significantly more likely than black , Latino , and Filipino seniors to be registered and to have performed these actions . The survey found that black , Latino , and Filipino seniors and those 75 years old and older were significantly less likely to own digital devices ( eg , computers , smartphones ) , use the Internet and email , and be able and willing to use digital technology to perform health care-related tasks , including obtaining health information , than non-Hispanic whites , Chinese , and younger seniors ( aged 65 - 69 ) , respectively . The preference for using non-digital modalities persisted even among Internet users . Conclusions Health plans , government agencies , and other organizations that serve diverse groups of seniors should include social determinants such as race/ethnicity and age when monitoring trends in eHealth to ensure that eHealth disparities do not induce greater health status and health care disparities between more privileged and less privileged groups OBJECTIVE The purpose of this trial was to compare usual patient education plus the Internet-based Personal Patient Profile-Prostate , vs. usual education alone , on conflict associated with decision making , plus explore time-to-treatment , and treatment choice . METHODS A r and omized , multi-center clinical trial was conducted with measures at baseline , 1- , and 6 months . Men with newly diagnosed localized prostate cancer ( CaP ) who sought consultation at urology , radiation oncology , or multi-disciplinary clinics in 4 geographically-distinct American cities were recruited . Intervention group participants used the Personal Patient Profile-Prostate , a decision support system comprised of customized text and video coaching regarding potential outcomes , influential factors , and communication with care providers . The primary outcome , patient-reported decisional conflict , was evaluated over time using generalized estimating equations to fit generalized linear models . Additional outcomes , time-to-treatment , treatment choice , and program acceptability/usefulness , were explored . RESULTS A total of 494 eligible men were r and omized ( 266 intervention ; 228 control ) . The intervention reduced adjusted decisional conflict over time compared with the control group , for the uncertainty score ( estimate -3.61 ; ( confidence interval , -7.01 , 0.22 ) , and values clarity ( estimate -3.57 ; confidence interval ( -5.85,-1.30 ) . Borderline effect was seen for the total decisional conflict score ( estimate -1.75 ; confidence interval ( -3.61,0.11 ) . Time-to-treatment was comparable between groups , while undecided men in the intervention group chose brachytherapy more often than in the control group . Acceptability and usefulness were highly rated . CONCLUSION The Personal Patient Profile-Prostate is the first intervention to significantly reduce decisional conflict in a multi-center trial of American men with newly diagnosed localized CaP. Our findings support efficacy of P3P for addressing decision uncertainty and facilitating patient selection of a CaP treatment that is consistent with the patient values and preferences Background Men diagnosed with localized prostate cancer ( LPC ) can choose from multiple treatment regimens and are faced with a decision in which medical factors and personal preferences are important . The Personal Patient Profile-Prostate ( P3P ) is a computerized decision aid for men with LPC that focuses on personal preferences . We determined whether the P3P intervention improved the concordance of treatment choice with self-reported influential side-effects compared with a control group . Methods English/Spanish-speaking men diagnosed with LPC ( 2007–2009 ) from four US cities were enrolled into a r and omized trial and followed through 6-months via mailed or online question naire . Men were r and omized to receive the P3P intervention or st and ard education plus links to reputable websites . We classified choice as concordant if men were concerned with ( a ) sexual function and chose external beam radiotherapy or brachytherapy , ( b ) bowel function and chose prostatectomy , ( c ) sex , bowel , and /or bladder function and chose active surveillance , or ( d ) not concerned with any side effect and chose any treatment . Using logistic regression , we calculated odds ratios ( OR ) and 95 % confidence intervals ( CI ) for the association between the P3P intervention and concordance . Results Of 448 men , most were < 65 years , non-Hispanic white , had multiple physician consultations prior to enrollment , and chose a treatment discordant with concerns about potential side effects . There was no significant difference in concordance between the intervention ( 45 % ) and control ( 50 % ) group ( OR = 0.82 ; 95%CI = 0.56 , 1.2 ) . Conclusions The P3P intervention did not improve concordance between potential side effects and treatment choice . Information and /or physician consultation immediately after diagnosis was likely to influence decisions despite concerns about side effects . The intervention may be more effective before the first treatment options consultation . Trial registration NCT00692653 http:// clinical Objective : To evaluate a decision aid ( DA ) design ed to promote informed decision making for prostate cancer screening . Methods : Twelve work sites were r and omly assigned to an intervention or nonintervention comparison condition . Intervention sites received access to a computer-tailored DA at the workplace . Male employees age 45 years and above ( n = 625 ) completed surveys at baseline and at 3-month follow-up , documenting aspects of informed decision making . Results : Using an intention-to-treat analysis , men in the intervention group were significantly more likely to have made a screening decision and to have improved knowledge without increased decisional conflict , relative to men in the comparison group . These changes were observed despite the fact that only 30 % of men in intervention sites used the DA . Among DA users , similar improvements were observed , although the magnitudes of changes were substantially greater , and significant improvements in decision self-efficacy were observed . Conclusions : A DA offered in the workplace promoted decision making , improved knowledge , and increased decision self-efficacy among users , without increasing decisional conflict . However , participation was suboptimal , suggesting that better methods for engaging men in workplace interventions are needed . Impact Statement : This trial shows the efficacy of a computer-tailored DA in promoting informed decisions about prostate cancer screening . The DA was delivered through work sites , thereby providing access to re sources required to participate in informed decision making without requiring a medical appointment . However , participation rates were suboptimal , and additional strategies for engaging men are needed . Cancer Epidemiol Biomarkers Prev ; 19(9 ) ; 2172–86 . © 2010 AACR OBJECTIVE To evaluate an entertainment-based patient decision aid for early stage breast cancer surgery in low health literacy patients . METHODS Newly diagnosed female patients with early stage breast cancer from two public hospitals were r and omized to receive an entertainment-based decision aid for breast cancer treatment along with usual care ( intervention arm ) or to receive usual care only ( control arm ) . Pre-decision ( baseline ) , pre-surgery , and 1-year follow-up assessment s were conducted . RESULTS Patients assigned to the intervention arm of the study were more likely than the controls to choose mastectomy rather than breast-conserving surgery ; however , they appeared better informed and clearer about their surgical options than women assigned to the control group . No differences in satisfaction with the surgical decision or the decision-making process were observed between the patients who viewed the intervention and those assigned to the control group . CONCLUSIONS Entertainment education may be a desirable strategy for informing lower health literate women about breast cancer surgery options . PRACTICE IMPLICATION S Incorporating patient decision aids , particularly computer-based decision aids , into st and ard clinical practice remains a challenge ; however , patients may be directed to view programs at home or at public locations ( e.g. , libraries , community centers ) Abstract BACKGROUND : Little is known about the relative advantages of video versus internet-based decision aids to facilitate shared medical decision making . This study compared internet and video patient education modalities for men considering the prostate specific antigen ( PSA ) test . METHODS : Two hundred and twenty-six men , aged 50 years or older , and scheduled to complete a physical examination at an HMO Health Appraisal Clinic were r and omly assigned to access a website ( N=114 ) or view a 23-minute videotape in the clinic ( N=112 ) prior to deciding whether they wanted to be screened for prostate cancer . RESULTS : There were no between-groups differences in participants ’ ratings of convenience , effort , or satisfaction following exposure to the decision aid . Participants assigned to the video group were more likely to review the material s than individuals assigned to the internet group ( 98.2 % vs 53.5 % ) . Participants in the video group showed significantly greater increases in PSA knowledge and were more likely to decline the PSA test than individuals assigned to the internet group . However , participants in the internet group who review ed the entire online presentation showed similar increases in PSA knowledge as video participants . Only 5 % of all participants visited other websites to inform themselves about the PSA test . CONCLUSIONS : Overall , the video was significantly more effective than the Internet in educating participants about benefits and risks of PSA screening OBJECTIVE This r and omized trial was conducted to assess the impact of a mediated decision support intervention on primary care patient prostate cancer screening knowledge , decisional conflict , informed decision making ( IDM ) , and screening . METHODS Before a routine office visit , 313 male patients eligible for prostate cancer screening completed a baseline telephone survey and received a mailed brochure on prostate cancer screening . At the visit , participants were r and omized to either an enhanced intervention ( EI ) or a st and ard intervention ( SI ) group . Before meeting with their physician , EI Group men had a nurse-led " decision counseling " session , while SI Group men completed a practice satisfaction survey . An endpoint survey was administered . Survey data , encounter audio-recordings , and chart audit data were used to assess study outcomes . RESULTS Knowledge increased in the EI Group ( mean difference of + 0.8 on a 10-point scale , p=0.001 ) , but decisional conflict did not change ( mean difference of -0.02 on a 4-point scale , p=0.620 ) . The EI Group had higher IDM ( rate ratio=1.30 , p=0.029 ) and lower screening ( odds ratio=0.67 , p=0.102 ) . CONCLUSION Nurse-mediated decision counseling increased participant prostate cancer screening knowledge , and influenced informed decision making and screening . PRACTICE IMPLICATION S Nurses trained in decision counseling can facilitate shared decision making about screening BACKGROUND Shared decision making ( SDM ) is a widely recommended yet unproven strategy for increasing colorectal cancer ( CRC ) screening uptake . Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results . PURPOSE To assess the impact of decision aid-assisted SDM on CRC screening uptake . DESIGN RCT . SETTING / PARTICIPANTS The study was conducted at an urban , academic safety-net hospital and community health center between 2005 and 2010 . Participants were asymptomatic , average-risk patients aged 50 - 75 years due for CRC screening . INTERVENTION Study participants ( n=825 ) were r and omized to one of two intervention arms ( decision aid plus personalized risk assessment or decision aid alone ) or control arm . The interventions took place just prior to a routine office visit with their primary care providers . MAIN OUTCOME MEASURES The primary outcome was completion of a CRC screening test within 12 months of the study visit . Logistic regression was used to identify predictors of test completion and mediators of the intervention effect . Analysis was completed in 2011 . RESULTS Patients in the decision-aid group were more likely to complete a screening test than control patients ( 43.1 % vs 34.8 % , p=0.046 ) within 12 months of the study visit ; conversely , test uptake for the decision aid and decision aid plus personalized risk assessment arms was similar ( 43.1 % vs 37.1 % , p=0.15 ) . Assignment to the decision-aid arm ( AOR=1.48 , 95 % CI=1.04 , 2.10 ) , black race ( AOR=1.52 , 95 % CI=1.12 , 2.06 ) and a preference for a patient-dominant decision-making approach ( AOR=1.55 , 95 % CI=1.02 , 2.35 ) were independent determinants of test completion . Activation of the screening discussion and enhanced screening intentions mediated the intervention effect . CONCLUSIONS Decision aid-assisted SDM has a modest impact on CRC screening uptake . A decision aid plus personalized risk assessment tool is no more effective than a decision aid alone . TRIAL REGISTRATION This study is registered at www . clinical trials.govNCT00251862 Background . This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aim ed at increasing patient participation in these discussion Abstract OBJECTIVE : To assess the effect of video and pamphlet interventions on patient prostate cancer ( CaP ) screening knowledge , decision-making participation , preferences , and behaviors . DESIGN : R and omized , controlled trial . SETTING : Four midwestern Veterans Affairs medical facilities . PATIENTS / PARTICIPANTS : One thous and , one hundred fifty-two male veterans age 50 and older with primary care appointments at participating facilities were r and omized and 893 completed follow-up . INTERVENTIONS : Patients were r and omized to mailed pamphlet , mailed video , or usual care/control . MEASUREMENTS AND MAIN RESULTS : Outcomes assessed by phone survey 2 weeks postintervention included a 10-item knowledge index ; correct responses to questions on CaP natural history , treatment efficacy , the prostate-specific antigen ( PSA ) ’s predictive value , and expert disagreement about the PSA ; whether screening was discussed with provider ; screening preferences ; and PSA testing rates . Mean knowledge index scores were higher for video ( 7.44 ; P=.001 ) and pamphlet ( 7.26 ; P=.03 ) subjects versus controls ( 6.90 ) . Video and pamphlet subjects reported significantly higher percentages of correct responses relative to controls to questions on CaP natural history ( 63 % , 63 % , and 54 % , respectively ) ; treatment efficacy ( 19 % , 20 % , and 5 % ) , and expert disagreement ( 28 % , 19 % , and 8 % ) , but not PSA accuracy ( 28 % , 22 % , and 22 % ) . Pamphlet subjects were more likely than controls to discuss screening with their provider ( 41 % vs 32 % ; P=.03 ) but video subjects were not ( 35 % ; P=.33 ) . Video and pamphlet subjects were less likely to intend to have a PSA , relative to controls ( 63 % , 65 % , and 74 % , respectively ) . PSA testing rates did not differ significantly across groups . CONCLUSIONS : Mailed interventions enhance patient knowledge and self-reported participation in decision making , and alter screening preferences . The pamphlet and video interventions evaluated are comparable in effectiveness . The lower-cost pamphlet approach is an attractive option for clinics with limited re sources BACKGROUND In response to the isolation of the BRCA1 gene , a breast-ovarian cancer-susceptibility gene , biotechnology companies are already marketing genetic tests to health care providers and to the public . Initial studies indicate interest in BRCA1 testing in the general public and in population s at high risk . However , the optimal strategies for educating and counseling individuals have yet to be determined . PURPOSE Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and /or ovarian cancer . METHODS A r and omized trial design was used to evaluate the effects of education only ( educational approach ) and education plus counseling ( counseling approach ) , as compared with a waiting-list ( control ) condition ( n = 400 for all groups combined ) . The educational approach review ed information about personal risk factors , inheritance of cancer susceptibility , the benefits , limitations , and risks of BRCA1 testing , and cancer screening and prevention options . The counseling approach included this information , as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing . Data on knowledge of inherited cancer and BRCA1 test characteristics , perceived risk , perceived benefits , limitations and risks of BRCA1 testing , and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up . Provision of a blood sample for future testing served as a proxy measure of intention to be tested ( in the education and counseling arms of the study ) . The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling ( for the blood sample outcome ) . All P values are for two-sided tests . RESULTS The educational and counseling approaches both led to significant increases in knowledge , relative to the control condition ( P < .001 for both ) . The counseling approach , but not the educational approach , was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing ( P < .01 ) and decreases in perceived benefits ( P < .05 ) . However , neither approach produced changes in intentions to have BRCA1 testing . Prior to and following both education only and education plus counseling , approximately one half of the participants stated that they intended to be tested ; after the session , 52 % provided a blood sample . CONCLUSIONS St and ard educational approaches may be equally effective as exp and ed counseling approaches in enhancing knowledge . Since knowledge is a key aspect of medical decision-making , st and ard education may be adequate in situations where genetic testing must be streamlined . On the other h and , it has been argued that optimal decision-making requires not only knowledge , but also a reasoned evaluation of the positive and negative consequences of alternate decisions . Although the counseling approach is more likely to achieve this goal , it may not diminish interest in testing , even among women at low to moderate risk . Future research should focus on the merits of these alternate approaches for subgroups of individuals with different background s who are being counseled in the variety of setting s where BRCA1 testing is likely to be offered CONTEXT As the availability of and dem and for genetic testing for hereditary cancers increases in primary care and other clinical setting s , alternative or adjunct educational methods to traditional genetic counseling will be needed . OBJECTIVE To compare the effectiveness of a computer-based decision aid with st and ard genetic counseling for educating women about BRCA1 and BRCA2 genetic testing . DESIGN R and omized controlled trial conducted from May 2000 to September 2002 . SETTING AND PARTICIPANTS Outpatient clinics offering cancer genetic counseling at 6 US medical centers enrolled 211 women with personal or family histories of breast cancer . INTERVENTIONS St and ard one-on-one genetic counseling ( n = 105 ) or education by a computer program followed by genetic counseling ( n = 106 ) . MAIN OUTCOME MEASURES Participants ' knowledge , risk perception , intention to undergo genetic testing , decisional conflict , satisfaction with decision , anxiety , and satisfaction with the intervention . Counselor group measures were administered at baseline and after counseling . Computer group measures were administered at baseline , after computer use , and after counseling . Testing decisions were assessed at 1 and 6 months . Outcomes were analyzed by high vs low risk of carrying a BRCA1 or BRCA2 mutation . RESULTS Both groups had comparable demographics , prior computer experience , medical literacy , and baseline knowledge of breast cancer and genetic testing , and both counseling and computer use were rated highly . Knowledge scores increased in both groups ( P<.001 ) regardless of risk status , and change in knowledge was greater in the computer group compared with the counselor group ( P = .03 ) among women at low risk of carrying a mutation . Perception of absolute risk of breast cancer decreased significantly after either intervention among all participants . Intention to undergo testing decreased significantly after either intervention among low-risk but not high-risk women . The counselor group had lower mean scores on a decisional conflict scale ( P = .04 ) and , in low-risk women , higher mean scores on a satisfaction-with-decision scale ( P = .001 ) . Mean state anxiety scores were reduced by counseling but were within normal ranges for both groups at baseline and after either intervention , regardless of risk status . CONCLUSIONS An interactive computer program was more effective than st and ard genetic counseling for increasing knowledge of breast cancer and genetic testing among women at low risk of carrying a BRCA1 or BRCA2 mutation . However , genetic counseling was more effective than the computer at reducing women 's anxiety and facilitating more accurate risk perceptions . These results suggest that this computer program has the potential to st and alone as an educational intervention for low-risk women but should be used as a supplement to genetic counseling for those at high risk PURPOSE Many clinicians lack re sources to engage patients in shared decision making for prostate cancer screening . We sought to evaluate whether previsit educational decision aids facilitate shared decision making . METHODS This r and omized controlled study compared a Web-based and a paper-based decision aid with no previsit education . Men aged 50 to 70 years undergoing a health maintenance examination at a large family practice were enrolled . The primary outcome was patient-reported level of control over the decision to be screened . Secondary outcomes included frequency of screening , patient knowledge , decisional conflict , and time spent discussing screening . RESULTS A total of 497 men participated ( 75 control , 196 brochure , 226 Web site ) . Patients exposed to either aid were no more likely than control patients to report a collaborative decision : 36 % of patients in each group reported equally sharing decision responsibility . Exposure to either decision aid increased patients ’ involvement in decision making compared with the control condition ( Web site , P = .03 ; brochure , P = .03 ) . Only 46 % of control patients reported an active decision-making role , compared with 56 % of Web site and 54 % of brochure patients . Patients exposed to a decision aid answered a greater percentage of knowledge questions correctly ( 54 % control vs 69 % Web site , P < .001 , and vs 69 % brochure , P < .001 ) and were less likely to be screened ( 94 % control vs 86 % Web site , P = .06 , and vs 85 % brochure , P = .04 ) . CONCLUSIONS Patients in the decision aid groups were more informed and more engaged in the screening decision than their control counterparts . Exposure did not promote shared decision-making control , however . Whether shared decision making is the ideal model and how to measure its occurrence are subjects for further research BACKGROUND This study was a r and omized trial to test the impact of an informed decision-making intervention on prostate cancer screening use . METHODS The study population included 242 African-American men from three primary care practice s who were 40 - 69 years of age and had no history of prostate cancer . Participants completed a baseline survey question naire and were r and omly assigned either to a St and ard Intervention ( SI ) group ( N=121 ) or an Enhanced Intervention ( EI ) group ( N=121 ) . An informational booklet was mailed to both groups . EI group men were also offered a screening decision education session . Two outcomes were considered : ( 1 ) complete screening ( i.e. , having a digital rectal exam ( DRE ) and prostate specific antigen ( PSA ) testing ) , and ( 2 ) complete or partial screening ( i.e. , having a PSA test with or without DRE ) . An endpoint chart audit was performed six months after initial intervention contact . The data were analyzed via exact logistic regression . RESULTS Overall , screening use was low among study participants . EI group men had a screening frequency two times greater than that of SI group men , but the difference was not statistically significant : 8 % vs. 4 % ( OR = 1.94 ) fo rcomplete screening , and 19 % vs. 10 % ( OR = 2.08 ) for complete or partial screening . Multivariable analyses showed that being in the EI group and primary care practice were significant predictors of complete or partial screening ( OR = 3.9 and OR = 5.64 , respectively ) . CONCLUSION Prostate cancer screening use may be influenced by exposure to decision education and the influence of screening-related primary care practice factors Introduction Tamoxifen and raloxifene are chemopreventive drugs that can reduce women 's relative risk of primary breast cancer by 50 % ; however , most women eligible for these drugs have chosen not to take them . The reasons for low uptake may be related to women 's knowledge or attitudes towards the drugs . We aim ed to examine the impact of an online breast cancer chemoprevention decision aid ( DA ) on informed intentions and decisions of women at high risk of breast cancer . Methods We conducted a r and omized clinical trial , assessing the effect of a DA about breast cancer chemoprevention on informed choices about chemoprevention . Women ( n = 585 ) , 46- to 74-years old old , completed online baseline , post-test , and three-month follow-up question naires . Participants were r and omly assigned to either an intervention group , a st and ard control group that answered questions about chemoprevention at baseline , or a three-month control group that did not answer questions about chemoprevention at baseline . The main outcome measures were whether women 's intentions and decisions regarding chemoprevention drugs were informed , and whether women who viewed the DA were more likely to make informed decisions than women who did not view the DA , using a dichotomous composite variable ' informed choice ' ( yes/no ) to classify informed decisions as those reflecting sufficient knowledge and concordance between a woman 's decision and relevant attitudes . Results Analyses showed that more intervention than st and ard control participants ( 52.7 % versus 5.9 % ) made informed decisions at post-test , P < 0.001 . At the three-month follow-up , differences in rates of informed choice between intervention ( 16.9 % ) and both control groups ( 11.8 % and 8.0 % ) were statistically non-significant , P = 0.067 . Conclusions The DA increased informed decision making about breast cancer chemoprevention , although the impact on knowledge diminished over time . This study was not design ed to determine how much knowledge decision makers must retain over time . Examining informed decisions increases underst and ing of the impact of DAs . A st and ard for defining and measuring sufficient knowledge for informed decisions is needed . Trial registration Clinical Trials.gov : As genetic testing for susceptibility to breast cancer becomes more widespread , alternative methods for educating individuals prior to testing will be needed . Our objective was to compare face-to-face education and counseling by a genetic counselor with education by an interactive computer program , assessing the effects of each on knowledge of breast cancer genetics and intent to undergo genetic testing . We used a r and omized , controlled trial . Seventy-two self-referred women with a first-degree relative with breast cancer received outpatient education and counseling at the Clinical Center of the National Institutes of Health ( NIH ) . Twenty-nine received individualized counseling from a genetic counselor ( counseling group ) , 29 received education from an interactive computer program followed by individualized counseling ( computer group ) , and 14 were controls . Both pre- and postintervention assessment of knowledge about breast cancer genetics and intent to undergo genetic testing were measured . The control group participants correctly answered 74 % of the knowledge questions ; the counselor group , 92 % ; and the computer group , 96 % ( P < .0001 ) . Unadjusted mean knowledge scores were significantly higher in the computer group than the counselor group ( P = .048 ) , but they were equivalent when adjusted for demographic differences ( P = 0.34 ) . Intent to undergo genetic testing was influenced by the interventions : preintervention , a majority in all groups ( 69 % ) indicated that they were likely ( definitely and most likely ) to undergo testing ; after either intervention coupled with counseling , only 44 % indicated that they were likely to do so ( P = .0002 ; odds ratio = 2.8 , 95 % CI = 1.7 - 4.9 ) . We concluded that a computer program can successfully educate patients about breast cancer susceptibility , and , along with genetic counseling , can influence patients ' intentions to undergo genetic testing OBJECTIVE Despite the burden of colorectal cancer and improved health care outcomes with early detection and treatment , screening rates among eligible adults are low . We previously developed through a series of studies an interactive electronic tool , Colorectal Web , to promote colorectal cancer screening . METHOD From May 2002 to December 2003 , we conducted a r and omized controlled trial of Colorectal Web compared to a st and ard Web site on colorectal cancer screening in urban , suburban , and rural communities in Michigan with high colorectal cancer burden . Study participants were age 50 years and older , with no previous colorectal cancer screening . Major outcome was screened for colorectal cancer by 24 weeks post-intervention . RESULTS 174 eligible adults were r and omized and participated . Immediately post-intervention , Colorectal Web participants were significantly more likely to have a preferred colorectal cancer screening method , but this difference did not persist at subsequent follow-up . Eighty-nine participants had been screened for colorectal cancer by 24 weeks post-intervention . The probability of being screened for the Colorectal Web intervention study arm compared to the control is OR=3.23 ( 2.73 - 3.50 95 % Confidence Interval ) . CONCLUSION Colorectal Web is more effective than a st and ard colorectal cancer Web site at prompting previously unscreened individuals to choose a preferred colorectal cancer screening test and to be screened for colorectal cancer OBJECTIVE : To assess the impact of informed consent on elderly patients ’ colorectal cancer ( CRC ) screening preferences . DESIGN : R and omized , controlled trial . SETTING : Four general internal medicine practice s. PATIENTS : We studied 399 elderly patients visiting their primary care provider for routine office visits . INTERVENTIONS : Patients were r and omized to receive either a scripted control message briefly describing CRC screening methods or one of two informational interventions simulating an informed consent presentation about CRC screening . One intervention described CRC mortality risk reduction in relative terms ; the other , in absolute terms . MEASUREMENTS AND MAIN RESULTS : The main outcome measure was intent to begin or continue fecal occult blood testing ( FOBT ) , flexible sigmoidoscopy , or both . There was no difference in screening interest between the control group and the two information groups ( p=.8 ) . The majority ( 63 % ) of patients intended to begin or continue CRC screening . Informed patients were able to gauge more accurately the positive predictive value of screening ( p=.0009 ) . Control patients rated the efficacy of screening higher than did patients receiving relative risk reduction information , who rated it higher than did patients receiving absolute risk reduction information ( p=.0002 ) . CONCLUSIONS : Elderly patients appeared to underst and CRC screening information and use it to gauge the efficacy of screening , but provision of information had no impact on their preferences for screening . In view of the large proportion who preferred not to be screened , we conclude that elderly patients should be involved in the screening decision . However , factors other than provision of information must determine their CRC screening preferences Although tamoxifen can prevent primary breast cancer , few women use it as a preventive measure . A second option , raloxifene , has recently been approved . The objective of the study was to determine women ’s interest in tamoxifen and raloxifene after reading a decision aid ( DA ) describing the risks and benefits of each medication . Women with 5-year risk of breast cancer ≥ 1.66 from two large health maintenance organizations were r and omized to receive a DA versus usual care . After reading an on-line DA that discussed the risks and benefits of tamoxifen and raloxifene , women completed measures of risk perception , decisional conflict , behavioral intentions , and actual behavior related to tamoxifen and raloxifene . 3 months following the intervention , 8.1 % of participants had looked for additional information about breast cancer prevention drugs , and 1.8 % had talked to their doctor about tamoxifen and /or raloxifene . The majority , 54.7 % , had decided to not take either drug , 0.5 % had started raloxifene , and none had started tamoxifen . Participants were not particularly worried about taking tamoxifen or raloxifene and did not perceive significant benefits from taking these drugs . Over 50 % did not perceive a change in their risk of getting breast cancer if they took tamoxifen or raloxifene . After reading a DA about tamoxifen and raloxifene , few women were interested in taking either breast cancer prevention drug The recent identification of several BRCA1/BRCA2 founder mutations among Ashkenazi Jewish individuals has led to increased salience of BRCA1/BRCA2 testing for Jewish individuals . Little is known about interest in BRCA1/BRCA2 testing among Ashkenazi Jews from the general population . Furthermore , previous research has not generally evaluated the impact of education on interest in testing among individuals from the general population . The goal of the current study was to examine whether a brief educational booklet regarding BRCA1/BRCA2 testing would influence knowledge , attitudes , and interest in testing among Ashkenazi Jewish women from the general population PURPOSE The efficacy of prostate cancer screening is uncertain , and professional organizations recommend educating patients about potential harms and benefits . We evaluated the effect of a videotape decision aid on promoting informed decision making about prostate cancer screening among primary care patients . METHODS A group of 160 men , 45 to 70 years of age , with no history of prostate cancer , were r and omized to view or not to view a 20-minute educational videotape before a routine office visit at a university-based family medicine clinic . The subjects were contacted again 1 year after their visit to assess their receipt of prostate cancer screening ( digital rectal examination [ DRE ] or prostate-specific antigen [ PSA ] testing ) , their satisfaction with their screening decision , and knowledge retention since the baseline assessment . RESULTS Follow-up assessment s were completed for 87.5 % of the intervention subjects and 83.8 % of the control subjects . The rate of DRE did not differ between the 2 groups . Prostate-specific antigen testing was reported by 24 of 70 ( 34.3 % ) intervention subjects and 37 of 67 ( 55.2 % ) control subjects ( P = .01 ) . African American men were more likely to have had PSA testing ( 9 of 16 , 56.3 % ) than were white men ( 13 of 46 , 28.3 % ) ( P = .044 ) . Satisfaction with the screening decision did not differ between the study groups . Intervention subjects were more knowledgeable of prostate cancer screening than were control subjects , although these differences declined within 1 year ( P < .001 ) . CONCLUSIONS Decision aids for prostate cancer screening can have a long-term effect on screening behavior and appear to promote informed decision making BACKGROUND Colorectal cancer ( CRC ) screening reduces mortality yet remains underutilized . Low health literacy may contribute to this underutilization by interfering with patients ' ability to underst and and receive preventive health services . PURPOSE To determine if a web-based multimedia CRC screening patient decision aid , developed for a mixed-literacy audience , could increase CRC screening . DESIGN RCT . Patients aged 50 - 74 years and overdue for CRC screening were r and omized to the web-based decision aid or a control program seen immediately before a scheduled primary care appointment . SETTING / PARTICIPANTS A large community-based , university-affiliated internal medicine practice serving a socioeconomically disadvantaged population . MAIN OUTCOME MEASURES Patients completed surveys to determine their ability to state a screening test preference and their readiness to receive screening . Charts were abstract ed by masked observers to determine if screening tests were ordered and completed . RESULTS Between November 2007 and September 2008 , a total of 264 patients enrolled in the study . Data collection was completed in 2009 , and data analysis was completed in 2010 . A majority of participants ( mean age=57.8 years ) were female ( 67 % ) , African-American ( 74 % ) , had annual household incomes of < $ 20,000 ( 76 % ) , and had limited health literacy ( 56 % ) . When compared to control participants , more decision-aid participants had a CRC screening preference ( 84 % vs 55 % , p<0.0001 ) and an increase in readiness to receive screening ( 52 % vs 20 % , p=0.0001 ) . More decision-aid participants had CRC screening tests ordered ( 30 % vs 21 % ) and completed ( 19 % vs 14 % ) , but no statistically significant differences were seen ( AOR=1.6 , 95 % CI=0.97 , 2.8 , and AOR=1.7 , 95 % CI=0.88 , 3.2 , respectively ) . Similar results were found across literacy levels . CONCLUSIONS The web-based decision aid increased patients ' ability to form a test preference and their intent to receive screening , regardless of literacy level . Further study should examine ways the decision aid can be combined with additional system changes to increase CRC screening BACKGROUND We conducted a r and omized controlled trial to evaluate the effects of patient decision support Web sites on decision quality for men considering prostate cancer screening . METHODS Men older than 50 years ( N = 611 ) were r and omly assigned to 1 of 4 Internet conditions : traditional didactic decision aid providing information about prostate-specific antigen ( PSA ) screening options and outcomes ; chronic disease trajectory model for prostate cancer followed by a time-trade-off exercise ; both the didactic decision aid and the chronic disease trajectory model ; or links to public prostate cancer-specific Web sites from credible sources ( control condition ) . Participants completed question naires at baseline and after their physical examination . Primary outcome measures were PSA test choice , prostate cancer treatment preferences , knowledge and concern about prostate cancer , and decisional conflict . RESULTS Participants assigned to view public Web sites were less likely to review information ( 116 participants [ 76.8 % ] review ed ) than those assigned to experimental groups ( 399 [ 86.7 % ] review ed ; P = .004 ) . Greater reductions in PSA screening from pretest to posttest were observed among participants assigned to the traditional decision aid ( -9.1 % ) or chronic disease trajectory model ( -8.7 % ) , compared with participants assigned to the combination ( -5.3 % ) or control ( -3.3 % ) groups ( P = .047 ) . Preferences for watchful waiting increased significantly in all 4 groups ( baseline , 219 [ 35.8 % ] ; follow-up , 303 [ 66.2 % ] ; P < .001 ) . Knowledge scores were lowest for those assigned to public Web sites ( mean [ SD ] score , 7.49 [ 0.19 ] of questions correct ) and highest for the traditional decision aid ( 8.65 [ 0.18 ] of questions correct ; P = .005 ) . CONCLUSION Public Web sites about prostate cancer provide less effective decision support than a specially design ed Internet decision aid OBJECTIVE To assess the impact of Guide to Decide ( GtD ) , a web-based , personally-tailored decision aid design ed to inform women 's decisions about prophylactic tamoxifen and raloxifene use . METHODS Postmenopausal women , age 46 - 74 , with BCRAT 5-year risk ≥ 1.66 % and no prior history of breast cancer were r and omized to one of three study arms : intervention ( n=690 ) , Time 1 control ( n=160 ) , or 3-month control ( n=162 ) . Intervention participants viewed GtD prior to completing a post-test and 3 month follow-up assessment . Controls did not . We assessed the impact of GtD on women 's decisional conflict levels and treatment decision behavior at post-test and at 3 months , respectively . RESULTS Intervention participants had significantly lower decisional conflict levels at post-test ( p<0.001 ) and significantly higher odds of making a decision about whether or not to take prophylactic tamoxifen or raloxifene at 3-month follow-up ( p<0.001 ) compared to control participants . CONCLUSION GtD lowered decisional conflict and helped women at high risk of breast cancer decide whether to take prophylactic tamoxifen or raloxifene to reduce their cancer risk . PRACTICE IMPLICATION S Web-based , tailored decision aids should be used more routinely to facilitate informed medical decisions , reduce patients ' decisional conflict , and empower patients to choose the treatment strategy that best reflects their own values Background Given that no other disease with the high incidence of localized prostate cancer ( LPC ) has so many treatments with so few certainties related to outcomes , many men are faced with assuming some responsibility for the treatment decision along with guidance from clinicians . Men strongly consider their own personal characteristics and other personal factors as important and influential to the decision . Clinical research ers have not developed or comprehensively investigated interventions to facilitate the insight and prioritizing of personal factors along with medical factors that are required of a man in preparation for the treatment decision . Objectives The purpose of this pilot study was to develop and evaluate the feasibility and usability of a Web-based decision support technology , the Personal Patient Profile-Prostate ( P3P ) , in men newly diagnosed with LPC . Methods Use cases were developed followed by infrastructure and content application . The program was provided on a personal desktop computer with a touch screen monitor . Participant responses to the query component of P3P determined the content of the multimedia educational and coaching intervention . The intervention was tailored to race , age , and personal factors reported as influencing the decision . Prepilot usability testing was conducted using a “ think aloud ” interview to identify navigation and content challenges . These issues were addressed prior to deployment in the clinic . A clinical pilot was conducted in an academic medical center where men sought consultation and treatment for LPC . Completion time , missing data , and acceptability were measured . Results Prepilot testing included 4 men with a past diagnosis of LPC who had completed therapy . Technical navigation issues were documented along with confusing content language . A total of 30 additional men with a recent diagnosis of LPC completed the P3P program in clinic prior to consulting with a urologist regarding treatment options . In a mean time of 46 minutes ( SD 13 minutes ) , participants completed the P3P query and intervention components . Of a possible 4560 items for 30 participants , 22 ( 0.5 % ) were missing . Acceptability was reported as high overall . The sections of the intervention reported as most useful were the statistics graphs , priority information topics , and annotated external website links . Conclusions The P3P intervention is a feasible and usable program to facilitate treatment decision making by men with newly diagnosed LPC . Testing in a multisite r and omized trial with a diverse sample is warranted PURPOSE To evaluate the impact of a CD-ROM intervention in the education of patients with suspected Lynch syndrome ( LS ) about microsatellite instability ( MSI ) and immunohisochemistry ( IHC ) testing . PATIENTS AND METHODS Two hundred thirteen patients meeting Bethesda criteria were r and omly assigned to receive either a brief educational session with a health educator ( n = 105 ) or a brief educational session plus a CD-ROM ( n = 108 ) . Assessment s were administered at baseline and 2 weeks post-treatment . Primary outcomes included MSI and IHC knowledge and level of satisfaction with and completeness of the preparation to make the decision for MSI testing . Secondary outcomes included decisional conflict , difficulty making the decision , cancer-specific and global anxiety , and level of discussion about MSI testing with family and friends . RESULTS Participants in the education plus CD-ROM condition reported significant increases in knowledge about the MSI and IHC tests , greater satisfaction with the preparation to make a decision for testing , lower decisional conflict , and greater decisional self-efficacy . The effects of the education plus CD-ROM on most outcomes were not moderated by preintervention levels of exposure to MSI testing , family support for MSI testing , or the family history of cancer . CONCLUSION Incorporation of new media education strategies for individuals at risk for LS may be a valuable component of the informed consent process . As clinical criteria for MSI and IHC testing continue to exp and , the need for alternative educational approaches to meet this increased dem and could be met by the self-administered computer-based strategy that we described This study sought to evaluate a shared decision-making aid for breast cancer prevention care design ed to help women make appropriate prevention decisions by presenting information about risk in context . The decision aid was implemented in a high-risk breast cancer prevention program and pilot-tested in a r and omized clinical trial comparing st and ard consultations to use of the decision aid . Physicians completed training with the decision aid prior to enrollment . Thirty participants enrolled ( 15 per group ) and completed measures of clinical feasibility and effectiveness prior to , immediately after , and at 9 months after their consultations . The decision aid was feasible to use during the consultations as measured by consultation duration , user satisfaction , patient knowledge , and decisional conflict . The mean consultation duration was not significantly different between groups ( 24 minutes for intervention group versus 21 minutes for control group , p = 0.42 ) . The majority found the decision aid acceptable and useful and would recommend it to others . Both groups showed an improvement in breast cancer prevention knowledge postvisit , which was significant in the intervention group ( p = 0.01 ) but not the control group ( p = 0.13 ) . However , the knowledge scores returned to baseline at follow-up in both groups . Decision preference for patients who chose chemoprevention post consultations remained constant at follow-up for the intervention group , but not for the control group . The decision framework provides access to key information during consultations and facilitates the integration of emerging biomarkers in this setting . Initial results suggest that the decision aid is feasible for use in the consultation room . The tendency for the decision choices and knowledge scores to return to baseline at follow-up suggests the need for initial and ongoing prevention decision support OBJECTIVE We assessed the short-term effects of a community-based intervention for Hispanic men to encourage informed decision making ( IDM ) about prostate cancer screening with prostate specific antigen ( PSA ) . METHODS All senior social and housing centers in El Paso , TX were r and omized to intervention , a group-based Spanish language educational program facilitated by promotores ( 12 centers ; 161 men ) [ I 's ] , or to control , promotores-facilitated diabetes video and discussion ( 13 centers ; 160 men ) [ C 's ] . RESULTS Participants had low levels of schooling and baseline knowledge ; 44 % reported previous PSA testing . At post-test , the I 's made large knowledge gains , increased their underst and ing that experts disagree about testing , shifted toward more active decision making roles , were more likely to believe that it is important to weigh the advantages and disadvantages of screening and to anticipate potential screening outcomes in making a decision , and were less likely to consider the screening decision easy . The I 's did not change in their screening intention or the belief that choosing not to be screened could be a responsible choice . CONCLUSIONS A community-based intervention to support IDM for prostate cancer screening can increase knowledge and may promote more active involvement in decision making about prostate cancer screening . Such an approach can increase knowledge and may promote more active involvement in decision making about prostate cancer screening . PRACTICE IMPLICATION S It is feasible to develop and implement a community-based intervention program to promote IDM for prostate cancer screening Background . Eliciting patients ’ preferences within a framework of shared decision making ( SDM ) has been advocated as a strategy for increasing colorectal cancer ( CRC ) screening adherence . Our objective was to assess the effectiveness of a novel decision aid on SDM in the primary care setting . Methods . An interactive , computer-based decision aid for CRC screening was developed and evaluated within the context of a r and omized controlled trial . A total of 665 average-risk patients ( mean age , 57 years ; 60 % female ; 63 % black , 6 % Hispanic ) were allocated to 1 of 2 intervention arms ( decision aid alone , decision aid plus personalized risk assessment ) or a control arm . The interventions were delivered just prior to a scheduled primary care visit . Outcome measures ( patient preferences , knowledge , satisfaction with the decision-making process [ SDMP ] , concordance between patient preference and test ordered , and intentions ) were evaluated using pre study /post study visit question naires and electronic scheduling . Results . Overall , 95 % of patients in the intervention arms identified a preferred screening option based on values placed on individual test features . Mean cumulative knowledge , SDMP , and intention scores were significantly higher for both intervention groups compared with the control group . Concordance between patient preference and test ordered was 59 % . Patients who preferred colonoscopy were more likely to have a test ordered than those who preferred an alternative option ( 83 % v. 70 % ; P < 0.01 ) . Intention scores were significantly higher when the test ordered reflected patient preferences . Conclusions . Our interactive computer-based decision aid facilitates SDM , but overall effectiveness is determined by the extent to which providers comply with patient preferences Background . Increasingly , women with a strong family history of breast cancer are seeking genetic testing as a starting point to making significant decisions regarding management of their cancer risks . Individuals who are found to be carriers of a BRCA1 or BRCA2 mutation have a substantially elevated risk for breast cancer and are frequently faced with the decision of whether to undergo risk-reducing mastectomy . Objective . In order to provide BRCA1/2 carriers with ongoing decision support for breast cancer risk management , a computer-based interactive decision aid was developed and tested against usual care in a r and omized controlled trial . Design . Following genetic counseling , 214 female ( aged 21–75 years ) BRCA1/2 mutation carriers were r and omized to usual care ( UC ; n = 114 ) or usual care plus decision aid ( DA ; n = 100 ) arms . UC participants received no further intervention ; DA participants were sent the CD-ROM – based decision aid to view at home . Main Outcome Measures . The authors measured general distress , cancer-specific distress , and genetic testing – specific distress at 1- , 6- , and 12-month follow-up time points postr and omization . Results . Longitudinal analyses revealed a significant longitudinal impact of the DA on cancer-specific distress ( B = 5.67 , z = 2.81 , P = 0.005 ) , which varied over time ( DA group by time ; B = −2.19 , z = −2.47 , P = 0.01 ) , and on genetic testing – specific distress ( B = 5.55 , z = 2.46 , P = 0.01 ) , which also varied over time ( DA group by time ; B = −2.46 , z = −2.51 , P = 0.01 ) . Individuals r and omized to UC reported significantly decreased distress in the month following r and omization , whereas individuals r and omized to the DA maintained their postdisclosure distress over the short term . By 12 months , the overall decrease in distress between the 2 groups was similar . Conclusion . This report provides new insight into the long-term longitudinal effects of DAs OBJECTIVE To evaluate an entertainment-based patient decision aid for prostate cancer screening among patients with low or high health literacy . METHODS Male primary care patients from two clinical sites , one characterized as serving patients with low health literacy ( n=149 ) and the second as serving patients with high health literacy ( n=301 ) , were r and omized to receive an entertainment-based decision aid for prostate cancer screening or an audiobooklet-control aid with the same learner content but without the entertainment features . Postintervention and 2-week follow-up assessment s were conducted . RESULTS Patients at the low-literacy site were more engaged with the entertainment-based aid than patients at the high-literacy site . Overall , knowledge improved for all patients . Among patients at the low-literacy site , the entertainment-based aid was associated with lower decisional conflict and greater self-advocacy ( i.e. , mastering and obtaining information about screening ) when compared to patients given the audiobooklet . No differences between the aids were observed for patients at the high-literacy site . CONCLUSION Entertainment education may be an effective strategy for promoting informed decision making about prostate cancer screening among patients with lower health literacy . PRACTICE IMPLICATION S As barriers to implementing computer-based patient decision support programs decrease , alternative models for delivering these programs should be explored BACKGROUND Prostate cancer screening with serum prostate-specific antigen ( PSA ) and digital rectal examination ( DRE ) continues to increase . Our goal was to test the effect of a prostate cancer screening decision-aid on patients ' knowledge , beliefs , and use of prostate cancer screening tests . METHODS Our study was a r and omized controlled trial of a prostate cancer screening decision-aid consisting of an illustrated pamphlet as opposed to a comparison intervention . We included 257 men aged 50 to 80 years who were receiving primary care at a Department of Veterans Affairs Hospital in Milwaukee , Wisconsin . The decision-aid provided quantitative outcomes of prostate cancer screening with DRE and PSA . We subsequently evaluated prostate cancer screening knowledge , beliefs , and test use . RESULTS The illustrated pamphlet decision-aid was effective in improving knowledge of prostate cancer screening tests : 95 % of the experimental group were aware of the possibility of false-negative test results compared with 85 % of the comparison group ( P < .01 ) . Ninety-one percent of the experimental group were aware of the possibility of a false-positive screening test result compared with 65 % of the comparison group ( P < .01 ) . However , there was no difference in the use of prostate cancer screening between the experimental ( 82 % ) and comparison ( 84 % ) groups , ( P > .05 ) . CONCLUSIONS When used in a primary care setting , an illustrated pamphlet decision-aid was effective in increasing knowledge of prostate cancer screening tests but did not change the use of these tests OBJECTIVE To describe relationships between use of the Personal Patient Profile-Prostate ( P3P ) decision support system and patient characteristics , and perceived preparation for decision making ( PrepDM ) , satisfaction and decisional regret in the context of prostate cancer treatment choice . METHODS 494 men with localized prostate cancer ( LPC ) were r and omized to receive the P3P intervention or usual care and completed pre-treatment , 1-month and 6-month outcome measures . Multivariable linear regression models were fit for each outcome . RESULTS Physician consult visits prior to enrollment , race/ethnicity , and use of clinic-provided books were significant predictors of perceived PrepDM at 1 month . Prior Internet use and PrepDM significantly predicted 6-month decision satisfaction . Decisional regret was significantly predicted by demographics , anxiety , PrepDM score , and EPIC bowel domain score at 6 months . Use of P3P did not predict any outcome . CONCLUSION While the P3P intervention did not significantly affect the outcomes , pre-enrollment information and preparation were strong predictors of the 1- and 6-month outcomes . Decision regret was significantly influenced by personal characteristics and post-treatment symptoms/side effects . PRACTICE IMPLICATION S Information received and used between biopsy and the treatment options consult visit is likely to make a difference in decision satisfaction IMPORTANCE The conflicting recommendations for prostate cancer ( PCa ) screening and the mixed messages communicated to the public about screening effectiveness make it critical to assist men in making informed decisions . OBJECTIVE To assess the effectiveness of 2 decision aids in helping men make informed PCa screening decisions . DESIGN , SETTING , AND PARTICIPANTS A racially diverse group of male out patients aged 45 to 70 years from 3 sites were interviewed by telephone at baseline , 1 month , and 13 months , from 2007 through 2011 . We conducted intention-to-treat univariate analyses and multivariable linear and logistic regression analyses , adjusting for baseline outcome measures . INTERVENTION R and om assignment to print-based decision aid ( n = 628 ) , web-based interactive decision aid ( n = 625 ) , or usual care ( UC ) ( n = 626 ) . MAIN OUTCOMES AND MEASURES Prostate cancer knowledge , decisional conflict , decisional satisfaction , and whether participants underwent PCa screening . RESULTS Of 4794 eligible men approached , 1893 were r and omized . At each follow-up assessment , univariate and multivariable analyses indicated that both decision aids result ed in significantly improved PCa knowledge and reduced decisional conflict compared with UC ( all P < .001 ) . At 1 month , the st and ardized mean difference ( Cohen ’s d ) in knowledge for the web group vs UC was 0.74 , and in the print group vs UC , 0.73 . Decisional conflict was significantly lower for web vs UC ( d = 0.33 ) and print vs UC ( d = 0.36 ) . At 13 months , these differences were smaller but remained significant . At 1 month , high satisfaction was reported by significantly more print ( 60.4 % ) than web participants ( 52.2 % ; P = .009 ) and significantly more web ( P = .001 ) and print ( P = .03 ) than UC participants ( 45.5 % ) . At 13 months , differences in the proportion reporting high satisfaction among print ( 55.7 % ) compared with UC ( 49.8 % ; P = .06 ) and web participants ( 50.4 % ; P = .10 ) were not significant . Screening rates at 13 months did not differ significantly among groups . CONCLUSIONS AND RELEVANCE Both decision aids improved participants ’ informed decision making about PCa screening up to 13 months later but did not affect actual screening rates . Dissemination of these decision aids may be a valuable public health tool . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00196807 OBJECTIVE To evaluate a patient-educational approach to shared decision making for prostate cancer screening . DESIGN R and omized controlled trial with preoffice visit assessment and 2-week follow-up . SETTING University-based family practice center . PATIENTS Men aged 45 through 70 years with no history of prostate cancer or treatment for prostate disease ( N = 160 ) . Two patients were unavailable for follow-up . INTERVENTION Twenty-minute educational videotape on advantages and disadvantages of prostate-specific antigen ( PSA ) screening for prostate cancer . MAIN OUTCOME MEASURES A measure of patients ' core knowledge of prostate cancer developed for this study , reported preferences for PSA testing , and ratings of the videotape . RESULTS Patients ' core knowledge at baseline was poor . At 2-week follow-up , subjects undergoing videotape intervention showed a 78 % improvement in the number of knowledge questions answered correctly ( P = .001 ) , and knowledge increased about mortality due to early-stage prostate cancer , PSA screening performance , treatment-related complications , and disadvantages of screening . No overall change was observed for control subjects . At follow-up , 48 ( 62 % ) of 78 intervention patients planned to have the PSA test compared with 64 ( 80 % ) of 80 control patients ( 18.5 % absolute reduction ; 95 % confidence interval , 4.6%-32.4 % ; P = .009 ) . Intervention subjects rated favorably the amount of information provided and the clarity , balance , and length of the videotape and would recommend the videotape to others . CONCLUSIONS Patient education regarding the potential benefits and harms of early detection of prostate cancer can lead to more informed decision making . Incorporating the PSA videotape into the periodic health examination for asymptomatic men aged 50 years and older is recommended BACKGROUND Because of the many uncertainties surrounding screening for prostate cancer , authorities recommend that patients be involved in the screening decision . OBJECTIVE To determine the impact of informed consent on patient interest in undergoing prostate-specific antigen ( PSA ) screening . METHODS Men 50 years or older with no prior PSA testing and no history of prostate cancer presenting to 1 of 4 university-affiliated primary care practice s were eligible for enrollment . Patients were r and omized to receive either a scripted informational intervention simulating an informed consent presentation ( intervention group , n = 103 ) or a single sentence about the PSA ( control group , n = 102 ) . The main outcome measure was patient interest in undergoing PSA screening measured on a 5-point Likert scale . RESULTS Patients who received the informational intervention were significantly less interested in undergoing PSA screening than controls ( mean difference in interest , 0.8 on 5-point scale , P < .001 ) . Informed patients were much less likely to indicate high interest in screening ( odds ratio , 0.34 ; 95 % confidence interval , 0.19 - 0.60 ; P < .001 ) . In a multivariate model , family history of prostate cancer was associated with increased interest and advancing age with decreased interest in PSA screening , but the informational intervention remained the strongest predictor of interest . CONCLUSIONS Among primary care patients of predominantly lower socioeconomic status , those who received informed consent were significantly less interested in PSA screening than those who did not . For physicians who offer the PSA as a screening test , this finding highlights the importance of apprising patients of the associated benefits , burdens , and uncertainties and allowing them to participate in the screening decision The authors describe 3 large r and omized trials from the Cancer Information Service Research Consortium . Three web-based multimedia programs are being tested to help newly diagnosed prostate ( Project 1 ) and breast cancer patients ( Project 2 ) make informed treatment decisions and breast cancer patients prepare for life after treatment ( Project 3 ) . Project 3 also tests a telephone callback intervention delivered by a cancer information specialist . All participants receive st and ard print material specific to each project . Preliminary results from the 2-month follow-up interviews are reported for the initial wave of enrolled participants , most of whom were recruited from the Cancer Information Service ( 1 - 800 - 4-CANCER ) telephone information program ( Project 1 : n = 208 ; Project 2 : n = 340 ; Project 3 : n = 792 ) . Self-reported use of the multimedia program was 51 % , 52 % , and 67 % for Projects 1 , 2 , and 3 , respectively . Self-reported use of the print material s ( read all , most , or some ) was 90 % , 85 % , and 83 % for Projects 1 , 2 , and 3 , respectively . The callback intervention was completed by 92 % of Project 3 participants . Among those using the Cancer Information Service Research Consortium interventions , perceived usefulness and benefit was high , and more than 90 % reported that they would recommend them to other cancer patients . The authors present 5 initial lessons learned that may help inform future cancer communications research Background : An interactive digital education aid for breast reconstruction patients was developed because of a perceived need to provide patients with more education regarding the treatment so that they can make better informed treatment decisions . A prospect i ve r and omized study was conducted to assess its effectiveness . Methods : Breast cancer patients who were c and i date s for breast reconstruction were recruited and r and omized into a control group and a study group . Both groups received routine assessment and education in the plastic surgery clinic , but the study group also watched the interactive digital education aid . Question naires assessing knowledge , anxiety , and satisfaction were administered ( 1 ) before the initial plastic surgery consultation , ( 2 ) immediately before surgery , and ( 3 ) 1 month after surgery . Results : A total of 133 women participated , 66 in the control group and 67 in the study group . Women in both groups showed decreased anxiety , increased knowledge , and enhanced satisfaction with their decision-making ability associated with preoperative instructions about reconstructive surgery . However , the study group was significantly more satisfied than the control group with the method of receiving information and showed a less steep learning curve regarding the different techniques of breast reconstruction . They also tended to have a reduced mean level of anxiety and increased satisfaction with the treatment choice compared with the control group . Conclusions : An interactive digital education aid is a beneficial educational adjunct for patients contemplating breast reconstruction . Patients who use an interactive digital education aid demonstrate greater factual knowledge , reduced anxiety , and increased postoperative satisfaction compared with patients given preoperative instructions using st and ard methods alone . The benefit of an interactive digital education aid is expected to be higher in a broad-based practice setting outside of a comprehensive cancer center Background Decision support interventions have been developed to help men clarify their values and make informed decisions about prostate cancer testing , but they seldom target high-risk black and immigrant men . Purpose This study evaluated the efficacy of a decision support intervention focused on prostate cancer testing in a sample of predominantly immigrant black men . Methods Black men ( N = 490 ) were r and omized to tailored telephone education about prostate cancer testing or a control condition . Results Post-intervention , the intervention group had significantly greater knowledge , lower decision conflict , and greater likelihood of talking with their physician about prostate cancer testing than the control group . There were no significant intervention effects on prostate specific antigen testing , congruence between testing intention and behavior , or anxiety . Conclusions A tailored telephone decision support intervention can promote informed decision making about prostate cancer testing in black and predominantly immigrant men without increasing testing or anxiety The U.S. Preventive Services Task Force ( USPSTF ) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms . It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance . The USPSTF does not consider the costs of providing a service in this assessment . The USPSTF recognizes that clinical decisions involve more considerations than evidence alone . Clinicians should underst and the evidence but individualize decision making to the specific patient or situation . Similarly , the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms . Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography ( LDCT ) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years . Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery . ( B recommendation ) See the Clinical Considerations section for suggestions for implementation in practice . See the Figure for a summary of the recommendation and suggestions for clinical practice . Figure . Screening for lung cancer : clinical summary of U.S. Preventive Services Task Force recommendation . Appendix Table 1 describes the USPSTF grade s , and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit . Appendix Table 1 . What the USPSTF Grade s Mean and Suggestions for Practice Appendix Table 2 . USPSTF Levels of Certainty Regarding Net Benefit Supplement . Consumer Fact Sheet . Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States ( 1 ) . The most important risk factor for lung cancer is smoking , which results in approximately 85 % of all U.S. lung cancer cases ( 2 ) . Although the prevalence of smoking has decreased , approximately 37 % of U.S. adults are current or former smokers ( 2 ) . The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older . Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer . Lung cancer has a poor prognosis , and nearly 90 % of persons with lung cancer die of the disease . However , early-stage nonsmall cell lung cancer ( NSCLC ) has a better prognosis and can be treated with surgical resection . Detection Most lung cancer cases are NSCLC , and most screening programs focus on the detection and treatment of early-stage NSCLC . Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer , LDCT has greater sensitivity for detecting early-stage cancer ( 3 ) . Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation , the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths . Direct evidence from a large , well-conducted , r and omized , controlled trial ( RCT ) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population ( 4 ) . The magnitude of benefit to the person depends on that person 's risk for lung cancer because those who are at highest risk are most likely to benefit . Screening can not prevent most lung cancerrelated deaths , and smoking cessation remains essential . Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results , incidental findings , overdiagnosis , and radiation exposure . False-positive LDCT results occur in a substantial proportion of screened persons ; 95 % of all positive results do not lead to a diagnosis of cancer . In a high- quality screening program , further imaging can resolve most false-positive results ; however , some patients may require invasive procedures . The USPSTF found insufficient evidence on the harms associated with incidental findings . Overdiagnosis of lung cancer occurs , but its precise magnitude is uncertain . A modeling study performed for the USPSTF estimated that 10 % to 12 % of screen-detected cancer cases are overdiagnosedthat is , they would not have been detected in the patient 's lifetime without screening . Radiation harms , including cancer result ing from cumulative exposure to radiation , vary depending on the age at the start of screening ; the number of scans received ; and the person 's exposure to other sources of radiation , particularly other medical imaging . USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age , total cumulative exposure to tobacco smoke , and years since quitting smoking . The moderate net benefit of screening depends on limiting screening to persons who are at high risk , the accuracy of image interpretation being similar to that found in the NLST ( National Lung Screening Trial ) , and the resolution of most false-positive results without invasive procedures ( 4 ) . Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking . The best evidence for the benefit of screening comes from the NLST , which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years . As with all screening trials , the NLST tested a specific intervention over a finite period . Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans , the oldest participants in the trial were aged 77 years . The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals , age ranges , smoking histories , and times since quitting . A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms . The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening . This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years . Screening may not be appropriate for patients with substantial comorbid conditions , particularly those at the upper end of the screening age range . The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial . The baseline characteristics of the NLST showed a relatively healthy sample , and fewer than 10 % of enrolled participants were older than 70 years ( 5 ) . Persons with serious comorbid conditions may experience net harm , no net benefit , or at least substantially less net benefit . Similarly , persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program . Assessment of Risk Age , total exposure to tobacco smoke , and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST . Other risk factors include specific occupational exposures , radon exposure , family history , and history of pulmonary fibrosis or chronic obstructive lung disease . The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age , especially after age 60 years . In current and former smokers , age-specific incidence rates increase with age and cumulative exposure to tobacco smoke . Smoking cessation substantially reduces a person 's risk for developing and dying of lung cancer . Among persons enrolled in the NLST , those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit ( 6 ) . A vali date d multivariate model showed that persons in the highest 60 % of risk accounted for 88 % of all deaths preventable by screening . Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons . Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests . Therefore , LDCT is currently the only recommended screening test for lung cancer . Treatment Surgical resection is the current st and ard of care for localized NSCLC . This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy . Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be c and i date s for surgery . Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC . Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer . Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments . Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions . Useful Re sources Clinicians have many re sources to help patients stop smoking . The Centers for Disease Control and Prevention has developed a Web site with many such re sources , including information on tobacco quit lines , available in several language s ( www.cdc.gov/tobacco/campaign/tips ) . Quit |
2,175 | 30,355,391 | In summary , there is limited evidence from intervention studies of effects of dietary factors , other than folic acid , on DNA methylation patterns in humans . | DNA methylation is a key component of the epigenetic machinery that is responsible for regulating gene expression and , therefore , cell function .
Patterns of DNA methylation change during development and ageing , differ between cell types , are altered in multiple diseases and can be modulated by dietary factors .
However , evidence about the effects of dietary factors on DNA methylation patterns in humans is fragmentary .
This study was initiated to collate evidence for causal links between dietary factors and changes in DNA methylation patterns . | BACKGROUND Diet is an important factor in colorectal carcinogenesis ; thus , dietary supplements may have a role in colorectal cancer prevention . OBJECTIVE The objective was to establish the relative luminal , epithelial , and epigenetic consequences of prebiotic , probiotic , and synbiotic dietary supplementation in humans . DESIGN This was a r and omized , double-blind , placebo-controlled , 4-wk crossover trial of resistant starch and Bifidobacterium lactis , either alone or as a combined synbiotic preparation , in 20 human volunteers . Rectal biopsy , feces , and serum sample s were collected . The rectal mucosal endpoints were DNA methylation at 16 CpG isl and loci and LINE-1 , epithelial proliferation ( Ki67 immunohistochemistry ) , and crypt cellularity . The fecal endpoints were short-chain fatty acid concentrations , pH , ammonia , and microbiological profiles ( by denaturing gradient gel electrophoresis and sequencing ) . Serum endpoints were a panel of cytokines and high-sensitivity C-reactive protein . RESULTS Seventeen subjects completed the entire study . The synbiotic intervention fostered a significantly different fecal stream bacterial community than did either the prebiotic ( P = 0.032 ) or the probiotic ( P = 0.001 ) intervention alone , in part because of a greater proportion of patients harboring fecal Lachnospiraceae spp . These changes developed in the absence of any significant differences in fecal chemistry . There were no differences in epithelial kinetics . CONCLUSIONS This synbiotic supplementation with B. lactis and resistant starch , in the doses used , induced unique changes in fecal microflora but did not significantly alter any other fecal , serum , or epithelial variables . This trial was registered in the Australian New Zeal and Clinical Trials Registry at www.anzctr.org.au as ACTRN012606000115538 Background : Hyperactive Wnt signaling is frequently observed in colorectal cancer . Higher intakes of dietary fiber [ nondigestible carbohydrates ( NDCs ) ] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway . Objectives : We investigated the effects of supplementing healthy individuals with 2 NDCs [ resistant starch ( RS ) and polydextrose ] on fecal calprotectin concentrations and Wnt pathway – related gene expression . In addition , we determined whether effects on secreted frizzled-related protein 1 ( SFRP1 ) expression are mediated via the epigenetic mechanisms DNA methylation and microRNA expression . Design : In a r and omized , double-blind , placebo-controlled trial ( the Dietary Intervention , Stem cells and Colorectal Cancer ( DISC ) Study ) , 75 healthy participants were supplemented with RS and /or polydextrose or placebo for 50 d in a 2 × 2 factorial design . Pre- and postintervention stool sample s and rectal mucosal biopsies were collected and used to quantify calprotectin and expression of 12 Wnt-related genes , respectively . The expression of 10 microRNAs predicted to target SFRP1 was also quantified by quantitative reverse transcriptase-polymerase chain reaction , and DNA methylation was quantified at 7 CpG sites within the SFRP1 promoter region by pyrosequencing . Results : NDC supplementation did not affect fecal calprotectin concentration . SFRP1 mRNA expression was reduced by both RS ( P = 0.005 ) and polydextrose ( P = 0.053 ) . RS and polydextrose did not affect SFRP1 methylation or alter the expression of 10 microRNAs predicted to target SFRP1 . There were no significant interactions between RS and polydextrose . Conclusions : RS and polydextrose supplementation did not affect fecal calprotectin concentrations . Downregulation of SFRP1 with RS and polydextrose could result in increased Wnt pathway activity . However , effects on Wnt pathway activity and downstream functional effects in the healthy large-bowel mucosa remain to be investigated . The DISC Study was registered at clinical trials.gov as NCT01214681 A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases . There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate . We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine . We also investigated if these effects were modified by MTHFR C677 T genotype . Two hundred sixteen participants out of 818 subjects who had participated in a r and omized double-blind placebo-controlled trial were selected , pre-stratified on MTHFR C677 T genotype and matched on age and smoking status . They were allocated to receive either folic acid ( 0.8 mg/d ; n = 105 ) or placebo treatment ( n = 111 ) for three years . Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed . Global DNA methylation was measured using liquid chromatography-t and em mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine . There was no difference in global DNA methylation between those r and omized to folic acid and those in the placebo group ( difference = 0.008 , 95%CI = −0.05,0.07 , P = 0.79 ) . There was also no difference between treatment groups when we stratified for MTHFR C677 T genotype ( CC , n = 76 ; CT , n = 70 ; TT , n = 70 ) , baseline erythrocyte folate status or baseline DNA methylation levels . In moderately hyperhomocysteinemic men and women , long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes . Clinical Trials.gov Background and aims : A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia . The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a r and omised , double blind , placebo controlled , parallel design . Methods : Subjects were r and omised to receive either 400 μg/day folic acid supplement ( n = 15 ) or placebo ( n = 16 ) for 10 weeks . Genomic DNA methylation , serum and erythrocyte folate , and plasma homocysteine concentrations were measured at baseline and post intervention . Results : Folic acid supplementation increased serum and erythrocyte folate concentrations by 81 % ( 95 % confidence interval ( CI ) 57–104 % ; p<0.001 v placebo ) and 57 % ( 95 % CI 40–74 % ; p<0.001 v placebo ) , respectively , and decreased plasma homocysteine concentration by 12 % ( 95 % CI 4–20 % ; p = 0.01 v placebo ) . Folic acid supplementation result ed in increases in DNA methylation of 31 % ( 95 % CI 16–47 % ; p = 0.05 v placebo ) in leucocytes and 25 % ( 95 % CI 11–39 % ; p = 0.09 v placebo ) in colonic mucosa . Conclusions : These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid Purpose : This study evaluated the effects of black raspberries ( BRBs ) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes , cell proliferation , apoptosis , angiogenesis , and expression of Wnt pathway genes . Experimental Design : Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder ( 60 g/d ) for 1–9 weeks . Methylation status of promoter regions of five tumor suppressor genes was quantified . Protein expression of DNA methyltransferase 1 ( DNMT1 ) and genes associated with cell proliferation , apoptosis , angiogenesis , and Wnt signaling were measured . Results : The methylation of three Wnt inhibitors , SFRP2 , SFRP5 , and WIF1 , upstream genes in Wnt pathway , and PAX6a , a developmental regulator , was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks , but not in all 20 patients with 1–9 weeks of BRB treatment . This was associated with decreased expression of DNMT1 . BRBs modulated expression of genes associated with Wnt pathway , proliferation , apoptosis , and angiogenesis in a protective direction . Conclusions : These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum . While demethylation of genes did not occur in colorectal tissues from all treated patients , the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted . Clin Cancer Res ; 17(3 ) ; 598–610 . © 2010 AACR Background / Aims : Low folate intake may increase risk of colorectal cancer by altering gene-specific methylation in the colon . We determined whether supplementation with physiological doses of folate could alter methylation in the oestrogen receptor 1 ( ESR1 ) and mutL homolog 1 ( MLH1 ) genes in colonic mucosa of subjects with colorectal adenoma . Methods : This was a r and omised , double-blind , placebo-controlled trial . Subjects received either 400 µg/day folic acid ( n = 15 ) or placebo ( n = 14 ) for 10 weeks . Blood and colonic tissue sample s were collected at baseline and after intervention to determine biomarkers of folate and vitamin B12 status , MTHFR C677 T and MS A2756 G genotypes , and ESR1 and MLH1 methylation . Results : Although serum and red cell folate increased ( p < 0.001 vs. placebo ) and plasma homocysteine decreased ( p = 0018 vs. placebo ) in the folic acid group , there were no significant changes in ESR1 ( p = 0.649 vs. placebo ) or MLH1 ( p = 0.211 vs. placebo ) methylation . There was a significant effect of gender on ESR1 methylation ( p = 0.004 ) and significant gender and genotype ( MTHFR C677 T and MS A2756 G ) interactions ( p = 0.04 and p = 0.014 , respectively ) that were independent of treatment group allocation . Conclusions : Short-term folate supplementation in physiological doses decreases plasma homocysteine but has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma . Further studies to investigate the interactions between gender , genotype and DNA methylation suggested in this study are warranted BACKGROUND Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes . Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis . To date , no studies assessing the effect of inadequate folate status on DNA methylation in older women ( aged > 63 y ) have been reported . OBJECTIVE The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women ( aged 60 - 85 y ) to evaluate whether DNA methylation could be used as a functional indicator of folate status . DESIGN Healthy , postmenopausal women ( n = 33 ) consumed a moderately folate-depleted diet ( 118 microg folate/d ) for 7 wk , followed by 7 wk of folate repletion with 200 or 415 microg/d , each provided as 2 different dietary treatments for a total of 4 treatment groups ( n = 30 ) . Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay . RESULTS Incorporation of [(3)H]methyl groups increased significantly ( P : = 0.0025 ) in response to folate depletion , suggesting undermethylation of DNA . No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values . CONCLUSIONS DNA methylation status may be used as a functional indicator of moderately depleted folate status . The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase ( MTHFR ) C677 T genotype . This study investigated the effect of MTHFR C677 T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-12 on uracil misincorporation into DNA and promoter methylation . Subjects ( n = 86 ) with a history of colorectal adenoma and MTHFR CC or TT genotype were r and omly assigned to receive folic acid plus vitamin B-12 or placebo for 6 mo . Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention . The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline . The uracil concentration of DNA increased in the treated group ( 5.37 fmol/microg DNA , P = 0.02 ) , whereas it did not change in the placebo group ( P = 0.42 ) . The change from baseline of 4.01 fmol uracil/microg DNA tended to differ between the groups ( P = 0.16 ) . An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group ( OR = 1.67 ; P = 0.08 ) . This study suggests that supplementation with high doses of folic acid and vitamin B-12 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas . Because such alterations may potentially increase the risk of neoplastic transformation , more research is needed to fully define the consequences of these molecular alterations We have evaluated the effect of folate supplementation ( 5 mg/day ) on global deoxyribonucleic acid ( DNA ) methylation status of the rectal mucosa of 20 patients with resected colonic adenomas in a prospect i ve , controlled , cross-over study . Baseline values of DNA methylation were inversely correlated with caloric ( P = 0.03 ) and fat intake ( P = 0.05 ) and patients harbouring multiple polyps consumed significantly more calories ( P = 0.0006 ) , fat ( P = 0.009 ) and carbohydrates ( P = 0.009 ) as compared to patients having one single lesion . Folate supplementation result ed in a significant decrease of DNA hypomethylation in 7/20 patients ( P = 0.05 ) which returned to previous values after placebo treatment . This effect was significantly correlated with number of polyps , with all the responders presenting one single lesion , whereas 8/13 of the non-responders had multiple ones ( chi2 = 7.17 , P = 0.007 ) . In conclusion , folate supplementation may decrease degree of DNA hypomethylation , but only in patients with one single polyp . In those with multiple lesions , other nutritional factors such as caloric and fat intake , may be more determinant Abstract Purpose Deficiencies of folate , vitamins B12 and D are common age-related conditions . Vitamin B12 and folate are necessary for DNA methylation . Telomeres appear to be regulated by DNA methylation . Here , we study the effect of B vitamins supplementation on telomere length and global DNA methylation in a prospect i ve study . Methods In total , 60 elderly subjects were supplemented for 1 year with either vitamin B12 , B6 , folate , vitamin D and calcium ( group A n = 31 ) or only vitamin D and calcium ( group B n = 29 ) . LINE-1 methylation , relative telomere length ( T/S ) , vitamin B12 , folate , homocysteine ( tHcy ) , 5-methyltetrahydrofolate ( 5-methylTHF ) , S-adenosylhomocysteine ( SAH ) , S-adenosylmethionine ( SAM ) , cystathionine and vitamin D were quantified before and after supplementation . Results At baseline , tHcy was high , vitamin D was low , and T/S did not differ between groups A and B. Vitamin supplementation increased LINE-1 methylation in group A at site 317 but reduced LINE-1 methylation in group B at site 327 . There was no correlation between T/S and LINE-1 methylation at baseline . Multiple backward regression analysis revealed baseline tHcy and 5-methylTHF are significant predictors of T/S. After supplementation in group B but not in group A , LINE-1 methylation correlated inversely with T/S , and LINE-1 methylation variation was an independent predictor of T/S variation . B vitamins decreased tHcy significantly in group A. Multiple backward regression analysis showed 5-methylTHF in group A and tHcy in group B were significant predictors for LINE-1 methylation . At baseline , the lower LINE-1 methylation observed in subjects with 5-methylTHF > 10 nmol/l was in agreement with a reduced methyl group transfer due to a lower SAM formation . In group B , an increase in telomere length was correlated with lower LINE-1 methylation . Subjects with hyperhomocysteinemia > 12 µmol/L had compared to those with normal tHcy a reduced LINE-1 methylation accompanied by a higher SAM and SAH ( that inhibits demethylation of SAM ) as well as lower 5-methylTHF . Additionally , subjects with tHcy > 12 µmol/L had longer telomeres when compared with subjects having tHcy < 12 µmol/L. Conclusions The results suggest a possible effect of B vitamins for telomere biology in blood cells . Suboptimal B vitamins status and hyperhomocysteinemia are associated with altered DNA methylation and telomere length . These data have to be confirmed in future studies Background Oxidative stress may lead to an increased level of unrepaired cellular DNA damage , which is discussed as one risk for tumor initiation . Mismatch repair ( MMR ) enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate . One important gene in the MMR complex is the MutL homolog 1 ( MLH1 ) gene . Since a diet rich in antioxidants has the potential to counteract harmful effects by reactive oxygen species ( ROS ) , we investigated the impact of an antioxidant , folate , and vitamin rich diet on the epigenetic pattern of MLH1 . These effects were analyzed in individuals with non-insulin depended diabetes mellitus type 2 ( NIDDM2 ) and impaired fasting glucose ( IFG ) . Methods In this post-hoc analysis of a r and omized trial we analyzed DNA methylation of MLH1 , MSH2 , and MGMT at baseline and after 8 weeks of intervention , consisting of 300 g vegetables and 25 ml plant oil rich in polyunsaturated fatty acids per day . DNA methylation was quantified using combined bisulfite restriction enzyme analysis ( COBRA ) and pyrosequencing . MLH1 and DNMT1 mRNA expression were investigated by qRT-PCR . DNA damage was assessed by COMET assay . Student ’s two-tailed paired t test and one-way ANOVA with Scheffé corrected Post hoc test was used to determine significant methylation and expression differences . Two-tailed Pearson test was used to determine correlations between methylation level , gene expression , and DNA str and break amount . Results The intervention result ed in significantly higher CpG methylation in two particular MLH1 promoter regions and the MGMT promoter . DNA str and breaks and methylation levels correlated significantly . The expression of MLH1 , DNMT1 , and the promoter methylation of MSH2 remained stable . CpG methylation levels and gene expression did not correlate . Conclusion This vitamin and antioxidant rich diet affected the CpG methylation of MLH1 . The higher methylation might be a result of the ROS scavenging antioxidant rich diet , leading to lower activity of DNA demethylating enzymes . Our results suggest the hypothesis of CpG demethylation via DNA repair enzymes under these circumstances . NIDDM2 and IFG patients benefit from this simple dietary intervention involving epigenetic and DNA repair mechanisms Low folate status increases colorectal cancer risk . Paradoxically , overly abundant folate supplementation , which is not uncommon in the United States , may increase risk . The mechanisms of these effects are unknown . We conducted two translational studies to define molecular pathways in the human colon altered either by folate supplementation or by dietary folate depletion ( followed by repletion ) . In the first study , 10 healthy , at-risk volunteers ( with documented stable/normal folate intake ) received supplemental folic acid ( 1 mg/d ) for 8 weeks . In the second study , 10 similar subjects were admitted to a hospital as in patients for 12 weeks to study folate depletion induced by a low folate diet . A repletion regimen of folic acid ( 1 mg/d ) was provided for the last 4 of these weeks . Both studies included an 8-week run-in period to ensure stabilized folate levels prior to intervention . We obtained 12 rectosigmoid biopsies ( from 4 quadrants of normal-appearing mucosa 10–15 cm from the anal verge ) at baseline and at measured intervals in both studies for assessing the primary endpoints : genome-wide gene expression , genomic DNA methylation , promoter methylation ( depletion/repletion study only ) , and p53 DNA str and breaks . Serum and rectosigmoid folate concentrations accurately tracked all changes in folate delivery ( P < 0.05 ) . In the first study , gene array analysis revealed that supplementation upregulated multiple inflammation- and immune-related pathways in addition to altering several 1-carbon – related enzymes ( P < 0.001 ) . In the second study , folate depletion downregulated genes involved in immune response , inflammation , the cell cycle , and mitochondrial/energy pathways ; repletion reversed most of these changes . However , changes in gene expression after repletion in the second study ( involving immune response and inflammation ) did not reach the levels seen after supplementation in the first study . Neither genomic nor promoter-specific DNA methylation changed during the course of the depletion/repletion protocol , and genomic methylation did not change with supplementation in the first study . p53 DNA str and breaks increased with depletion after 12 weeks . In sum , depletion downregulates , whereas repletion or supplementation upregulates pathways related to inflammation and immune response . These findings provide novel support to the concept that excessive folate supplementation might promote colorectal carcinogenesis by enhancing proinflammatory and immune response pathways . These results indicate that modest changes in folate delivery create substantial changes in the molecular milieu of the human colon . Cancer Prev Res ; 4(4 ) ; 530–43 . © 2011 AACR For the prevention of liver dysfunction in women , a choline adequate intake of 425 mg/day was established . To date , the relationship between dietary choline intake and plasma concentrations of choline moieties remains relatively unexplored . As an extension of our previous work , this 14-week controlled feeding study investigated the relationship between moderate changes in dietary choline intake and blood indicators of status . The influences of folate intake and the methylenetetrahydrofolate reductase ( MTHFR ) C677 T genotype were also considered . Healthy premenopausal women ( n=45 , 18 - 46 years ) with the MTHFR 677CC ( n=28 ) or TT ( n=17 ) genotype consumed a folate-restricted diet for 2 weeks followed by r and omization to one of four dietary treatments ( n=6 - 9/group ) differing in total choline ( 344 - 486 mg/day ) , betaine ( 122 - 349 mg/day ) and /or folate ( 400 - 800 microg dietary folate equivalents/day ) content for 12 weeks . Responses to treatment were assessed as changes in the plasma levels of choline moieties ( i.e. , betaine , choline , phosphatidylcholine and sphingomyelin ) and /or leukocyte global DNA methylation between pretreatment ( Week 2 ) and posttreatment ( Week 14 ) values . No significant changes were detected in the measured variables in response to dietary increases in choline ( i.e. , 41 % increase ) or betaine ( i.e. , 286 % increase ) intake . However , the MTHFR C677 T genotype , alone or together with a diet , influenced betaine ( P=.03 ) and phosphatidylcholine ( P=.03 ) . These data suggest that choline status is not a reliable indicator of moderate changes in dietary choline intake possibly due to the engagement of compensatory mechanisms . In addition , the MTHFR C677 T genotype appears to influence the direction and use of choline moieties in this group of women Trans-resveratrol , present in high concentration in the skin of red grapes and red wine , has a dose-dependent antiproliferative effect in vitro , prevents the formation of mammary tumors , and has been touted as a chemopreventive agent . Based upon in vitro studies demonstrating that trans-resveratrol downregulates the expression of 1 ) DNA methyltransferases and 2 ) the cancer promoting prostagl and in (PG)E2 , we determined if trans-resveratrol had a dose-related effect on DNA methylation and prostagl and in expression in humans . Thirty-nine adult women at increased breast cancer risk were r and omized in double-blind fashion to placebo , 5 or 50 mg trans-resveratrol twice daily for 12 wk . Methylation assessment of 4 cancer-related genes ( p16 , RASSF-1α , APC , CCND2 ) was performed on mammary ductoscopy specimens . The predominant resveratrol species in serum was the glucuronide metabolite . Total trans-resveratrol and glucuronide metabolite serum levels increased after consuming both trans-resveratrol doses ( P < .001 for both ) . RASSF-1α methylation decreased with increasing levels of serum trans-resveratrol ( P = .047 ) . The change in RASSF-1α methylation was directly related to the change in PGE2 ( P = .045 ) . This work provides novel insights into the effects of trans-resveratrol on the breast of women at increased breast cancer risk , including a decrease in methylation of the tumor suppressor gene RASSF-1α . Because of the limited sample size , our findings should be vali date d in a larger study OBJECTIVE Increased DNA methylation of the metabolic regulator peroxisome proliferator-activated receptor gamma coactivator 1 alpha ( PPARGC1A ) has been reported in skeletal muscle from type 2 diabetes ( T2D ) subjects and from low birth weight ( LBW ) subjects with an increased risk of T2D . High-fat overfeeding increases PPARGC1A DNA methylation in muscle in a birth weight dependent manner . However , PPARGC1A DNA methylation in subcutaneous adipose tissue ( SAT ) in LBW subjects has not previously been investigated . Our objective was to determine PPARGC1A DNA methylation and mRNA expression in basal and insulin-stimulated SAT from LBW and matched normal birth weight ( NBW ) subjects during control and high-fat overfeeding . MATERIAL S/ METHODS Nineteen young healthy men with LBW and 26 NBW controls were studied after both a 5-day high-fat overfeeding and a control diet in a r and omized crossover setting . DNA methylation was assessed with bisulfite sequencing and mRNA expression with quantitative real-time PCR . RESULTS Following high-fat overfeeding , increased SAT PPARGC1A DNA methylation was observed in LBW subjects but not in NBW controls . Basal SAT PPARGC1A mRNA expression was unaffected by diet and similar in the two groups . However , LBW subjects showed an increased SAT PPARGC1A mRNA expression during insulin-stimulation . SAT PPARGC1A methylation correlated inversely with mRNA expression during insulin-stimulation . CONCLUSIONS The study adds to the increasing awareness of PPARGC1A DNA methylation being flexible and influenced by high-fat overfeeding in a birth weight dependent manner with muscle and fat responding differently . Further data are needed to underst and the role of PPARGC1A DNA methylation in insulin resistance and developmental programming of T2D Background Studies suggest that expectations powerfully shape clinical outcomes . For subjective outcomes in adequately blinded trials , health improvements are substantial and largely explained by non-specific factors . The objective of this study was to investigate if unblinding in r and omized controlled trials ( RCTs ) is associated with enhanced placebo effects for intervention groups and nocebo effects for placebo groups . For these effects , a secondary objective was to explore potential moderating factors . Methods We included RCTs that investigated the efficacy of phosphodiesterase-5 ( PDE-5 ) inhibitors for male erectile dysfunction by comparing one PDE-5 inhibitor to placebo . In addition , to be included studies must have reported scores for change from baseline , or baseline and final International Index of Erectile Functioning-Erectile Functioning domain score ( IIEF-EF ) , and be published in either English , French , Dutch , or German . We search ed for both published and unpublished relevant trials using PUBMED , EMBASE , the Cochrane Central Register of Controlled Trials , a clinical trials register ( clinical trials.gov ) and the Food and Drug Administration clinical review s through March 2012.We evaluated the blinding status of trials with the Cochrane Risk of Bias Tool , using the domains of allocation sequence concealment , blinding of participants , healthcare providers and outcome assessors . Across these four domains , studies that scored low risk of bias were judged to be adequately blinded and studies that scored unclear or high risk of bias were judged to be inadequately blinded . Results We included 110 studies ( 205 journal publications and 2 unpublished sources ) that involved 23,877 participants ; 93 ( 85 % ) , 51 ( 46 % ) , 93 ( 85 % ) and 93 ( 85 % ) studies were assessed with an unclear risk of bias for allocation concealment , blinding of participant , blinding of caregiver and blinding of outcome assessor , respectively . None of the studies reported testing of blinding . None of the 205 journal publications provided sufficient details to assess allocation concealment , blinding of participants , caregivers and outcome assessors . After contacting authors for additional information , we judged five studies to be adequately ( n = 1,202 ) and 16 to be inadequately ( n = 3,006 ) blinded . The IIEF-EF score for placebo groups in adequately blinded trials versus inadequately blinded trials was 1.92 points ( 95 % CI , 0.64 to 3.20 ) versus 1.56 ( 95 % CI , 0.93 to 2.20 ) , respectively . The IIEF-EF score for intervention groups in adequately blinded trials versus inadequately blinded trials was 9.40 ( 95 % CI , 6.96 to 11.83 ) versus 8.33 ( 95 % CI , 7.29 to 9.37 ) , respectively . In a secondary analysis , prior experience with the drug affected the scores ; in placebo groups with participants naïve to the intervention the score was 2.89 ( 95 % CI , 2.33 to 3.45 ) versus -0.11 ( 95 % CI , -2.06 to 1.84 ) with participants having prior experience . In the intervention groups , these scores were 7.99 ( 95 % CI , 6.85 to 9.14 ) versus 8.33 ( 95 % CI , 7.51 to 9.16 ) , respectively . Unblinding lowered placebo scores ( creating a nocebo effect ) by 19 % ( 0.33 points ; 95 % CI , -0.96 to 1.62 ) . Unblinding lowered intervention scores by 11 % ( 1.0 ; 95 % CI , -1.35 to 3.47 ) . The results provided no conclusive evidence for nocebo or enhanced placebo effects . Patients taking a PDE-5 inhibitor for the first time experience a larger placebo effect that accounts for 35 % of the total effect . Conclusions Given the overall poor reporting of blinding in clinical trial reports and the small number of trials that could be rated as adequately or inadequately blinded , we could not draw any robust conclusions about the existence or absence of nocebo and enhanced placebo effects . A large placebo effect was found for patients taking PDE-5 inhibitors for the first time . It was not clear if previous exposure to the drug impacted trial blinding . We found clear evidence that studies assessing a subjective continuous outcome fail to report on measures taken to secure double blinding . Although we observed a trend for the presence of a nocebo effect , there was insufficient evidence to quantify its impact on expectations . RCTs with patients with no prior experience with PDE-5 inhibitors reported larger placebo effects and possibly these studies were better blinded . Future research should further investigate the factors that contribute to blinding and their impact on health outcomes in r and omized trials of subjectively assessed conditions . This research is part of a PhD project and has no external funding . The authors have no competing interests to declare Background Folate and its synthetic form folic acid function as donor of one-carbon units and have been , together with other B-vitamins , implicated in programming of epigenetic processes such as DNA methylation during early development . To what extent regulation of DNA methylation can be altered via B-vitamins later in life , and how this relates to health and disease , is not exactly known . The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects . This project was part of a r and omized , placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence ( B-vitamins for the PRevention Of Osteoporotic Fractures ( B-PROOF ) study ) . Participants with mildly elevated homocysteine levels , aged 65–75 years , were r and omly assigned to take 400 μg folic acid and 500 μg vitamin B12 per day or a placebo during an intervention period of 2 years . DNA was isolated from buffy coats , collected before and after intervention , and genome-wide DNA methylation was determined in 87 participants ( n = 44 folic acid/vitamin B12 , n = 43 placebo ) using the Infinium HumanMethylation450 BeadChip . Results After intervention with folic acid and vitamin B12 , 162 ( versus 14 in the placebo group ) of the 431,312 positions were differentially methylated as compared to baseline . Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo revealed one single differentially methylated position ( cg19380919 ) with a borderline statistical significance . However , based on the analyses of differentially methylated regions ( DMRs ) consisting of multiple positions , we identified 6 regions that differed statistically significantly between the intervention and placebo group . Pronounced changes were found for regions in the DIRAS3 , ARMC8 , and NODAL genes , implicated in carcinogenesis and early embryonic development . Furthermore , serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173 , 425 , and 11 regions , respectively . Interestingly , for several members of the developmental HOX genes , DNA methylation was related to serum levels of folate . Conclusions Long-term supplementation with folic acid and vitamin B12 in elderly subjects result ed in effects on DNA methylation of several genes , among which genes implicated in developmental processes This clinical trial aim ed to discover the effects of probiotic soy milk and soy milk on MLH1 and MSH2 promoter methylation , and oxidative stress among type II diabetic patients . Forty patients with type II diabetes mellitus aged 35–68 years were assigned to two groups in this r and omized , double-blind , controlled clinical trial . Patients in the intervention group consumed 200 ml/day of probiotic soy milk containing Lactobacillus plantarum A7 , while those in the control group consumed 200 ml/d of conventional soy milk for 8 weeks . Fasting blood sample s , anthropometric measurements , and 24-h dietary recalls were collected at the baseline and at the end of the study , respectively . Probiotic soy milk significantly decreased promoter methylation in proximal and distal MLH1 promoter region ( P < 0.01 and P < 0.0001 , respectively ) compared with the baseline values , while plasma concentration of 8-hydroxy-2′-deoxyguanosine ( 8-OHdG ) decreased significantly compared with soy milk ( P < 0.05 ) . In addition , a significant increase in superoxide dismutase ( SOD ) activity was observed in probiotic soy milk group compared with baseline value ( P < 0.01 ) . There were no significant changes from baseline in the promoter methylation of MSH2 within either group ( P > 0.05 ) . The consumption of probiotic soy milk improved antioxidant status in type II diabetic patients and may decrease promoter methylation among these patients , indicating that probiotic soy milk is a promising agent for diabetes management DNA methylation is a key epigenetic modification which , in mammals , occurs mainly at CpG dinucleotides . Most of the CpG methylation in the genome is found in repetitive regions , rich in dormant transposons and endogenous retroviruses . Global DNA hypomethylation , which is a common feature of several conditions such as ageing and cancer , can cause the undesirable activation of dormant repeat elements and lead to altered expression of associated genes . DNA hypomethylation can cause genomic instability and may contribute to mutations and chromosomal recombinations . Various approaches for quantification of global DNA methylation are widely used . Several of these approaches measure a surrogate for total genomic methyl cytosine and there is uncertainty about the comparability of these methods . Here we have applied 3 different approaches ( luminometric methylation assay , pyrosequencing of the methylation status of the Alu repeat element and of the LINE1 repeat element ) for estimating global DNA methylation in the same human cell and tissue sample s and have compared these estimates with the “ gold st and ard ” of methyl cytosine quantification by HPLC . Next to HPLC , the LINE1 approach shows the smallest variation between sample s , followed by Alu . Pearson correlations and Bl and -Altman analyses confirmed that global DNA methylation estimates obtained via the LINE1 approach corresponded best with HPLC-based measurements . Although , we did not find compelling evidence that the gold st and ard measurement by HPLC could be substituted with confidence by any of the surrogate assays for detecting global DNA methylation investigated here , the LINE1 assay seems likely to be an acceptable surrogate in many cases Background Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes . There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans . Methods and Results We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids ( n-3 LCPUFA ) or olive oil ( OO ) for 8 weeks on the methylation status of individual CpG loci in the 5′ regulatory region of genes involved in PUFA bio synthesis in peripheral blood mononuclear cells from men and women ( aged 53 to 63 years ) . OO and n-3 LCPUFA each altered ( > 10 % difference in methylation ) 2/22 fatty acid desaturase (FADS)-2 CpGs , while n-3 LCPUFA , but not OO , altered ( > 10 % ) 1/12 ELOVL5 CpGs in men . OO altered ( > 6 % ) 8/22 FADS2 CpGs and ( > 3 % ) 3/12 elongase (ELOVL)-5 CpGs , while n-3 LCPUFA altered ( > 5 % ) 3/22 FADS2 CpGs and 2/12 ( > 3 % ) ELOVL5 CpGs in women . FADS1 or ELOVL2 methylation was unchanged . The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults ( aged 23 to 30 years ) . The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts . Conclusions These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans , contingent on the nature of the supplement and on sex . This has implication s for underst and ing the effect of fatty acids on PUFA metabolism and cell function Epidemiologic data suggest that increasing folate intake may protect against colorectal cancer . Riboflavin may interact with folate to modulate the effect . A double-blind r and omized placebo-controlled intervention study ( the FAB2 Study ) was carried out in healthy controls and patients with colorectal polyps ( adenomatous and hyperplastic ) to examine effects of folic acid and riboflavin supplements on biomarkers of nutrient status and on putative biomarkers of colorectal cancer risk ( DNA methylation and DNA damage ; to be reported elsewhere ) . Ninety-eight healthy controls and 106 patients with colorectal polyps were stratified for the thermolabile variant of methylene tetrahydrofolate reductase , MTHFR C677 T , and were r and omized to receive 400 μg of folic acid , 1,200 μg of folic acid , or 400 μg of folic acid plus 5 mg of riboflavin or placebo for 6 to 8 weeks . Blood sample s and colon biopsy sample s were collected for the measurement of biomarkers of folate and riboflavin status . Supplementation with folic acid elicited a significant increase in mucosal 5-methyl tetrahydrofolate , and a marked increase in RBC and plasma , with a dose-response . Measures of riboflavin status improved in response to riboflavin supplementation . Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps . The magnitude of the response in mucosal folate was positively related to the increase in plasma 5-methyl tetrahydrofolate but was not different between the healthy group and polyp patients . Colorectal mucosal folate concentration responds to folic acid supplementation to an extent comparable to that seen in plasma , but with a suggestion of an upper limit . ( Cancer Epidemiol Biomarkers Prev 2007;16(10):2128–35 We determined if soy isoflavones have dose-related estrogenic and methylation effects . Thirty-four healthy premenopausal women were r and omized to 40 mg or 140 mg isoflavones daily through one menstrual cycle . Breast specific and systemic estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology , whereas methylation assessment of 5 cancer related genes ( p16 , RASSF1A , RAR β 2 , ER , and CCND2 ) was performed on intraductal specimens . Serum genistein significantly increased after consuming both isoflavone doses . Cytology did not significantly change at either isoflavone dose . Serum C3 levels posttreatment were inversely related to change in serum genistein ( r = –0.76 , P = 0.0045 ) in women consuming low but not high dose isoflavones . The RAR β 2 hypermethylation increase posttreatment correlated with the posttreatment genistein level considering the entire group ( r = 0.67 , P = 0.0017 ) and those receiving high-dose isoflavones ( r = 0.68 , P = 0.021 ) . At the low but not the high isoflavone dose , CCND2 hypermethylation increase correlated with posttreatment genistein levels ( r = 0.79 , P = 0.011 ) . In summary , the inverse correlation between C3 and genistein suggests an antiestrogenic effect . Isoflavones induced dose-specific changes in RAR β 2 and CCND2 gene methylation , which correlated with genistein levels . This work provides novel insights into estrogenic and methylation effects of dietary isoflavones BACKGROUND Hyperhomocysteinaemia occurs in several genetically determined and acquired disorders and is highly prevalent in patients with uraemia . In these disorders , homocysteine precursor S-adenosylhomocysteine , a powerful competitive inhibitor of S-adenosylmethionine-dependent methyltransferases , is increased , suggesting unbalanced methylation . We aim ed to investigate whether DNA hypomethylation is present in patients with uraemia who also have hyperhomocysteinaemia and whether regulation of specific classes of genes , dependent on DNA methylation , is compromised . METHODS We selected men with hyperhomocysteinaemia and uraemia who were having st and ard haemodialysis treatment , and compared them with healthy male controls . We measured the homocysteine concentration from plasma sample s and obtained DNA and RNA sample s from peripheral mononuclear cells . DNA methylation was assessed by cytosine extension assay and by Southern blotting . Allelic expression of pseudoautosomal and imprinted genes was investigated by analysis of suitable restriction fragment length polymorphisms . FINDINGS Total DNA hypomethylation was higher in patients than in controls ( z score -4.593 , p=0.0006 ) and allelic expression was changed in both sex-linked and imprinted genes . The shift from monoallelic to biallelic expression was dependent on homocysteine concentrations . Folate therapy , a common method to reduce hyperhomocysteinaemia , restored DNA methylation to normal levels and corrected the patterns of gene expression . INTERPRETATION Our results suggest that hyperhomocysteinaemia affects epigenetic control of gene expression , which can be reverted by folate treatment . Our data support the hypothesis that the toxic action of homocysteine can be mediated by macromolecule hypomethylation Aims /hypothesisEnergy-dense diets that are high in fat are associated with a risk of metabolic diseases . The underlying molecular mechanisms could involve epigenetics , as recent data show altered DNA methylation of putative type 2 diabetes c and i date genes in response to high-fat diets . We examined the effect of a short-term high-fat overfeeding ( HFO ) diet on genome-wide DNA methylation patterns in human skeletal muscle . Methods Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet , in a r and omised crossover setting . DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina 's Infinium Bead Array . C and i date gene expression was determined by quantitative real-time PCR . Results HFO introduced widespread DNA methylation changes affecting 6,508 genes ( 45 % ) , with a maximum methylation change of 13.0 percentage points . The HFO-induced methylation changes were only partly and non-significantly reversed after 6–8 weeks . Alterations in DNA methylation levels primarily affected genes involved in inflammation , the reproductive system and cancer . Few gene expression changes were observed and these had poor correlation to DNA methylation . Conclusions /interpretationThe genome-wide DNA methylation changes induced by the short-term HFO diet could have implication s for our underst and ing of transient epigenetic regulation in humans and its contribution to the development of metabolic diseases . The slow reversibility suggests a methylation build-up with HFO , which over time may influence gene expression levels Abstract Background : Disturbed DNA methylation is causally related to chronic diseases like cancer and atherosclerosis . B vitamins are cofactors required for methyl group synthesis and may therefore affect DNA methylation . Vitamin D has epigenetic effects . We tested if B and D vitamin supplementation has an effect on genomic long interspersed nuclear element-1 ( LINE-1 ) methylation and the metabolites S-adenosylmethionine ( SAM ) and S-adenosylhomocysteine ( SAH ) . Methods : Fifty subjects ( median age 68.0 years ) were supplemented with a daily oral dose of B vitamins ( 500 µg folic acid , 500 µg vitamin B12 and 50 mg vitamin B6 ) , 1200 IU vitamin D and 456 mg calcium . Fasting blood sample s were collected before and after 1 year of supplementation . LINE-1 methylation was determined in genomic DNA from blood cells as a surrogate for whole genome methylation . In addition , SAM , SAH and total homocysteine ( tHcy ) were measured in plasma sample s. Results : Plasma homocysteine decreased significantly after supplementation ( 12.8 vs. 9.1 µmol/L ; p<0.05 ) , whereas SAM , SAH , the SAM/SAH ratio and LINE-1 methylation did not change significantly . LINE-1 methylation was not significantly correlated with SAH , homocysteine or B vitamins . Conclusions : Long-term vitamin B supplementation had no effect on LINE-1 methylation in blood cells nor on plasma levels of SAM and SAH . Vitamin B and D supplementation seems to have no effect on DNA methylation , especially in cases where no severe deficiency exists OBJECTIVES Obesity and weight-loss are associated with methylation patterns in specific genes , but their effect on Long Interspersed Nuclear Elements ( LINE-1 ) methylation , a measure of global methylation is largely unknown . METHODS Three hundred overweight/obese post-menopausal women ( 50 - 75 years ) were part of a completed , 1-year r and omized controlled trial , comparing independent and combined effects of a reduced-calorie weight-loss diet , and exercise program , versus control . DNA was extracted from peripheral blood leukocytes collected at baseline and 12-months , and LINE-1 methylation analyzed by pyrosequencing . Mean changes between groups using generalized estimating equations and examined effects of weight-loss on LINE-1 methylation using stratified analyses ( gained weight/no weight-loss [ N = 84 ] ; < 5 % [ N = 45 ] ; 5%-10 % [ N = 45 ] ; > 10 % of baseline weight-loss [ N = 126 ] ) within each arm , adjusted by blood cell counts were compared . Associations between LINE-1 methylation and previously measured biomarkers , and anthropometrics were also examined . RESULTS No significant difference in LINE-1 methylation levels was detected in any intervention group versus controls . The magnitude of weight-loss was not associated with LINE-1 methylation at 12-months . There were no associations between baseline characteristics of participants , or previously measured biomarkers , and LINE-1 methylation . CONCLUSIONS Our results suggest that lifestyle changes sufficient to significantly reduce weight over 12-months may not change LINE-1 DNA methylation levels Background : Global loss of methylated cytosines in DNA , thought to predispose to chromosomal instability and aneuploidy , has been associated with an increased risk of colorectal neoplasia . Little is known about the relationships between global hypomethylation and lifestyle , demographics , dietary measures , and genetic factors . Methods : Our data were collected as part of a r and omized clinical trial testing the efficacy of aspirin and folic acid for the prevention of colorectal adenomas . At a surveillance colonoscopy ∼3 years after the qualifying exam , we obtained two biopsies of the normal-appearing mucosa from the right colon and two biopsies from the left colon . Specimens were assayed for global hypomethylation using a pyrosequencing assay for LINE-1 ( long interspersed nucleotide elements ) repeats . Results : The analysis included data from 388 subjects . There was relatively little variability in LINE methylation overall . Mean LINE-1 methylation levels in normal mucosa from the right bowel were significantly lower than those on the left side ( P < 0.0001 ) . No significant associations were found between LINE-1 methylation and folate treatment , age , sex , body mass index , smoking status , alcohol use , dietary intake , or circulating levels of B vitamins , homocysteine , or selected genotypes . Race , dietary folic acid , and plasma B6 showed associations with global methylation that differed between the right and the left bowel . The effect of folic acid on risk of adenomas did not differ according to extent of LINE-1 methylation , and we found no association between LINE-1 methylation and risk of adenomas . Conclusions : LINE-1 methylation is not influenced by folic acid supplementation but differs by colon subsite . ( Cancer Epidemiol Biomarkers Prev 2009;18(4):1041–9 Aims /hypothesisThe association between low birthweight ( LBW ) and risk of developing type 2 diabetes may involve epigenetic mechanisms , with skeletal muscle being a prime target tissue . Differential DNA methylation patterns have been observed in single genes in muscle tissue from type 2 diabetic and LBW individuals , and we recently showed multiple DNA methylation changes during short-term high-fat overfeeding in muscle of healthy people . In a r and omised crossover study , we analysed genome-wide DNA promoter methylation in skeletal muscle of 17 young LBW men and 23 matched normal birthweight ( NBW ) men after a control and a 5 day high-fat overfeeding diet . Methods DNA methylation was measured using Illumina ’s Infinium BeadArray covering 27,578 CpG sites representing 14,475 different genes . Results After correction for multiple comparisons , DNA methylation levels were found to be similar in the LBW and NBW groups during the control diet . Whereas widespread DNA methylation changes were observed in the NBW group in response to high-fat overfeeding , only a few methylation changes were seen in the LBW group ( χ2 , p < 0.001 ) . Conclusions /interpretationOur results indicate lower DNA methylation plasticity in skeletal muscle from LBW vs NBW men , potentially contributing to underst and ing the link between LBW and increased risk of type 2 diabetes Several studies have suggested that DNA hypomethylation is an early step in colorectal carcinogenesis . However , it is not clear at which stage in carcinogenesis this hypomethylation occurs , what promotes it , the extent to which it can be reversed and the consequences of such reversal in affecting tumour development . In an attempt to address some of these questions , we studied three groups of subjects with similar age and gender distributions : a group of 12 patients with colorectal carcinomas ; a group of 12 patients with colorectal adenomas ; and a group of eight healthy control subjects . Two experimental protocol s were employed . In the first protocol , intrinsic DNA methylation was evaluated in neoplastic and in normal-appearing rectal mucosa of patients with colonic carcinomas or adenomas , compared with a group of healthy controls . In the second protocol , we examined , in a prospect i ve and controlled fashion , the effect of folic acid supplementation ( 10 mg/day ) on the degree of DNA methylation of rectal mucosa from those same patients after removal of the neoplasms . The degree of intrinsic DNA methylation was assessed on the basis of the capacity of the DNA isolates to serve as methyl acceptors in in vitro incubations that contained DNA methylase and [ 3H-methyl ] S-adenosylmethionine . Intrinsic DNA methylation was significantly lower in carcinomas than in adenomas ( P < 0.005 ) . In addition , normal-appearing rectal mucosa from patients with carcinomas was significantly less methylated than in healthy controls ( P < 0.005 ) ; the mean value found in the latter was also greater than the value observed in patients with adenomas , but not significantly so ( P > 0.05 ) . Patients with resected neoplasms who received folk acid supplementation for 6 months had a marked increase in the degree of intrinsic DNA methylation in the rectal mucosa ( P < 0.002 ) . Three months after cessation of treatment , DNA methylation decreased substantially ( P < 0.05 ) , but remained significantly greater than baseline values ( P < 0.02 ) . In contrast , DNA methylation values remained stable throughout the study in placebo-treated patients ( P = 0.40 ) . Our study demonstrates that global DNA hypomethylation occurs in normal rectal mucosa from patients with colorectal neoplasms as compared with controls , and that it was significantly reduced with pharmacological doses of folk add . It remains to be determined whether the risk of tumour recurrence is affected as well Familial adenomatous polyposis ( FAP ) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer . FAP is treated by colectomy followed by lifelong removal of rectal polyps . This study determined whether black raspberries ( BRBs ) might regress rectal polyps in patients with FAP . Fourteen patients with FAP were treated with BRBs daily for 9 months . Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime . The other 7 received an oral placebo plus the suppositories . Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment . Polyps and adjacent normal tissue were collected at both time points . The burden ( P = 0.036 ) but not number ( P = 0.069 ) of rectal polyps was significantly decreased . No benefit was noted with the addition of oral BRBs . Three patients were nonresponders . BRBs significantly decreased cellular proliferation , DNA methylation methyl transferase 1 protein expression , and p16 promoter methylation , but not promoter methylation of the Wnt pathway antagonists , SFRP2 and WIF1 , in rectal polyps ( adenomas ) from responders but not from nonresponders . The MBD-seq assay revealed more demethylated transcription start sites ( TSS ) , including those for miRNAs , in BRB-treated adenomas from the responders . In conclusion , BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP . Cancer Prev Res ; 7(7 ) ; 666–74 . © 2014 AACR Changes in DNA methylation patterns are a hallmark of tobacco-induced carcinogenesis . We have conducted a r and omized 4-week intervention trial to investigate the effects of three dietary regimens to modify DNA methylation patterns in peripheral white blood cells of heavy smokers . A group of 88 smokers were r and omly assigned to and distributed among three diets , including ( 1 ) normal isocaloric diet ( balanced in fruits and vegetables ) , according to international guidelines ; ( 2 ) a diet enriched in flavonoids and isothiocyanates ( particularly cruciferous vegetables ) ; ( 3 ) a regimen consisting of diet 1 supplemented with flavonoids ( green tea and soy products ) . Methylation patterns were analyzed by pyrosequencing in LINE1 ( Long Interspersed DNA Elements ) , RASSF1A , ARF and CDKN2a ( tumor suppressor genes ) , MLH1 ( mismatch DNA repair ) and MTHFR ( folate metabolism ) . Three distinct patterns of methylation were observed . In LINE1 , methylation showed a small but reproducible increase with all three regimens . MTHFR was constitutively methylated with no significant modulation by diets . The four other loci showed low basal levels of methylation with no substantial change after intervention . These data suggest that the isocaloric diet may stabilize global epigenetic ( LINE1 DNA methylation ) patterns in peripheral white blood cells but does not provide evidence for methylation changes in specific genes associated with this short-term dietary intervention BACKGROUND Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure . Among other uraemic toxins , homocysteine ( Hcy ) levels are increased in most of these patients . In healthy individuals , plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes ( PBL ) . The accumulation of Hcy can be reduced by supplementation with folic acid and vitamin B12 . The aim of this study was to analyse whether this supplementation can also lower the genomic damage in PBL of haemodialysis patients . This may ultimately help to reduce cancer incidence in renal patients . METHODS In a prospect i ve study with 27 patients , we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation . Genomic damage was measured by the frequency of micronuclei , a subset of chromosomal aberrations , in PBL . RESULTS Supplementation with folic acid and vitamin B12 ( more markedly with both ) reduced the micronucleus frequency in PBL of dialysis patients . This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation . Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation , and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N(6)-etheno-2'-deoxyadenosine , a marker for oxidative stress . CONCLUSIONS A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12 . This may be mediated by Hcy reduction Objective : Folic acid ( FA ) supplementation decreases homocysteine ( tHcy ) levels . However , little is known about the effects of FA treatment on DNA methylation or plasma S-adenosylmethionine ( AdoMet ) and S-adenosylhomocysteine ( AdoHcy ) concentrations . The purpose of this study was to investigate the effects of FA supplementation on AdoMet , AdoHcy , and genomic DNA methylation in hyperhomocysteinemic subjects without end-stage renal disease . Methods : To evaluate the effects of 5 mg FA/d for 8 weeks , we recruited 7 hyperhomocysteinemic MTHFR677TT patients ( tHcy > 30 μmol/L ) with normal renal function . Results : FA supplementation induced a decrease in tHcy ( from 51.1 ± 21 at baseline to 26.1 ± 27 μmol/L after folate supplementation ; p < 0.01 ) . A parallel increase was seen in plasma AdoMet concentrations and the AdoMet/AdoHcy ratio ( p < 0.05 ) . However , FA supplementation had no effect on global DNA methylation levels in the present study . Conclusions : Supraphysiologic FA supplementation can modulate biochemical markers in one-carbon metabolism such as tHcy , AdoMet , and the AdoMet/AdoHcy ratio in hyperhomocysteinemic subjects . However , the reduction in homocysteinemia and the increased availability of methyl compounds provided by vitamin supplementation may not be sufficient to affect genomic DNA methylation Dietary factors modulate gene expression and are able to alter epigenetic signatures in peripheral blood mononuclear cells ( P BMC ) . However , there are limited studies about the effects of omega-3 polyunsaturated fatty acids ( n-3 PUFA ) on the epigenetic mechanisms that regulate gene expression . This research investigates the effects of n-3-rich fish oil supplementation on DNA methylation profile of several genes whose expression has been reported to be downregulated by n-3 PUFA in P BMC : CD36 , FFAR3 , CD14 , PDK4 , and FADS1 . Young overweight women were supplemented with fish oil or control in a r and omized 8-week intervention trial following a balanced diet with 30 % energy restriction . Fatty acid receptor CD36 decreased DNA methylation at CpG + 477 due to energy restriction . Hypocaloric diet-induced weight loss also reduced the methylation percentages of CpG sites located in CD14 , PDK4 , and FADS1 . The methylation patterns of these genes were only slightly affected by the fish oil supplementation , being the most relevant to the attenuation of the weight loss-induced decrease in CD36 methylation after adjusting by baseline body weight . These results suggest that the n-3 PUFA-induced changes in the expression of these genes in P BMC are not mediated by DNA methylation , although other epigenetic mechanisms can not be discarded Background : Dietary fat composition can affect ectopic lipid accumulation and , thereby , insulin resistance . Diets that are high in saturated fatty acids ( SFAs ) or polyunsaturated fatty acids ( PUFAs ) have different metabolic responses . Objective : We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a r and omized trial . Design : We studied the effects of 7 wk of excessive SFA ( n = 17 ) or PUFA ( n = 14 ) intake ( + 750 kcal/d ) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue . Both diets result ed in similar body weight increases . We also combined the data from the 2 groups to examine the overall effect of overfeeding on the DNA methylation in adipose tissue . Results : The DNA methylation of 4875 Cytosine-phosphate-guanine ( CpG ) sites was affected differently between the 2 diets . Furthermore , both the SFA and PUFA diets increased the mean degree of DNA methylation in adipose tissue , particularly in promoter regions . However , although the mean methylation was changed in 1797 genes [ e.g. , alpha-ketoglutarate dependent dioxygenase ( FTO ) , interleukin 6 ( IL6 ) , insulin receptor ( INSR ) , neuronal growth regulator 1 ( NEGR1 ) , and proopiomelanocortin ( POMC ) ] by PUFAs , only 125 genes [ e.g. , adiponectin , C1Q and collagen domain containing ( ADIPOQ ) ] were changed by SFA overfeeding . In addition , the SFA diet significantly altered the expression of 28 transcripts [ e.g. , acyl-CoA oxidase 1 ( ACOX1 ) and FAT atypical cadherin 1 ( FAT1 ) ] , whereas the PUFA diet did not significantly affect gene expression . When the data from the 2 diet groups were combined , the mean methylation of 1444 genes , including fatty acid binding protein 1 ( FABP1 ) , fatty acid binding protein 2 ( FABP2 ) , melanocortin 2 receptor ( MC2R ) , MC3R , PPARG coactivator 1 α ( PPARGC1A ) , and tumor necrosis factor ( TNF ) , was changed in adipose tissue by overfeeding . Moreover , the baseline DNA methylation of 12 CpG sites that was annotated to 9 genes [ e.g. , mitogen-activated protein kinase 7 ( MAPK7 ) , melanin concentrating hormone receptor 1 ( MCHR1 ) , and splicing factor SWAP homolog ( SFRS8 ) ] was associated with the degree of weight increase in response to extra energy intake . Conclusions : SFA overfeeding and PUFA overfeeding induce distinct epigenetic changes in human adipose tissue . In addition , we present data that suggest that baseline DNA methylation can predict weight increase in response to overfeeding in humans . This trial was registered at clinical trials.gov as NCT01427140 OBJECTIVES : Dietary folate intake is inversely associated with the risk of colorectal cancer . This study investigated the effect of folate supplementation on genomic DNA methylation and DNA str and breaks in exons 5–8 of the p53 gene of the colonic mucosa , two provisional biomarkers of colon cancer . METHODS : Twenty subjects with adenomas were r and omized to receive either folate ( 5 mg/day ) or placebo for 1 yr after polypectomy . At baseline , 6 months and 1 yr , systemic and colonic measures of folate status were determined , as were the biomarkers mentioned earlier . RESULTS : Folate supplementation increased serum , red blood cell and colonic mucosal folate concentrations ( p < 0.02 ) . Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr ( p = 0.001 ) , whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr . Similarly , folate supplementation decreased the extent of p53 str and breaks in exons 5–8 at 6 months and 1 yr ( p < 0.02 ) , whereas placebo administration was associated with a decrease in the extent of p53 str and breaks only at 1 yr . CONCLUSIONS : Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation . However , these markers also improved with placebo at 1 yr . Therefore , potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials SCOPE Epigenetic processes may be affected by environmental factors . DNA methylation measured in LINE-1 elements ( LINE-1 , long interspersed nucleotide element-1 ) correlates with LINE-1 DNA methylation . Variations in stearoyl CoA desaturase ( SCD ) activity ( a key enzyme in the fatty acid metabolism ) may be involved in various processes that can lead to diseases such as obesity . We evaluated whether changes in diet after a nutritional intervention would be associated with changes in LINE-1 DNA methylation and /or specific methylation of SCD1 gene promoter . METHODS AND RESULTS DESIGN Prospect i ve cohort intervention study with a control group . We recorded phenotypic , anthropometric , biochemical , and nutritional information at baseline and 1 year later . DNA methylation was quantified by pyrosequencing . LINE-1 DNA methylation and SCD1 gene promoter methylation levels were similar at the beginning of the study in both population s , whereas after a year these levels were higher in the control group ( p < 0.001 ) . In the intervention group , those subjects who lost weight showed higher levels of SCD1 gene promoter methylation after the intervention . Subjects with lower adherence to a Mediterranean diet experienced larger changes in LINE-1 methylation . CONCLUSION DNA methylation levels were associated with weight change and with adherence to a Mediterranean diet CONTEXT Low birth weight ( LBW ) and unhealthy diets are risk factors of metabolic disease including type 2 diabetes ( T2D ) . Genetic , nongenetic , and epigenetic data propose a role of the key metabolic regulator peroxisome proliferator-activated receptor gamma , coactivator 1alpha ( PPARGC1A ) in the development of T2D . OBJECTIVE Our objective was to investigate gene expression and DNA methylation of PPARGC1A and coregulated oxidative phosphorylation ( OXPHOS ) genes in LBW and normal birth weight ( NBW ) subjects during control and high-fat diets . DESIGN , SUBJECTS , AND MAIN OUTCOME MEASURES : Twenty young healthy men with LBW and 26 matched NBW controls were studied after 5 d high-fat overfeeding ( + 50 % calories ) and after a control diet in a r and omized manner . Hyperinsulinemic-euglycemic clamps were performed and skeletal muscle biopsies excised . DNA methylation and gene expression were measured using bisulfite sequencing and quantitative real-time PCR , respectively . RESULTS When challenged with high-fat overfeeding , LBW subjects developed peripheral insulin resistance and reduced PPARGC1A and OXPHOS ( P < 0.05 ) gene expression . PPARGC1A methylation was significantly higher in LBW subjects ( P = 0.0002 ) during the control diet . However , PPARGC1A methylation increased in only NBW subjects after overfeeding in a reversible manner . DNA methylation of PPARGC1A did not correlate with mRNA expression . CONCLUSIONS LBW subjects developed peripheral insulin resistance and decreased gene expression of PPARGC1A and OXPHOS genes when challenged with fat overfeeding . The extent to which our finding of a constitutively increased DNA methylation in the PPARGC1A promoter in LBW subjects may contribute needs to be determined . We provide the first experimental support in humans that DNA methylation induced by overfeeding is reversible BACKGROUND Low folate status is associated with an increased risk of colorectal carcinogenesis . Optimal folate status may be genoprotective by preventing uracil misincorporation into DNA and DNA hypomethylation . Adenomatous polyps have low folate status compared with normal colonic mucosa , and they are surrounded by histologically normal mucosa that also is of low folate status . OBJECTIVE In a r and omized controlled trial conducted at a single Dublin hospital between April 2002 and March 2004 , we assessed the effect of folic acid supplementation on tissue folate , uracil misincorporation into DNA , and global DNA hypomethylation in colonocytes isolated from sites of adenomatous polyps and from histologically normal tissue adjacent and 10 - 15 cm distal to them . METHODS Twenty patients with adenomatous polyps on initial colonoscopy and polypectomy were r and omly assigned to receive either 600 μg folic acid/d [ n = 12 , 38 % men , mean age 64.3 y , and body mass index ( BMI , in kg/m(2 ) ) 26.6 ] or placebo ( n = 8 , 50 % men , mean age 68.4 y , and BMI 27.2 ) for 6 mo , and then repeat the colonoscopy . Blood and colonocyte tissue folate concentrations were measured with the use of a microbiological assay . Uracil misincorporation and global DNA hypomethylation were measured in colonocytes with the use of modified comet assays . RESULTS Over time , folic acid supplementation , compared with placebo , increased tissue folate ( mean ± SEM ) from 15.6 ± 2.62 pg/10(5 ) cells to 18.1 ± 2.12 pg/10(5 ) cells ( P < 0.001 ) and decreased the global DNA hypomethylation ratio from 1.7 ± 0.1 to 1.0 ± 0.1 ( P < 0.001 ) . The uracil misincorporation ratio decreased by 0.5 ± 0.1 for the site adjacent to the polyp over time ( P = 0.05 ) . CONCLUSION A response to folic acid supplementation , which increased colonocyte folate and improved folate-related DNA biomarkers of cancer risk , was seen in the participants studied . Exploratory analysis points toward the area formerly adjacent to polyps as possibly driving the response . That these areas persist after polypectomy in the absence of folate supplementation is consistent with a potentially carcinogenic field 's causing the appearance of the polyp Epigenetic processes , including DNA methylation , might be modulated by environmental factors such as the diet , which in turn have been associated with the onset of several diseases such as obesity or cardiovascular events . Meanwhile , Mediterranean diet ( MedDiet ) has demonstrated favourable effects on cardiovascular risk , blood pressure , inflammation and other complications related to excessive adiposity . Some of these effects could be mediated by epigenetic modifications . Therefore , the objective of this study was to investigate whether the adherence to MedDiet is associated with changes in the methylation status from peripheral blood cells . A subset of 36 individuals was selected within the Prevención con Dieta Mediterránea (PREDIMED)-Navarra study , a r and omised , controlled , parallel trial with three groups of intervention in high cardiovascular risk volunteers , two with a MedDiet and one low-fat control group . Changes in methylation between baseline and 5 years were studied . DNA methylation arrays were analysed by several robust statistical tests and functional classifications . Eight genes related to inflammation and immunocompetence ( EEF2 , COL18A1 , IL4I1 , LEPR , PLAGL1 , IFRD1 , MAPKAPK2 , PPARGC1B ) were finally selected as changes in their methylation levels correlated with adherence to MedDiet and because they presented sensitivity related to a high variability in methylation changes . Additionally , EEF2 methylation levels positively correlated with concentrations of TNF-α and CRP . This report is apparently the first showing that adherence to MedDiet is associated with the methylation of the reported genes related to inflammation with a potential regulatory impact |
2,176 | 30,462,793 | Cupping therapy has shown positive results on chronic back pain .
There is no st and ardization in the treatment protocol .
The main assessed outcomes were pain intensity , physical incapacity , quality of life and nociceptive threshold before the mechanical stimulus .
cupping therapy is a promising method for the treatment of chronic back pain in adults . | OBJECTIVES to evaluate the evidence from the literature regarding the effects of cupping therapy on chronic back pain in adults , the most used outcomes to evaluate this condition , the protocol used to apply the intervention and to investigate the effectiveness of cupping therapy on the intensity of chronic back pain . | OBJECTIVES This was a r and omized controlled pilot trial to evaluate the effectiveness of cupping therapy for neck pain in video display terminal ( VDT ) workers . METHODS Forty VDT workers with moderate to severe neck pain were recruited from May , 2011 to February , 2012 . Participants were r and omly allocated into one of the two interventions : 6 sessions of wet and dry cupping or heating pad application . The participants were offered an exercise program to perform during the participation period . A 0 to 100 numeric rating scale ( NRS ) for neck pain , measure yourself medical outcome profile 2 score ( MYMOP2 score ) , cervical spine range of motion ( C-spine ROM ) , neck disability index ( NDI ) , the EuroQol health index ( EQ-5D ) , short form stress response inventory ( SRI-SF ) and fatigue severity scale ( FSS ) were assessed at several points during a 7-week period . RESULTS Compared with a heating pad , cupping was more effective in improving pain ( adjusted NRS difference : -1.29 [ 95 % CI -1.61 , -0.97 ] at 3 weeks ( p=0.025 ) and -1.16 [ -1.48 , -0.84 ] at 7 weeks ( p=0.005 ) ) , neck function ( adjusted NDI difference : -0.79 [ -1.11 , -0.47 ] at 3 ( p=0.0039 ) and 7 weeks ( p<0.0001 ) ) and discomfort ( adjusted MYMOP2 difference score : -0.72 [ -1.04 to -0.40 ] at 3 weeks and -0.92 [ -1.24 , -0.60 ] at 7 weeks ) . Significant improvement in EQ-5D was observed at 7 weeks ( 1.0 [ 0.88 , 1.0 ] with cupping and 0.91 [ 0.86 , 0.91 ] with heating pad treatment , p=0.0054 ) . Four participants reported mild adverse events of cupping . CONCLUSION Two weeks of cupping therapy and an exercise program may be effective in reducing pain and improving neck function in VDT workers Introduction . Cupping has been used since antiquity in the treatment of pain conditions . In this pilot study , we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain ( CNP ) and mechanical sensory thresholds . Methods . Fifty CNP patients were r and omly assigned to treatment ( TG , n = 25 ) or waiting list control group ( WL , n = 25 ) . TG received a single cupping treatment . Pain at rest ( PR ) , pain related to movement ( PM ) , quality of life ( SF-36 ) , Neck Disability Index ( NDI ) , mechanical detection ( MDT ) , vibration detection ( MDT ) , and pressure pain thresholds ( PPT ) were measured before and three days after a single cupping treatment . Patients also kept a pain and medication diary ( PaDi , MeDi ) during the study . Results . Baseline characteristics were similar in the two groups . After cupping TG reported significantly less pain ( PR : −17.9 mm VAS , 95%CI −29.2 to −6.6 ; PM : −19.7 , 95%CI −32.2 to −7.2 ; PaDi : −1.5 points on NRS , 95%CI −2.5 to −0.4 ; all P < 0.05 ) and higher quality of life than WL ( SF-36 , Physical Functioning : 7.5 , 95%CI 1.4 to 13.5 ; Bodily Pain : 14.9 , 95%CI 4.4 to 25.4 ; Physical Component Score : 5.0 , 95%CI 1.4 to 8.5 ; all P < 0.05 ) . No significant effect was found for NDI , MDT , or VDT , but TG showed significantly higher PPT at pain- areas than WL ( in lg(kPa ) ; pain-maximum : 0.088 , 95%CI 0.029 to 0.148 , pain-adjacent : 0.118 , 95%CI 0.038 to 0.199 ; both P < 0.01 ) . Conclusion . A single application of traditional cupping might be an effective treatment for improving pain , quality of life , and hyperalgesia in CNP Abstract Objectives : To evaluate the effectiveness and safety of wet cupping therapy as a single treatment for persistent nonspecific low back pain ( PNSLBP ) . Design : R and omized controlled trial comparing wet cupping versus no treatment in PNSLBP . Setting : Outpatient clinic in three secondary care hospitals in Saudi Arabia . Patients : Eighty eligible participants with PNSLBP for at least 3 months were r and omly allocated to an intervention group ( n=40 ) or to a control group ( n=40 ) . Interventions : Six wet cupping sessions within 2 weeks , each of which were done at two bladder meridian ( BL ) acupuncture points among BL23 , BL24 , and BL25 . Only acetaminophen was allowed as a rescue treatment in both groups . Outcome measures : The Numeric Rating Scale ( NRS ) , McGill Present Pain Intensity ( PPI ) , and Oswestry Disability Question naire ( ODQ ) were used as outcome measures . Numbers of acetaminophen tablets taken were compared at 4 weeks from baseline . Adverse events were recorded . Results : At the end of the intervention , statistically significant differences in the three outcome measures favoring the wet cupping group compared with the control group were seen : NRS score , 29.2 ( 95 % confidence interval [ CI ] , 24.6–33.8 ) versus 57.9 ( 95 % CI , 53.3–62.6 ) , respectively ; PPI score , 1.17 ( 95 % CI , 0.96–1.4 ) versus 2.3 ( 95 % CI , 2.1– 2.7 ) ; and ODQ score , 19.6 ( 95 % CI , 16.5–22.7 ) versus 35.4 ( 95 % CI , 32.3–38.5 ) ( p=0.0001 ) . This improvement continued for another 2 weeks after the end of the intervention . Acetaminophen was used less in the wet cupping group , but this difference was not statistically significant . No adverse events were reported . Conclusions : Wet cupping is potentially effective in reducing pain and improving disability associated with PNSLBP at least for 2 weeks after the end of the wet cupping period . Placebo-controlled trials are needed The purpose of this study was to evaluate the effect of laser acupuncture ( LA ) and soft cupping on low back pain . In this study , the subjects were r and omly assigned to two groups : active group ( real LA and soft cupping ) and placebo group ( sham laser and soft cupping ) . Visual analog scale ( VAS ) and Ryodoraku were used to evaluate the effect of treatment on low back pain in this trial . Laser , 40 mW , wavelength 808 nm , pulse rate 20 Hz , was used to irradiate Weizhong ( BL40 ) and Ashi acupoints for 10 minutes . And the Ryodoraku values were measured 2 times , that is , before and 15 minutes after treatment . The results show that there were significant difference between the first day baseline and the fifth day treatment in VAS in the two groups . Therefore , LA combined with soft cupping or only soft cupping was effective on low back pain . However , the Ryodoraku values of Bladder Meridian of the placebo group have been decreased apparently , and did n't come back to their original values . It means that “ cupping ” plays the role of “ leak or purge ” in traditional Chinese medicine ( TCM ) . On the other h and , the Ryodoraku values of Bladder Meridian of the active group have been turned back to almost their original values ; “ mend or reinforcing ” effect is attributed to the laser radiation Background : Chronic neck pain is a major public health burden with only limited evidence for the effectiveness of complementary therapies . This study aim ed to test the efficacy of cupping massage in patients with neck pain . Patients and Methods : Patients with chronic non-specific neck pain were r and omly assigned to cupping massage or a wait list control . The intervention group received 5 cupping massages on a twice-weekly basis while the control patients continued their usual treatments . The primary outcome measure was neck pain intensity ( 0 - 100 mm visual analogue scale ( VAS ) ) after 3 weeks . Secondary outcomes included pain on movement , functional disability , health-related quality of life , mechanical detection and pain thresholds and adverse events . Results : 50 patients ( 52.6 ± 10.3 years , 92 % female ) were r and omised to either cupping massage or a wait list ( N = 25 each ) . Patients in the cupping group reported significantly less neck pain post intervention ( difference per protocol -14.3 mm , 95 % confidence interval ( CI ) -27.7 to -1.0 , p = 0.037 ; difference intention-to-treat -10.8 mm , 95 % CI -21.5 to -0.1 , p = 0.047 ) . Significant group differences in favour of the intervention were further found for pain on movement ( p = 0.019 ) and functional disability ( p < 0.001 ) , the quality -of-life subscales pain ( p = 0.002 ) and mental health ( p = 0.003 ) and the mental component summary ( p = 0.036 ) . Changes were also found for pressure pain sensitivity at the site of maximal pain ( p = 0.022 ) . Five adverse events were reported . Conclusions : Cupping massage appears to be effective in reducing pain and increasing function and quality of life in patients with chronic non-specific neck pain . More rigorous studies are needed to confirm and extend these results Chronic neck pain is a major public health problem with very few evidence -based complementary treatment options . This study aim ed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage , compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain . Patients were r and omly assigned to self-directed cupping massage or progressive muscle relaxation . They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks . Primary outcome measure was the current neck pain intensity ( 0–100 mm visual analog scale ; VAS ) after 12 weeks . Secondary outcome measures included pain on motion , affective pain perception , functional disability , psychological distress , wellbeing , health-related quality of life , pressure pain thresholds and adverse events . Sixty one patients ( 54.1±12.7 years ; 73.8%female ) were r and omized to cupping massage ( n = 30 ) or progressive muscle relaxation ( n = 31 ) . After treatment , both groups showed significantly less pain compared to baseline however without significant group differences . Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds . In conclusion , cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain . Both therapies can be easily used at home and can reduce pain to a minimal clinical ly relevant extent . Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger sample s and longer follow-up periods are needed to confirm these results . Trial Registration Clinical Trials.gov Introduction Cupping is used in various traditional medicine forms to relieve pain in musculoskeletal diseases . The aim of this study was to investigate the effectiveness of cupping in relieving the symptoms of knee osteoarthritis ( OA ) . Methods In a two-group , r and omized controlled exploratory pilot study patients with a clinical ly and radiological confirmed knee OA ( Kellgren-Lawrence Grading Scale : 2 - 4 ) and a pain intensity > 40 mm on a 100 mm visual analogue scale ( VAS ) were included . 40 Patients were r and omized to either 8 sessions of pulsatile dry cupping within 4 weeks or no intervention ( control ) . Paracetamol was allowed on dem and for both groups . Outcomes were the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) score , the pain intensity on a VAS ( 0 mm = no pain to 100 mm = maximum intensity ) and Quality of Life ( SF-36 ) 4 and 12 weeks after r and omization . Use of Paracetamol was documented within the 4-week treatment period . Analyses were performed by analysis of covariance adjusting for the baseline value for each outcome . Results 21 patients were allocated to the cupping group ( 5 male ; mean age 68 ± SD 7.2 ) and 19 to the control group ( 8 male ; 69 ± 6.8 ) . After 4 weeks the WOMAC global score improved significantly more in the cupping group with a mean of 27.7 ( 95 % confidence interval 22.1 ; 33.3 ) compared to 42.2 ( 36.3 ; 48.1 ) in the control group ( p = 0.001 ) . After 12 weeks the WOMAC global score were still significantly different in favor for cupping ( 31.0 ( 24.9 ; 37.2 ) vs. 40.8 ( 34.4 ; 47.3 ) p = 0.032 ) , however the WOMAC subscores for pain and stiffness were not significant anymore . Significantly better outcomes in the cupping group were also observed for pain intensity on VAS and for the SF-36 Physical Component Scale compared to the control group after 4 and 12 weeks . No significant difference was observed for the SF-36 Mental Component Scale and the total number of consumed Paracetamol tablets between both groups ( mean 9.1 , SD ± 20.0 vs. 11.5 ± 15.9 ) . Conclusion In this exploratory study dry cupping with a pulsatile cupping device relieved symptoms of knee OA compared to no intervention . Further studies comparing cupping with active treatments are needed . Trial registration Clinical trials.gov Identifier : Background We aim ed to investigate the effectiveness of two different forms of dry pulsatile cupping in patients with chronic low back pain ( cLBP ) compared to medication on dem and only in a three-armed r and omized trial . Methods 110 cLBP patients were r and omized to regular pulsatile cupping with 8 treatments plus paracetamol on dem and ( n = 37 ) , minimal cupping with 8 treatments plus paracetamol on dem and ( n = 36 ) or the control group with paracetamol on dem and only ( n = 37 ) . Primary outcome was the pain intensity on a visual analogue scale ( VAS , 0–100 mm ) after 4 weeks , secondary outcome parameter included VAS pain intensity after 12 weeks , back function as measured with the ‘ Funktionsfragebogen Hannover Rücken ’ ( FFbH-R ) and health related quality of life question naire Short form 36 ( SF-36 ) after 4 and 12 weeks . Results The mean baseline-adjusted VAS after 4 weeks was 34.9 mm ( 95 % CI : 28.7 ; 41.2 ) for pulsatile cupping , 40.4 ( 34.2 ; 46.7 ) for minimal cupping and 56.1 ( 49.8 ; 62.4 ) for control group , result ing in statistically significant differences between pulsatile cupping vs. control ( 21.2 ( 12.2 ; 30.1 ) ; p < 0.001 ) and minimal cupping vs. control ( 15.7 ( 6.9 ; 24.4 ) ; p = 0.001 ) . After 12 weeks , mean adjusted VAS difference between pulsatile cupping vs. control was 15.1 ( ( 3.1 ; 27.1 ) ; p = 0.014 ) , and between minimal cupping vs. control 11.5 ( ( − 0.44 ; 23.4 ) ; p = 0.059 ) . Differences of VAS between pulsatile cupping and minimal cupping showed no significant differences after 4 or 12 weeks . Pulsatile cupping was also better ( − 5.8 ( − 11.5;-0.1 ) ; p = 0.045 ) compared to control for back function after 4 weeks , but not after 12 weeks ( − 5.4 ( − 11.7;0.8 ) ; p = 0.088 ) , pulsatile cupping also showed better improvements on SF-36 physical component scale compared to control at 4 and 12 weeks ( − 5.6 ( − 9.3;-2.0 ) ; p = 0.003 ; − 6.1 ( − 9.9;-2.4 ) ; p = 0.002 ) . For back function and quality of life minimal cupping group was not statistically different to control after 4 and 12 weeks . Paracetamol intake did not differ between the groups ( cupping vs. control ( 7.3 ( − 0.4;15.0 ) ; p = 0.063 ) ; minimal cupping vs. control ( 6.3 ( − 2.0;14.5 ) ; p = 0.133 ) . Conclusions Both forms of cupping were effective in cLBP without showing significant differences in direct comparison after four weeks , only pulsatile cupping showed effects compared to control after 12 weeks . Trial registration The study was registered at Clinical Trials.gov ( identifier : NCT02090686 ) Objectives Chronic nonspecific lower back pain ( LBP ) is a common disease . Insufficient data is currently available to conclusively confirm the analgesic effects of laser acupuncture on LBP . This study evaluated the effectiveness of laser acupuncture plus Chinese cupping in LBP treatment . Methods Patients with chronic nonspecific LBP were enrolled for a r and omized controlled trial and assigned to the laser acupuncture group ( laser acupuncture plus Chinese cupping ) and control group ( sham laser plus Chinese cupping ) . Laser acupuncture ( 808 nm ; 40 mW ; 20 Hz ; 15 J/cm2 ) and Chinese cupping were applied on the Weizhong ( BL40 ) and Ashi acupoints for 5 consecutive days . Plasma cortisol levels were assessed before and after the 5-day treatment session . The visual analog scale ( VAS ) scores were recorded at baseline and throughout the 5-day treatment session . Results After the treatment session , the plasma cortisol levels and VAS scores decreased significantly in both groups . In the laser acupuncture group , the VAS scores decreased significantly on days 4 and 5 , and an enhanced reduction in VAS scores was observed . Conclusion Laser acupuncture plus Chinese cupping at the Weizhong ( BL40 ) and Ashi acupoints effectively reduced pain and inflammation in chronic nonspecific LBP . This therapy could be a suitable option for LBP treatment in clinical setting Background Persistent non-specific low back pain ( PNSLBP ) is one of the most frequently experienced types of back pain around the world . Wet-cupping is a common intervention for various pain conditions , especially in Korea . In this context , we conducted a pilot study to determine the effectiveness and safety of wet-cupping treatment for PNSLBP . Methods We recruited 32 participants ( 21 in the wet-cupping group and 11 in the waiting-list group ) who had been having PNSLBP for at least 3 months . The participants were recruited at the clinical research centre of the Korea Institute of Oriental Medicine , Korea . Eligible participants were r and omly allocated to wet-cupping and waiting-list groups . Following the practice of traditional Korean medicine , the treatment group was provided with wet-cupping treatment at two acupuncture points among the BL23 , BL24 and BL25 6 times within 2 weeks . Usual care , including providing brochures for exercise , general advice for PNSLBP and acetaminophen , was allowed in both groups . Separate assessors participated in the outcome assessment . We used the 0 to100 numerical rating scale ( NRS ) for pain , the McGill Pain Question naire for pain intensity ( PPI ) and the Oswestry Disability Question naire ( ODQ ) , and we assessed acetaminophen use and safety issues . Results The results showed that the NRS score for pain decreased ( -16.0 [ 95 % CI : -24.4 to -7.7 ] in the wet-cupping group and -9.1 [ -18.1 to -0.1 ] in the waiting-list group ) , but there was no statistical difference between the groups ( p = 0.52 ) . However , the PPI scores showed significant differences between the two groups ( -1.2 [ -1.6 to -0.8 ] for the wet-cupping group and -0.2 [ -0.8 to 0.4 ] for the waiting-list group , p < 0.01 ) . In addition , less acetaminophen was used in the wet-cupping group during 4 weeks ( p = 0.09 ) . The ODQ score did not show significant differences between the two groups ( -5.60 [ -8.90 to -2.30 ] in the wet-cupping group and -1.8 [ -5.8 to 2.2 ] in the waiting-list group , p = 0.14 ) . There was no report of adverse events due to wet-cupping . Conclusion This pilot study may provide preliminary data on the effectiveness and safety of wet-cupping treatments for PNSLBP . Future full-scale r and omised controlled trials will be needed to provide firm evidence of the effectiveness of this intervention . Trial Registration Clinical Trials.gov : ( Identifier : NCT00925951 ) Date of trial registration : June 19th , 2009The date when the first patient was r and omised : July 15th , 2009The date when the study was completed : November 27th , Background In this preliminary trial we investigated the effects of dry cupping , an ancient method for treating pain syndromes , on patients with chronic non-specific neck pain . Sensory mechanical thresholds and the participants ' self-reported outcome measures of pain and quality of life were evaluated . Methods Fifty patients ( 50.5 ± 11.9 years ) were r and omised to a treatment group ( TG ) or a waiting-list control group ( WL ) . Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks ; the control group did not . Self-reported outcome measures before and after the cupping series included the following : Pain at rest ( PR ) and maximal pain related to movement ( PM ) on a 100-mm visual analogue scale ( VAS ) , pain diary ( PD ) data on a 0 - 10 numeric rating scale ( NRS ) , Neck Disability Index ( NDI ) , and health-related quality of life ( SF-36 ) . In addition , the mechanical-detection thresholds ( MDT ) , vibration-detection thresholds ( VDT ) , and pressure-pain thresholds ( PPT ) were determined at pain-related and control areas . Results Patients of the TG had significantly less pain after cupping therapy than patients of the WL group ( PR : Δ-22.5 mm , p = 0.00002 ; PM : Δ-17.8 mm , p = 0.01 ) . Pain diaries ( PD ) revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session ( Δ-1.1 , p = 0.001 ) . There were also significant differences in the SF-36 subscales for bodily pain ( Δ13.8 , p = 0.006 ) and vitality ( Δ10.2 , p = 0.006 ) . Group differences in PPT were significant at pain-related and control areas ( all p < 0.05 ) , but were not significant for MDT or VDT . Conclusions A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain . Not only subjective measures improved , but also mechanical pain sensitivity differed significantly between the two groups , suggesting that cupping has an influence on functional pain processing . Trial registration The trial was registered at clinical trials.gov ( NCT01289964 ) The research aim ed to investigate the effectiveness of cupping therapy ( CT ) in changes on skin surface temperature ( SST ) for relieving chronic neck and shoulder pain ( NSP ) among community residents . A single-blind experimental design constituted of sixty subjects with self-perceived NSP . The subjects were r and omly allocated to two groups . The cupping group received CT at SI 15 , GB 21 , and LI 15 acupuncture points , and the control group received no intervention . Pain was assessed using the SST , visual analog scale ( VAS ) , and blood pressure ( BP ) . The main results were SST of GB 21 acupuncture point raised from 30.6 ° C to 32.7 ° C and from 30.7 ° C to 30.6 ° C in the control group . Neck pain intensity ( NPI ) severity scores were reduced from 9.7 to 3.6 in the cupping group and from 9.7 to 9.5 in the control group . The SST and NPI differences between the groups were statistically significant ( P < 0.001 ) . One treatment of CT is shown to increase SST . In conjunction with the physiological effect the subjective experience of NSP is reduced in intensity . Further studies are required to improve the underst and ing and potential long-term effects of CT UNLABELLED Chronic pain causes functional incapacity and compromises an individual 's affective , social , and economic life . OBJECTIVE To study the cognitive behavioral therapy ( CBT ) effectiveness in a group of patients with chronic pain . METHODS A r and omized clinical trial with two parallel groups comprising 93 patients with chronic pain was carried out . Forty-eight patients were su bmi tted to CBT and 45 continued the st and ard treatment . The visual analogue , hospital anxiety and depression , and quality of life SF-36 scales were applied . Patients were evaluated before and after ten weeks of treatment . RESULTS When the Control Group and CBT were compared , the latter presented reduction of depressive symptoms ( p=0.031 ) and improvement in the domains ' physical limitations ' ( p=0.012 ) , ' general state of health ' ( p=0.045 ) , and ' limitations by emotional aspects ' ( p=0.025 ) . CONCLUSIONS The CBT was effective and it has caused an improvement in more domains of quality of life when compared to the Control Group , after ten weeks of treatment Background : Pneumatic pulsation therapy may combine the effects of cupping therapy and massage . This study investigated the effect of pneumatic pulsation therapy on chronic neck pain compared to st and ard medical care . Methods : 50 patients ( 79.15 % female ; 46.17 ± 12.21 years ) with chronic nonspecific neck pain were r and omized to treatment group ( TG ; n = 25 ) or control group ( CG ; n = 25 ) . The TG received 5 pneumatic pulsation treatments over a period of 2 weeks utilizing a mechanical device . Treatment was applied as a combination of moving and stationary pulsating cupping . Main outcome measure was pain intensity in pain diaries ( numerical rating scale ) . Secondary outcome measures included functional disability ( NDI ) , quality of life ( SF-36 ) , and pain at motion . Sensory thresholds , including pressure pain threshold , were measured at pain-related sites . Results : After the intervention , significant group differences occurred regarding pain intensity ( baseline : 4.12 ± 1.45 in TG and 4.20 ± 1.57 in CG ; post-intervention : 2.72 ± 1.62 in TG and 4.44 ± 1.96 in CG ; analysis of covariance : p = 0.001 ) , NDI ( baseline : 25.92 ± 8.23 and 29.83 ; post-intervention : 20.44 ± 10.17 and 28.83 ; p = 0.025 ) , and physical quality of life ( baseline : 43.85 ± 7.65 and 41.66 ± 7.09 ; post-intervention : 47.60 ± 7.93 and 40.49 ± 8.03 ; p = 0.002 ) . Further significant group differences were found for pain at motion ( p = 0.004 ) and pressure pain threshold ( p = 0.002 ) . No serious adverse events were reported . Conclusion : Pneumatic pulsation therapy appears to be a safe and effective method to relieve pain and to improve function and quality of life in patients with chronic neck pain A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis BACKGROUND Cupping , a classic Chinese medicine treatment , is a technique that applies suction cups over soft tissue . Cupping is gaining popularity in physical medicine because of the simplicity in application , minimal adverse effects , and reduction in pain and muscle tenderness . These factors also make it a cost-effective intervention . For this study , cupping was used to treat low back pain ( LBP ) . OBJECTIVE To evaluate the effectiveness of Chinese cupping in acutely reducing pain , decreasing tenderness to palpation , and improving range of motion for patients with subacute or chronic LBP . PATIENTS / SETTING Twenty-one patients who reported back pain for at least 8 weeks volunteered at a multidisciplinary holistic outpatient clinic . INTERVENTION After completion of a medical screening question naire and collection of baseline data , 4 glass cups were applied and pressurized over the lower erector spinae muscles . OUTCOME MEASUREMENTS Baseline data included demographic characteristics and the Oswestry Disability Question naire score . Pre- and postintervention data included perceived pain on a visual analog scale ( VAS ) , lumbar spine range of motion , straight-leg raise test ( SLR ) , and pain-pressure threshold ( PPT ) assessed with a digital force gauge . The data were analyzed by using a Wilcoxon signed-rank test and Spearman rho correlations . RESULTS Of the 17 patients who completed the study , there were significant post-treatment improvements in VAS scores ( p=0.0001 ) , SLR motion on the left ( p=0.043 ) , and lumbar flexion range of motion ( p=0.016 ) and improvements in PPT at all 4 investigated points ( p<0.007 ) . Significant relationships were identified between the improvement in low back flexion with the improvement in PPT at bilateral lumbar paraspinal muscles at the L4 levels and at the left L2 level . CONCLUSIONS Chinese cupping may be a low-risk , therapeutic treatment for the prompt reduction of symptoms associated with subacute and chronic low back pain . Cupping may allow patients to progress to functional movement training in a timely manner by promptly reducing pain and muscle tenderness and improving range of motion OBJECTIVE To observe the clinical effect of cupping combined with acupuncture stimulation of trigger points on lumbar myofascial pain syndrome ( MPS ) . METHODS Sixty MPS patients were r and omly divided into acupuncture + TDP group ( n = 30 ) , and cupping + acupuncture group ( n = 30 ) . Patients in the acupuncture + TDP group were treated by acupuncture stimulation of trigger points and local TDP irradiation , and patients of the cupping + acupuncture group treated by intensive cupping applied to the myofascial b and and acupuncture stimulation of the locus according to the position of muscular tension b and . The therapeutic effects were assessed according to the score of the McGill pain question naire composing of pain rating index ( PRI ) , visual analogue scale ( VAS ) and present pain intensity ( PPI ) before , immediately and 1 month after the treatment . RESULTS After the treatment , the total effective rates of the acupuncture+ TDP and cupping + acupuncture groups were 83.3 % ( 25/30 ) and 96.6 % ( 29/30 ) , respectively , without significant difference between the two groups ( P > 0.05 ) . One month 's follow-up showed that the total effective rates of the acupuncture + TDP and cupping + acupuncture groups were 40.0 % and 90.0 % respectively , and the latter group was significantly better than the acupuncture + TDP group in the therapeutic effect ( P < 0.05 ) . The scores of PRI , VAS , PPI after the treatment were markedly decreased in both groups ( P < 0.05 ) . One month later , the scores of PRI , VAS and PPI in the cupping + acupuncture group were obviously lower than those of the acupuncture group ( P < 0.05 ) . CONCLUSION Both acupuncture stimulation of trigger points plus TDP and cupping plus acupuncture can effectively relieve pain in MPS patients , while the therapeutic effect of cupping plus acupuncture treatment lasts longer analgesic effect UNLABELLED Palpation is widely used to assess muscular sensitivity in clinical setting s but still remains a subjective evaluation . This cross-sectional study assessed a newly developed cross-friction algometry making palpation measurable . The objective was to investigate the reliability of pressure pain thresholds obtained using Cross-Friction Algometry ( CFA-PPTs ) measured at the level of Erector spinae and Gluteus maximus central muscle parts , and to compare the CFA-PPTs between patients with chronic nonspecific low back pain ( nCLBP ) and matching healthy subjects . PARTICIPANTS Patients presenting nCLBP to GP 's and send into a Pain Center and healthy subjects recruited via university ad valvas & flyers distribution . OUTCOME MEASURES 30 patients with nCLBP were measured for cross-friction algometry . Other evaluations consisted of the Visual Analogue Scale ( VAS ) and the Oswestry Disability Index ( ODI ) . RESULTS The inter- and intra-reliability were tested and found to be sufficient . The mean CFA-PPT values of the Erector spinae at levels T8 , T10 , L1 & L3 and the Gluteus maximus of the nCLBP group were significantly lower ( p ≤ 0.001 ) when compared to the CFA-PPT values of the healthy group . The greatest difference ( -58 % ) was found at L1 Erector spinae level and at the superior part of the Gluteus maximus measuring point ( -59 % ) . Within the group of patients with nCLBP it was surprising to notice that there was no significant correlation between all the reference points measured using CFA-PPTs and the outcomes of the VAS and ODI scores . CONCLUSIONS With the aid of CFA , the importance of local muscular disorder in the lumbar part of the Erector spinae and Gluteus maximus in patients with nCLBP is obviously demonstrated , but also reveals the very large inter-individual differences in muscular fibrosis sensitivity and /or pain behavior in daily life . This possibly re-opens the debate on which influences can be put forward as the most important : the central or the peripheral sensitization system |
2,177 | 31,657,610 | The most effective intervention among the studies was the replacement of caloric beverages with water .
In conclusion , despite 5.15 % of weight loss , the low to moderate quality of evidence and the short term of follow-up are limitations to support evidence -based recommendations of water consumption for weight loss | Water intake has been proposed for weight loss ; however , the evidence of its efficacy is limited .
The aim of this study was to systematic ally review the r and omized clinical trials that assessed the effect of water consumption on weight with a follow up ≥ 12 weeks . | Objective To evaluate the effects of water versus beverages sweetened with non‐nutritive sweeteners ( NNS ) on body weight in subjects enrolled in a year‐long behavioral weight loss treatment program . Methods The study used a r and omized equivalence design with NNS or water beverages as the main factor in a trial among 303 weight‐stable people with overweight and obesity . All participants participated in a weight loss program plus assignment to consume 24 ounces ( 710 ml ) of water or NNS beverages daily for 1 year . Results NNS and water treatments were non‐equivalent , with NNS treatment showing greater weight loss at the end of 1 year . At 1 year subjects receiving water had maintained a 2.45 ± 5.59 kg weight loss while those receiving NNS beverages maintained a loss of 6.21 ± 7.65 kg ( P < 0.001 for difference ) . Conclusions Water and NNS beverages were not equivalent for weight loss and maintenance during a 1‐year behavioral treatment program . NNS beverages were superior for weight loss and weight maintenance in a population consisting of regular users of NNS beverages who either maintained or discontinued consumption of these beverages and consumed water during a structured weight loss program . These results suggest that NNS beverages can be an effective tool for weight loss and maintenance within the context of a weight management program BACKGROUND The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks . Our aim was to examine this relation . METHODS We enrolled 548 ethnically diverse schoolchildren ( age 11.7 years , SD 0.8 ) from public schools in four Massachusetts communities , and studied them prospect ively for 19 months from October , 1995 , to May , 1997 . We examined the association between baseline and change in consumption of sugar-sweetened drinks ( the independent variables ) , and difference in measures of obesity , with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools . FINDINGS For each additional serving of sugar-sweetened drink consumed , both body mass index ( BMI ) ( mean 0.24 kg/m2 ; 95 % CI 0.10 - 0.39 ; p=0.03 ) and frequency of obesity ( odds ratio 1.60 ; 95 % CI 1.14 - 2.24 ; p=0.02 ) increased after adjustment for anthropometric , demographic , dietary , and lifestyle variables . Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI ( mean 0.18 kg/m2 for each daily serving ; 95 % CI 0.09 - 0.27 ; p=0.02 ) . INTERPRETATION Consumption of sugar-sweetened drinks is associated with obesity in children Dietary compensation for energy provided as ethanol is reportedly limited . Whether this is a function of the ethanol or other aspect of the medium in which it is ingested is not known . Eight male and eight female adults ingested 1.08 liters of beer ( 5.0 % ethanol w/v , 1891kJ ) , light beer ( 2.9 % ethanol w/v , 1197kJ ) , no-alcohol beer ( 0.1 % ethanol w/v , 816kJ ) , cola ( 1749kJ ) or carbonated water ( 0kJ ) every 3 - 4 days with a midday meal . Diet records were kept the preceding day and day of beverage ingestion . Energy intake was significantly higher each day an energy-bearing beverage was consumed relative to its preceding day . A literature review revealed dietary compensation for modifications of energy intake via fluids is less precise than when solid foods are manipulated . These findings demonstrate dietary adjustment for energy derived from ethanol is imprecise , but also indicate energy from carbohydrate elicits little dietary response when ingested in a beverage Whereas soft drinks are described as primarily thirst-quenching liquids , juices and milk are said to be liquid foods , with a greater satiating power . This study was conducted to compare the effects of orange juice , low-fat milk ( 1 % ) , regular cola , and sparkling water on hunger , thirst , satiety , and energy intakes at the next meal . Thirty-two volunteers ( 14 men and 18 women ) , ages 18 - 35 years , consumed a breakfast preload composed of 590 ml ( 20 oz ) of an energy-containing beverage ( 1036 kJ ) or water ( 0 kJ ) and a slice of toast ( 418 kJ ) on four different occasions . Participants rated hunger , thirst , fullness , and desire to eat at baseline and at 20-min intervals for 2 h following preload ingestion . A tray lunch was presented at 2 h , 15 min and food consumption was measured . Compared to sparkling water , the three energy-containing beverages were associated with higher fullness and reduced hunger rating and desire to eat . However , energy intakes at lunch ( 4511+/-151 kJ for men and 3183+/-203 kJ for women ) were the same across all four beverage conditions and no compensation for breakfast energy was observed . The three beverages of equal energy value were significantly different from sparkling water , but not from each other , in their effects on hunger and satiety ratings . All four beverages satisfied thirst equally well . Whether energy-containing cola , juice , and low-fat milk facilitate a positive energy balance remains a topic for further study Objective The present study evaluated weight loss and compliance outcomes for overweight adolescents assigned to one of two dietary interventions differing in the type of snacks allowed . Methods The study was a 12-week , controlled clinical trial , among otherwise healthy but overweight ( body mass index ≥95th percentile ) 11-year-old to 15-year-old girls who were r and omly assigned to either a 1,500 kcal/day free-snack program or a 1,500 kcal/day restricted-snack program . All subjects were counseled to consume three servings of dairy products per day , and were provided with a 500 mg calcium supplement as well . Subjects in the free-snack group could choose any 150-calorie item as one of their two daily snacks , including regular soda if desired ; however , subjects in the restricted-snack group were limited to diet soda . Results Thirty-two adolescent girls completed the 12-week intervention . Both diets were equally effective in achieving a modest amount of weight loss , and were equally acceptable to the subjects . Significant decreases in weight , body mass index , anthropometric measures , total cholesterol and triglycerides were observed . Conclusions A 1,500 kcal/day diet allowing for a free snack of 150 calories was equally as effective as a more restricted snack policy in achieving a modest amount of weight loss among overweight 11-year-old to 15-year-old girls . In addition , results suggest that some soda may be included in a teen weight control diet , as long as caloric intake is maintained at recommended levels , and care is taken to achieve adequate intake of essential nutrients . Calcium intake among subjects was low at baseline , and , although it increased during the study ( due to supplementation ) , further efforts to increase consumption of naturally calcium-rich and calcium-fortified foods and beverages are needed BACKGROUND A population of over 12,000 mature subjects participated in a longitudinal study ( 8 years ) of nutrition and health ( the Su . Vi . Max Study ) . In this context , a specific cross-sectional study was carried out in a r and omly selected sub population . AIM To identify anthropometric , nutritional and biochemical correlates of spontaneous use of ' light ' foods and drinks in a free-living population . DESIGN Men ( n = 2299 ) and women ( n = 1979 ) , 45 - 60 years , reported their food intakes over six non-consecutive days . Consumers of low-fat and low-sugar foods and drinks , and artificial sweeteners , were compared with non-consumers . RESULTS Users of low-sugar products were heavier than non-users ; female consumers of low-fat products , but not males , had higher body weight and BMI than non-consumers . Users of low-sugar products had higher triacylglycerols and glycaemia than non-users while biochemical parameters were not different in users and non-users of low-fat products . Use of low-sugar products led to increased diet density of a few micronutrients , including cholesterol . Low-fat product selection was associated with increased intake of most micronutrients , both in absolute value and in density . CONCLUSIONS In mature adults , selection of fat-reduced products was associated with improved quality of the diet , while anthropometric and biological parameters appeared less favourable in consumers of low-sugar products vs. non-consumers . The longitudinal follow-up of the cohort in future years will help determine cause- and -effect relationships among these parameters OBJECTIVE To examine the secular trends in the association between obesity and hypertension among American adults between 1999 and 2014 . METHODS Data from the 1999 - 2014 National Health and Nutrition Examination Survey ( eight survey cycles ) were used . Obesity was determined from measured body mass index , with hypertension assessed from measured blood pressure and self-reported medication use . Meta-regression was used to examine the linear , quadratic , and cubic trends of the relationship between the observed odds ratio effect sizes ( obesity and hypertension ) and the NHANES cycles ( year ) using a r and om-effects model . RESULTS Across the years of 1999 to 2014 , there was a significant , positive linear trend ( p = .006 ) in the association between overweight/obesity and hypertension . CONCLUSION Our findings suggest that the association between overweight/obesity and hypertension is becoming stronger over time . Continued surveillance of temporal changes associated with obesity and hypertension is necessary to monitor how such changes may underlie changes in the risk for chronic disease . SIGNIFICANCE OF THE STUDY This novel study evaluates whether the magnitude of association between obesity and hypertension has changed over the last 15-years Importance Health care professionals commonly recommend increased water consumption , typically to 8 cups per day , as part of a weight-reducing diet . However , this recommendation is based on limited evidence and virtually no experimental data from the pediatric population . Objective To compare 2 st and ardized weight-loss diets among adolescents with overweight or obesity , either with or without additional advice and behavioral support to increase habitual water intake to 8 cups per day . Design , Setting , and Participants A r and omized clinical , parallel-group trial was conducted between February 2 , 2011 , and June 26 , 2014 , at Boston Children ’s Hospital , Boston , Massachusetts , among 38 adolescents with overweight or obesity who reported drinking 4 cups or less of water per day . Interventions All participants in both groups received similar weight-reducing interventions , differentiated by advice about water intake ( the water group received advice to increase water intake to 8 cups per day ; the control group did not receive such advice ) but controlled for other dietary recommendations and treatment intensity . The interventions included dietary counseling , daily text messages , and a cookbook with health guides . To support adherence to 8 cups of water per day , the water group received well-defined messages about water through counseling and daily text messages , a water bottle , and a water pitcher with filters . Main Outcomes and Measures The primary outcome was 6-month change in body mass index z score . Data analyses followed the intention-to-treat principle . Results All 38 participants ( 27 girls and 11 boys ; mean [ SD ] age , 14.9 [ 1.7 ] years ) completed the study . Both groups reported drinking approximately 2 cups of water per day at baseline . Self-reported change in water intake at 6 months was greater in the water group ( difference from baseline , 2.8 cups per day [ 95 % CI , 1.8 to 3.8 ] ; P < .001 ) compared with that in the control group ( difference from baseline , 1.2 cups per day [ 95 % CI , 0.2 to 2.2 ] ; P = .02 ) ( difference between groups , 1.6 cups per day [ 95 % CI , 0.2 to 3.0 cups per day ] ; P = .03 ) . The 6-month change in body mass index z score did not differ between the water group ( difference from baseline , –0.1 [ 95 % CI , –0.2 to –0.0 ] ; P = .005 ) and the control group ( difference from baseline , –0.1 [ 95 % CI , –0.2 to –0.0 ] ; P = .008 ) ( difference between groups , –0.0 [ 95 % CI , −0.1 to 0.1 ] ; P = .88 ) . Conclusions and Relevance Advice and behavioral supports to consume 8 cups of water per day in the context of a weight-reducing diet did not affect body weight among adolescents with overweight or obesity . Despite intensive behavior supports , few adolescents achieved the target of 8 cups of water per day . Environmental interventions to reduce barriers to water consumption at school may be necessary in future research of the feasibility and effectiveness to achieve the target of an intake of 8 cups of water per day in adolescents . Trial Registration clinical trials.gov Identifier : OBJECTIVE To investigate the efficacy of water preloading before meals as a weight loss strategy for adults with obesity . METHODS A two-group r and omized controlled trial was conducted in Birmingham , Engl and . Eighty-four adults with obesity were recruited from general practice s. All participants were given a face-to-face weight management consultation at baseline ( 30 min ) and a follow-up telephone consultation at 2 weeks ( 10 min ) . At baseline , participants were r and omized to either drinking 500 ml of water 30 min before their main meals or an attention control group where participants were asked to imagine their stomach was full before meals . The primary outcome was weight change at 12-week follow-up . Several measures of adherence were also used , including 24 h total urine collection s. RESULTS 41 participants were r and omized to the intervention group and 43 to the comparator group . The water preloading group lost -1.3 kg ( 95 % CI -2.4 to -0.1 , P = 0.028 ) more than comparators at follow up . Adjusting for ethnicity , deprivation , age , and gender result ed in the intervention group losing -1.2 kg ( 95 % CI -2.4 to 0.07 , P = 0.063 ) more than the comparator . CONCLUSIONS There is preliminary evidence that water preloading before main meals leads to a moderate weight loss at follow up . IS RCT N33238158 |
2,178 | 19,261,953 | Audit and feedback , together with educational outreach visits , were the focus of the majority of recent , high- quality research into prescribing interventions .
These interventions were also the most effective in improving prescribing practice .
There is insufficient recent research into manual reminders to confidently up date earlier review s and there remains insufficient evidence to draw conclusions regarding the effectiveness of local consensus processes or multidisciplinary teams .
Conclusions : Educational outreach as well as audit and feedback continue to dominate research into prescribing interventions .
These 2 prescribing interventions also most consistently show positive results . | Objective : To up date 2 comprehensive review s of systematic review s on prescribing interventions and identify the latest evidence about the effectiveness of the interventions . | Background : The effect of regular and expected printed educational material s on physician prescribing behaviour has not been studied . We sought to measure the impact of a series of evidence -based drug therapy letters mailed to physicians in British Columbia on prescribing to newly treated patients . Methods : A paired , cluster r and omized community design was used . The study population included 499 physicians from 24 local health areas in British Columbia . Local health areas were paired by number of physicians , and 1 of each pair was r and omly selected and its physicians assigned to an intervention group or a control group . The intervention was 12 issues of an evidence -based series called Therapeutics Letter . Physicians in the control group ( n = 241 ) received the letters 3–8 months after physicians in the intervention group ( n = 258 ) . The impact on prescribing to newly treated patients ( defined as patients who had not previously made a cl aim for any medication from the class of drugs profiled in the letter ) was analyzed using the drug cl aims data base of BC Pharmacare , a publicly funded drug benefits program that covered all seniors and people receiving social assistance . Results : The probability of prescribing a drug recommended in the Therapeutics Letter rather than another drug in the same class increased by 30 % in the 3 months after the mailing of the letter relative to the preceding 3 months , adjusted for any before – after changes in the control group ( relative risk 1.30 ; 95 % confidence interval 1.13–1.52 ) . No letter achieved statistical significance on its own . However , 11 of the 12 letters produced prescribing changes in the predicted direction such that the overall result was significant when their effect was combined . Interpretation : The combined effect of an ongoing series of printed letters distributed from a credible and trusted source can have a clinical ly significant effect on prescribing to newly treated patients Background R and omised controlled trials of implementation strategies tell us whether ( or not ) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change . Theory-based process evaluations collect data on theoretical constructs alongside r and omised trials to explore possible causal mechanisms and effect modifiers . This is similar to measuring intermediate endpoints in clinical trials to further underst and the biological basis of any observed effects ( for example , measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths).This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message ( OPEM ) trial . We hypothesize that the OPEM interventions are most likely to operate through changes in physicians ' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control . We will test this hypothesis using a well-vali date d social cognition model , the theory of planned behaviour ( TPB ) that incorporates these constructs . Methods / design We will develop theory-based surveys using st and ard methods based upon the TPB for the second and third replications , and survey a sub sample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed , the evidence based newsletter used for the interventions . In the third replication , our study will converge with the " TRY-ME " protocol ( a second study conducted alongside the OPEM trial ) , in which the content of educational messages was constructed using both st and ard methods and methods informed by psychological theory . We will modify Dillman 's total design method to maximise response rates . Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable ( intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension ) . We will then compare groups using methods appropriate for comparing independent sample s to determine whether there have been changes in the predicted constructs ( attitudes , subjective norms , or intentions ) across the study groups as hypothesised , and will assess the convergence between the process evaluation results and the main trial results .Trial registration numberCurrent controlled trial IS RCT OBJECTIVES To assess the feasibility of a multifaceted strategy to translate evidence -based guidelines for treating nursing home-acquired pneumonia ( NHAP ) into practice using a small intervention trial . DESIGN Pre-posttest with untreated control group . SETTING Two Colorado State Veterans Homes ( SVHs ) during two influenza seasons . PARTICIPANTS Eighty-six residents with two or more signs of lower respiratory tract infection . INTERVENTION Multifaceted , including a formative phase to modify the intervention , institutional-level change emphasizing immunization , and availability of appropriate antibiotics ; interactive educational sessions for nurses ; and academic detailing . MEASUREMENTS Subjects ' SVH medical records were review ed for guideline compliance retrospectively for the influenza season before the intervention and prospect ively during the intervention . Bivariate comparisons-of-care processes between the intervention and control facility before and after the intervention were made using the Fischer exact test . RESULTS At the intervention facility , compliance with five of the guidelines improved : influenza vaccination , timely physician response to illness onset , x-ray for patients not being hospitalized , use of appropriate antibiotics , and timely antibiotic initiation for unstable patients . Chest x-ray and appropriate and timely antibiotics were significantly better at the intervention than at the control facility during the intervention year but not during the control year . CONCLUSION Multifaceted , evidence -based , NHAP guideline implementation improved care processes in a SVH . Guideline implementation should be studied in a national sample of nursing homes to determine whether it improves quality of life and functional outcomes of this debilitating illness for long-term care residents OBJECTIVES . To determine whether we could increase adherence to the Centers for Disease Control and Prevention ( CDC ) recommendations with well-accepted approaches to improving quality of care and adherence to the CDC recommendations result ed in improved outcomes for acute otitis media ( AOM ) . METHODS . A cluster r and omization study was conducted in 12 pediatric practice s ( 6 intervention and 6 control sites ) . The main outcome measures were adherence to the CDC recommendations ( modified to include 2 additional antimicrobial agents ) and a subsequent antibiotic prescription for AOM within 30 days after diagnosis . RESULTS . Of 3152 patients referred to research assistants , 2584 ( 82 % ) were eligible . Of those eligible , 1368 ( 99 % ) of 1382 at the intervention sites and 1138 ( 99 % ) of 1146 at the control sites consented to participate . Rates of adherence to the CDC recommendations were not significantly higher at the intervention sites than at the control sites , for initial enrollment episodes ( 78.2 % vs 70.6 % ) or second episodes ( 62.6 % vs 59.9 % ) . After controlling for clustering according to site and covariates , children who were not treated in adherence to the CDC recommendations for both episodes had 1.60 times the odds of a subsequent prescription within 12 days , compared with those treated in adherence at both episodes . CONCLUSIONS . Despite using evidence -based approaches that are known to influence physician behavior , we were unable to increase adherence to the CDC recommendations for treatment of AOM . However , we did establish that prescription of antimicrobial therapy consistent with the CDC recommendations for a second episode of AOM was associated with improved outcomes , measured as the need for subsequent antibiotic prescription . Because of the selection of resistant otopathogens , adherence to the CDC recommendations is likely more important in subsequent episodes of AOM than in the initial episode Objectives : To evaluate the impact of using pain assessment scales on the management of musculoskeletal chronic pain . Methods : Cluster-r and omized controlled multicentre trial in French general practice setting s. Practice s were r and omized by region before patient recruitment . The inclusion concerned patients suffering from musculoskeletal chronic pain . General practitioners assigned to the scale group used two vali date d assessment instruments ; those assigned to the control group cared for their patients according to their usual practice . The primary end-point was the level of relief obtained and the secondary changes in prescription of painkilling modalities . Results : A total of 155 general practitioners included 772 successive patients suffering from musculoskeletal chronic pain . The control group reported a mean level of relief of 50.7 % compared with one of 41.1 % in the scale group ( p<0.0001 ) . In the intervention group , physicians decreased significantly their prescription of level two painkillers . Conclusions . In general practice , the use of pain assessment scales is not associated with greater pain relief . The lesser level of pain relief obtained in the scale group does provide evidence that using pain assessment scales does not enhance the relief of chronic pain in patients in primary care . Guidelines which recommend the systematic use of scales for the assessment and monitoring of chronic pain are not tailored to either the context or the patients encountered in the primary care setting Background A challenge for implementation research ers is to develop principles that could generate testable hypotheses that apply across a range of clinical context s , thus leading to generalisability of findings . Such principles may be provided by systematic ally developed theories . The opportunity has arisen to test some of these theoretical principles in the Ontario Printed Educational Material s ( OPEM ) trial by conducting a sub-trial within the existing trial structure . OPEM is a large factorial cluster-r and omised trial evaluating the effects of short directive and long discursive educational messages embedded into informed , an evidence -based newsletter produced in Canada by the Institute for Clinical Evaluative Sciences ( ICES ) and mailed to all primary care physicians in Ontario . The content of educational messages in the sub-trial will be constructed using both st and ard methods and methods inspired by psychological theory . The aim of this study is to test the effectiveness of the TheoRY-inspired MEssage ( ' TRY-ME ' ) compared with the ' st and ard ' message in changing prescribing behaviour . Methods The OPEM trial participants r and omised to receive the short directive message attached to the outside of informed(an ' outsert ' ) will be sub-r and omised to receive either a st and ard message or a message informed by the theory of planned behaviour ( TPB ) using a two ( long insert or no insert ) by three ( theory-based outsert or st and ard outsert or no outsert ) design . The messages will relate to prescription of thiazide diuretics as first line drug treatment for hypertension ( described in the accompanying protocol , " The Ontario Printed Educational Material s trial " ) . The short messages will be developed independently by two research teams . The primary outcome is prescription of thiazide diuretics , measured by routinely collected data available within ICES . The study is design ed to answer the question , is there any difference in guideline adherence ( i.e. , thiazide prescription rates ) between physicians in the six groups ? A process evaluation survey instrument based on the TPB will be administered pre- and post-intervention ( described in the accompanying protocol , " Looking inside the black box " ) . The second research question concerns processes that may underlie observed differences in prescribing behaviour . We expect that effects of the messages on prescribing behaviour will be mediated through changes in physicians ' cognitions . Trial registration numberCurrent controlled trial IS RCT Background Psychological models can be used to underst and and predict behaviour in a wide range of setting s. However , they have not been consistently applied to health professional behaviours , and the contribution of differing theories is not clear . The aim of this study was to explore the usefulness of a range of psychological theories to predict health professional behaviour relating to management of upper respiratory tract infections ( URTIs ) without antibiotics . Methods Psychological measures were collected by postal question naire survey from a r and om sample of general practitioners ( GPs ) in Scotl and . The outcome measures were clinical behaviour ( using antibiotic prescription rates as a proxy indicator ) , behavioural simulation ( scenario-based decisions to managing URTI with or without antibiotics ) and behavioural intention ( general intention to managing URTI without antibiotics ) . Explanatory variables were the constructs within the following theories : Theory of Planned Behaviour ( TPB ) , Social Cognitive Theory ( SCT ) , Common Sense Self-Regulation Model ( CS-SRM ) , Operant Learning Theory ( OLT ) , Implementation Intention ( II ) , Stage Model ( SM ) , and knowledge ( a non-theoretical construct ) . For each outcome measure , multiple regression analysis was used to examine the predictive value of each theoretical model individually . Following this ' theory level ' analysis , a ' cross theory ' analysis was conducted to investigate the combined predictive value of all significant individual constructs across theories . Results All theories were tested , but only significant results are presented . When predicting behaviour , at the theory level , OLT explained 6 % of the variance and , in a cross theory analysis , OLT ' evidence of habitual behaviour ' also explained 6 % . When predicting behavioural simulation , at the theory level , the proportion of variance explained was : TPB , 31 % ; SCT , 26 % ; II , 6 % ; OLT , 24 % . GPs who reported having already decided to change their management to try to avoid the use of antibiotics made significantly fewer scenario-based decisions to prescribe . In the cross theory analysis , perceived behavioural control ( TPB ) , evidence of habitual behaviour ( OLT ) , CS-SRM cause ( chance/bad luck ) , and intention entered the equation , together explaining 36 % of the variance . When predicting intention , at the theory level , the proportion of variance explained was : TPB , 30 % ; SCT , 29 % ; CS-SRM 27 % ; OLT , 43 % . GPs who reported that they had already decided to change their management to try to avoid the use of antibiotics had a significantly higher intention to manage URTIs without prescribing antibiotics . In the cross theory analysis , OLT evidence of habitual behaviour , TPB attitudes , risk perception , CS-SRM control by doctor , TPB perceived behavioural control and CS-SRM control by treatment entered the equation , together explaining 49 % of the variance in intention . Conclusion The study provides evidence that psychological models can be useful in underst and ing and predicting clinical behaviour . Taking a theory-based approach enables the creation of a replicable methodology for identifying factors that predict clinical behaviour . However , a number of conceptual and method ological challenges remain Abstract Objectives To assess the effectiveness of a multiple intervention aim ed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care . Design R and omised controlled trial . Subjects Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht , Netherl and s. Intervention The intervention consisted of group education meetings , with a consensus procedure on indication for and type of antibiotics and with training in communication skills ; monitoring and feedback on prescribing behaviour ; group education for assistants of general practitioners and pharmacists ; and educational material for patients . The control group did not receive any of these elements . Main outcome measures Antibiotic prescription rates for acute symptoms of the respiratory tract and patients ' satisfaction . Results 89 general practitioners completed the study ( 89 % ) . At baseline , prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group ( 27 % v 29 % , respectively ) . After nine months , the prescription rates in the intervention group fell to 23 % , whereas the control group 's rose to 37 % ( mean difference in change −12 % , 95 % confidence interval −18.9 % to −4.0 % ) . Multilevel analysis confirmed the results of the unadjusted analysis ( intervention effect −10.7 % , −20.3 % to −1.0 % ) . Patients ' satisfaction was high and did not differ in the two groups at baseline or after the intervention . Conclusions A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients . Further research should focus on the sustainability and cost effectiveness of this intervention OBJECTIVES Assessing the efficacy of an educational intervention that aim ed to reduce unnecessary antibiotic prescriptions in primary care by motivating GPs to change their attitudes to communication and by empowering patients . METHODS One hundred and four GPs in North-Rhine/Westphalia-Lippe , Germany were cluster-r and omized into intervention and control . GPs r and omized to receive the intervention were visited by peers . The intervention strategy was focused on the communication within the encounter , not on sharing knowledge about antibiotic prescribing . Leaflets and posters were provided that aim ed at patient empowerment , thus enabling patients to raise the topic of antibiotic prescriptions themselves . RESULTS Eighty-six GPs ( 83 % ) remained in the study at 6 weeks and 61 GPs ( 59 % ) at 12 months . Antibiotic prescription rates within the control group were 54.7 % at baseline and 36.4 % within the intervention group at baseline . Generalized estimating equation models were applied . Baseline imbalances and confounding variables were controlled by adjustment . After the intervention , the ORs for the prescription of an antibiotic dropped to 0.58 [ 95 % CI : ( 0.43;0.78 ) , P < 0.001 ] after 6 weeks and were 0.72 [ 95 % CI : ( 0.54;0.97 ) , P = 0.028 ] after 12 months in the intervention group . In the control group , the ORs rose to 1.52 [ 95 % CI : ( 1.19;1.95 ) , P = 0.001 ] after 6 weeks and were 1.31 [ 95 % CI : ( 1.01;1.71 ) , P = 0.044 ] after 12 months ; these ORs correspond to an approximately 60 % relative reduction in antibiotic prescription rates at 6 weeks and a persistent 40 % relative reduction at 12 months . CONCLUSIONS An interventional strategy that focused on doctor-patient communication and patient empowerment is an effective concept to reduce antibiotic prescriptions in primary care BACKGROUND Hypertension is generally poorly controlled in primary care . One possible intervention for improving control is the harnessing of patient expertise through education and encouragement to challenge their care . AIM To determine whether encouraging patients to manage their hypertension in an ' expert ' manner , by providing them with information in a clear clinical guideline , coupled with an explicit exhortation to become involved in and to challenge their own care if appropriate , would improve their care . DESIGN OF STUDY Single blind r and omised controlled trial of detailed guideline versus st and ard information . SETTING Single urban general practice over 1 year . METHOD Patient-held guideline with written explicit exhortation to challenge care when appropriate . Two hundred and ninety-four of 536 eligible patients on the practice hypertension register were recruited , all of whom were r and omised into one of two groups . Two hundred and thirty-six patients completed the study . RESULTS PRIMARY OUTCOME average systolic blood pressure . SECONDARY OUTCOMES proportion of patients with blood pressure < 150 mmHg systolic and < 90 mmHg diastolic , average cholesterol , proportion of patients prescribed statins and aspirin according to guideline , hospital anxiety and depression score . No clinical ly , or statistically significant differences were found between intervention and control with respect to all parameters or in anxiety and depression levels . Statin and aspirin use improved throughout the course of the study in both groups . Statin use showed a trend ( P = 0.02 ) in favour of control . CONCLUSION In this study there was no clinical ly significant perceived benefit to patients as a result of providing them with a hypertension guideline . Patient guidelines are currently planned for many chronic illnesses . It is important to determine the utility of such interventions before scarce re sources are applied to them BACKGROUND In light of widespread undertreatment for glucocorticoid-induced osteoporosis ( GIOP ) , we design ed a group r and omized controlled trial to increase bone mineral density ( BMD ) testing and osteoporosis medication prescribing among patients receiving long-term glucocorticoid therapy . METHODS Using administrative data bases of a large US health plan , we identified physicians who prescribed long-term glucocorticoid therapy to at least 3 patients . One hundred fifty-three participating physicians were r and omized to receive a 3-module Web-based GIOP intervention or control course . Intervention modules focused on GIOP management and incorporated case-based continuing medical education and personalized audit and feedback of GIOP management compared with that of the top 10 % of study physicians . In the year following the intervention , we compared rates of BMD testing and osteoporosis medication prescribing between intervention and control physicians . RESULTS Following the intervention , intent-to-treat analyses showed that 78 intervention physicians ( 472 patients ) vs 75 control physicians ( 477 patients ) had similar rates of BMD testing ( 19 % vs 21 % , P = .48 ; rate difference , -2 % ; 95 % confidence interval [ CI ] , -8 % to 4 % ) and osteoporosis medication prescribing ( 32 % vs 29 % , P = .34 ; rate difference , 3 % ; 95 % CI , -3 % to 9 % ) . Among 45 physicians completing all modules ( 343 patients ) , intervention physicians had numerically but not significantly higher rates of BMD testing ( 26 % vs 16 % , P = .04 ; rate difference , 10 % ; 95 % CI , 1%-20 % ) and bisphosphonate prescribing ( 24 % vs 17 % , P = .09 ; rate difference , 7 % ; 95 % CI , -1 % to 16 % ) or met a combined end point of BMD testing or osteoporosis medication prescribing ( 54 % vs 44 % , P = .07 ; rate difference , 10 % ; 95 % CI , -1 % to 21 % ) compared with control physicians . CONCLUSIONS In the main analysis , a Web-based intervention incorporating performance audit and feedback and case-based continuing medical education had no significant effect on the quality of osteoporosis care . However , dose-response trends showed that physicians with greater exposure to the intervention had higher rates of GIOP management . New cost-effective modalities are needed to improve the quality of osteoporosis care Objective A major problem with inappropriate use of antibiotics is the emergence of resistance . Thus , cost-effective interventional strategies are required to improve their use . This study aim ed to evaluate the effect of multifaceted interventions on prescribing practice s of antibiotics in health centers of Khartoum State , Sudan . Methods Twenty health centers were r and omly assigned to receive : ( 1 ) no intervention ; ( 2 ) audit and feedback ; ( 3 ) audit and feedback + seminar ; or ( 4 ) audit and feedback + academic detailing . A total of 1,800 patient encounters , 30 from each health center , were r and omly collected . The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice , dose and duration of therapy before the study and at 1 and 3 months post-intervention . Results In comparison to the control group , the prescriber targeted interventions involving audit and feedback , together with academic detailing ( 4 ) , reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . In addition , the mean number of encounters with an inappropriate antibiotic with respect to diagnosis , doses and / or duration of therapy was reduced by 5.3 and 5.9 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . For audit and feedback together with seminars ( 3 ) and for audit and feedback alone ( 2 ) , the corresponding reductions were 5.3 , 7.1 , 4.4 and 5.1 ( p<0.001 ) and 1.4 , 2.8 , 1.8 and 1.9 ( p>0.05 ) , respectively . Conclusion Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State , Sudan , are alarmingly high . Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practice s of antibiotics than audit and feedback alone Background : Although there is a great concern regarding rational use of drugs , the available evidence for the most appropriate strategies to improve prescribing is scarce . Goal : The goal of this study was to evaluate the effectiveness of the combination of feedback of individualized prescribing data and educational recommendations for improving the quality of prescribing in general practice . Method : A quasiexperimental intervention study was conducted in which prescribing rates of 282 family physicians before and after the intervention were compared . Physicians assigned to the individualized feedback group ( n = 195 ) received individual instruction with specific recommendations for improvement according to their baseline prescribing quality levels , whereas physicians in the minimal intervention group ( n = 87 ) only received st and ard nonindividualized prescribing data for the practice group as a whole . Results : A trend toward increasing high pharmacologic intrinsic value in both groups was observed . Overprescription of antibiotics showed a decrease in the individualized feedback group ( P = 0.006 ) and it did not change in the minimal intervention group . A different trend in the values in each group was observed with nonsteroidal antiinflammatory drugs , although it was not statistically significant . Overprescription of antiulcerative agents decreased among physicians in the individualized feedback group ( P = 0.003 ) ; however , there were not statistically significant differences as compared with the minimal intervention group . Changes in indicators of drug selection were more favorable for the group with individualized feedback , although no statistically significant differences were observed . Pharmaceutical expenditure increased significantly in the minimal intervention group as compared with the individualized feedback group , with an approximate difference of $ 7.87 per inhabitant and trimester ( P = 0.003 ) . Conclusion : The intervention showed that improving the quality of prescribing was feasible , particularly in overprescribing , and was associated with considerable savings in pharmaceutical costs BACKGROUND Educational outreach visits , particularly when combined with social marketing , appear to be a promising approach to modifying health professional behaviour , especially prescribing . Results from previous studies have shown a varying effect . OBJECTIVE The purpose of the study is to examine the effect of academic detailing as a method of implementing a clinical guideline in general practice . METHODS A cluster r and omized , controlled , blinded study was carried out of the effect of an academic detail visit compared with postal distribution of a guideline for prescribing asthma medication . Half the practice s in a Danish county with 100 practice s were visited once . The outcome measure was routinely collected data from all Danish pharmacies on the sales of asthma medication . Data were collected monthly for 2 years before to 1 year after the intervention . RESULTS There was no effect on the pattern of prescription of asthma medicines following the visit , neither immediately nor long term . CONCLUSION We found no effect of academic detailing as a single intervention OBJECTIVE to measure the impact of pharmacist-conducted clinical medication review with elderly care home residents . DESIGN r and omised controlled trial of clinical medication review by a pharmacist against usual care . SETTING sixty-five care homes for the elderly in Leeds , UK . PARTICIPANTS a total of 661 residents aged 65 + years on one or more medicines . INTERVENTION clinical medication review by a pharmacist with patient and clinical records . Recommendations to general practitioner for approval and implementation . Control patients received usual general practitioner care . MAIN OUTCOME MEASURES primary : number of changes in medication per participant . Secondary : number and cost of repeat medicines per participant ; medication review rate ; mortality , falls , hospital admissions , general practitioner consultations , Barthel index , St and ardised Mini-Mental State Examination ( SMMSE ) . RESULTS the pharmacist review ed 315/331 ( 95.2 % ) patients in 6 months . A total of 62/330 ( 18.8 % ) control patients were review ed by their general practitioner . The mean number of drug changes per patient were 3.1 for intervention and 2.4 for control group ( P < 0.0001 ) . There were respectively 0.8 and 1.3 falls per patient ( P < 0.0001 ) . There was no significant difference for GP consultations per patient ( means 2.9 and 2.8 in 6 months , P = 0.5 ) , hospitalisations ( means 0.2 and 0.3 , P = 0.11 ) , deaths ( 51/331 and 48/330 , P = 0.81 ) , Barthel score ( 9.8 and 9.3 , P = 0.06 ) , SMMSE score ( 13.9 and 13.8 , P = 0.62 ) , number and cost of drugs per patient ( 6.7 and 6.9 , P = 0.5 ) ( pounds sterling 42.24 and pounds sterling 42.94 per 28 days ) . A total of 75.6 % ( 565/747 ) of pharmacist recommendations were accepted by the general practitioner ; and 76.6 % ( 433/565 ) of accepted recommendations were implemented . CONCLUSIONS general practitioners do not review most care home patients ' medication . A clinical pharmacist can review them and make recommendations that are usually accepted . This leads to substantial change in patients ' medication regimens without change in drug costs . There is a reduction in the number of falls . There is no significant change in consultations , hospitalisation , mortality , SMMSE or Barthel scores OBJECTIVE The purpose of this study was to assess the impacts of individualized prescribing feedback and interactive small group education aim ed at encouraging evidence -based prescribing in family/general practice . METHODS A two-by-two factorial r and omized controlled trial was carried out involving 200 family physicians in British Columbia , Canada . The physicians met monthly in 28 peer learning groups within the Practice -Based Small Group ( PBSG ) learning programme . Personalized prescribing feedback related to hypertension was provided through ' prescribing portraits ' which graphically displayed comparative rates of individual and peer group prescribing , together with a concise guide for evidence -based prescribing . A case-based educational module , containing the same evidence -based message , was discussed in small groups . Groups were matched and r and omized into four arms of seven groups each : control ( n = 56 ) , prescribing portrait only ( n = 48 ) , educational module only ( n = 47 ) , both portrait and module ( n = 49 ) . The main outcome measure was changes in ' prescribing preferences ' to new patients among those medications used to treat hypertension ( i.e. probability that a patient would receive the evidence -based medication as first-line therapy ) . RESULTS Using data from the provincial pharmacy registry ( PharmaNet ) , prescribing preferences for antihypertensive agents were determined for all groups for a 6 month period before and after the interventions , based on 4394 patients receiving a first-line antihypertensive . Significant absolute increases in prescribing preference for thiazides were documented for both the module + 0.068 ( confidence interval [ CI ] 0.022 - 0.115 ) and the portrait + 0.065 ( CI 0.018 - 0.111 ) . Preference in the group receiving both module and portrait increased by + 0.115 ( CI 0.040 - 0.189 ) . CONCLUSIONS Evidence -based educational interventions combining personalized prescribing feedback with interactive group discussion can lead to modest but meaningful changes in physician prescribing . Clear messages , proper trial design and sensitive outcomes are necessary to demonstrate these changes Objective : To determine whether an educational intervention aim ed at parents leads to fewer antibiotic prescriptions for their children . Design : Placebo-controlled , r and omized controlled trial . Setting : Offices of primary care pediatricians who are members of a regional practice -based research network . Participants : Healthy children younger than 24 months old enrolled at the time of an office visit . Interventions : Parents of study children were r and omized to receive either a pamphlet and videotape ( featuring one of their child 's pediatricians ) promoting the judicious use of antibiotics ( intervention group ) or brochures about injury prevention ( control group ) . A total of 499 eligible children were enrolled , and data on outpatient visits during a 12-month observation period were collected . Main Outcome Measures : We compared the number of visits for upper respiratory tract infections ( URIs ) , number of diagnoses and antibiotic prescriptions for otitis media and /or sinusitis and total number of antibiotics per patient among children in the intervention and control groups using Poisson regression analysis , adjusted for clustering into different practice s. Results : Data on 4924 visits were review ed ; 28.8 % of these visits were because of URI symptoms . The mean number of visits per study patient for URI symptoms was 2.8 . Including all visits , the mean number of diagnoses of otitis media in study children was 2.1 , mean number of diagnoses of otitis media and /or sinusitis was 2.3 and mean number of antibiotic prescriptions was 2.4 ; there were no significant differences between children in the intervention and control groups for any of these outcomes . Overall physicians prescribed 1 or more antibiotics during 45.9 % of visits for a chief complaint of URI symptoms ; 92 % of antibiotic usage in children presenting with URI symptoms was for a diagnosis of otitis media and /or sinusitis . Conclusions : An educational intervention aim ed at parents did not result in a decrease in the number of antibiotic prescriptions in their children . The use of antibiotics among children with URI symptoms was common ; other interventions promoting the judicious use of these medications are needed THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard BACKGROUND Interventions to promote prescribing of preventive therapies in patients with cardiovascular disease ( CVD ) or diabetes have reported variable success . OBJECTIVE ( i ) To evaluate the effect of prescribing feedback on GP practice using academic detailing compared to postal bulletin on prescribing of CVD preventive therapies in patients with CVD or diabetes at 3 and 6 months post intervention and ( ii ) to evaluate the intervention from a GP 's perspective . METHODS Volunteer GP practice s ( n = 98 ) were r and omized to receive individualized prescribing feedback via academic detailing ( postal bulletin plus outreach visit ) ( n = 48 ) or postal bulletin ( n = 50 ) . The proportion of CVD or diabetic patients on statins and antiplatelet agents/warfarin pre- and post-intervention was calculated for each GP practice . Multivariate regression with a r and om effects model was used to compare differences between the groups adjusting for GP clustering and confounding factors . beta-Coefficients and 95 % confidence intervals ( CIs ) are presented . RESULTS There was a 3 % increase in statin prescribing in CVD patients at 6 months post-intervention for both r and omized groups , but there was no statistical difference between the groups ( beta = 0.004 ; 95 % CI = -0.01 to 0.02 ) . Statin and antiplatelet/warfarin prescribing also increased in the diabetic population ; there was no significant differences between the groups . GPs participating in the project expressed a high level of satisfaction with both interventions . CONCLUSION Prescribing of preventive therapies increased in both r and omized groups over the study period . But academic detailing did not have an additional effect on changing prescribing over the postal bulletin alone |
2,179 | 32,013,780 | Conclusion : Almost all domains were addressed across all interventions currently offered for this population to various degrees , but not within a singular intervention . | Background : People with dementia requiring palliative care have multiple needs , which are amplified in long-term care setting s. The European Association for Palliative Care White Paper offers recommendations for optimal palliative care in dementia integral for this population , providing useful guidance to inform interventions addressing their specific needs .
Aim : The aim of this study is to describe the components of palliative care interventions for people with dementia in long-term care focusing on shared decision-making and examine their alignment to the European Association for Palliative Care domains of care . | Background Palliative care planning for nursing home residents with advanced dementia is often suboptimal . This study compared effects of facilitated case conferencing ( FCC ) with usual care ( UC ) on end-of-life care . Methods A two arm parallel cluster r and omised controlled trial was conducted . The sample included people with advanced dementia from 20 Australian nursing homes and their families and professional caregivers . In each intervention nursing home ( n = 10 ) , Palliative Care Planning Coordinators ( PCPCs ) facilitated family case conferences and trained staff in person-centred palliative care for 16 hours per week over 18 months . The primary outcome was family-rated quality of end-of-life care ( End-of-Life Dementia [ EOLD ] Scales ) . Secondary outcomes included nurse-rated EOLD scales , resident quality of life ( Quality of Life in Late-stage Dementia [ QUALID ] ) and quality of care over the last month of life ( pharmacological/non-pharmacological palliative strategies , hospitalization or inappropriate interventions ) . Results Two-hundred-eighty-six people with advanced dementia took part but only 131 died ( 64 in UC and 67 in FCC which was fewer than anticipated ) , rendering the primary analysis under-powered with no group effect seen in EOLD scales . Significant differences in pharmacological ( P < 0.01 ) and non-pharmacological ( P < 0.05 ) palliative management in last month of life were seen . Intercurrent illness was associated with lower family-rated EOLD Satisfaction with Care ( coefficient 2.97 , P < 0.05 ) and lower staff-rated EOLD Comfort Assessment with Dying ( coefficient 4.37 , P < 0.01 ) . Per protocol analyses showed positive relationships between EOLD and staff hours to bed ratios , proportion of residents with dementia and staff attitudes . Conclusion FCC facilitates a palliative approach to care . Future trials of case conferencing should consider outcomes and processes regarding decision making and planning for anticipated events and acute illness . Trial registration Australian New Zeal and Clinical Trial Registry PURPOSE OF STUDY Dementia affects more than 5 million Americans , and is a leading cause of death . Family members of nursing home ( NH ) residents with advanced dementia report difficulty making decisions about care toward the end of life . As part of a r and omized trial testing an intervention to improve decision making , this qualitative study aim ed to underst and how family decision makers experienced goal -based decision making in advance of the death of their relative . DESIGN AND METHODS This qualitative study was conducted as part of the goals of care clinical trial . Study participants ( n = 16 ) were family decision makers in North Carolina whose relative with advanced dementia died after participating in the goals of care intervention . Semi-structured interviews were analyzed using a qualitative description approach . RESULTS Family members ' experience of decision making and death differed based on the presence or absence of trusting relationships with NH staff . Family members who reported trust described a positive end-of-life experience and less need for prescribed goals of care discussion s. In the absence of trust , family members reported that goals of care discussion s were ignored by staff or created confusion . IMPLICATION S Among family members of persons who recently died from dementia in NHs , expressions of trust in staff were strongly related to perceptions of decision making about goals of care . Although goals of care discussion s may potentially promote communication to earn trust , the presence of pre-existing trust ultimately influenced the decision making and end-of-life experiences of residents and families Background : In dementia care , a large number of treatment decisions are made by family carers on behalf of their family member who lacks decisional capacity ; advance care planning can support such carers in the decision-making of care goals . However , given the relative importance of advance care planning in dementia care , the prevalence of advance care planning in dementia care is poor . Aim : To evaluate the effectiveness of advance care planning with family carers in dementia care homes . Design : Paired cluster r and omized controlled trial . The intervention comprised a trained facilitator , family education , family meetings , documentation of advance care planning decisions and intervention orientation for general practitioners and nursing home staff . Setting / participants : A total of 24 nursing homes with a dementia nursing category located in Northern Irel and , United Kingdom . Family carers of nursing home residents classified as having dementia and judged as not having decisional capacity to participate in advance care planning discussion s. Results : The primary outcome was family carer uncertainty in decision-making about the care of the resident ( Decisional Conflict Scale ) . There was evidence of a reduction in total Decisional Conflict Scale score in the intervention group compared with the usual care group ( −10.5 , 95 % confidence interval : −16.4 to −4.7 ; p < 0.001 ) . Conclusion : Advance care planning was effective in reducing family carer uncertainty in decision-making concerning the care of their family member and improving perceptions of quality of care in nursing homes . Given the global significance of dementia , the implication s for clinicians and policy makers include them recognizing the importance of family carer education and improving communication between family carers and formal care providers Background : Increasing number of people are dying with advanced dementia . Comfort and quality of life are key goals of care . Aims : To describe ( 1 ) physical and psychological symptoms , ( 2 ) health and social care service utilisation and ( 3 ) care at end of life in people with advanced dementia . Design : 9-month prospect i ve cohort study . Setting and participants : Greater London , Engl and , people with advanced dementia ( Functional Assessment Staging Scale 6e and above ) from 14 nursing homes or their own homes . Main outcome measures : At study entry and monthly : prescriptions , Charlson Comorbidity Index , pressure sore risk/severity ( Waterlow Scale/Stirling Scale , respectively ) , acute medical events , pain ( Pain Assessment in Advanced Dementia ) , neuropsychiatric symptoms ( Neuropsychiatric Inventory ) , quality of life ( Quality of Life in Late-Stage Dementia Scale ) , re source use ( Re source Utilization in Dementia Question naire and Client Services Receipt Inventory ) , presence/type of advance care plans , interventions , mortality , place of death and comfort ( Symptom Management at End of Life in Dementia Scale ) . Results : Of 159 potential participants , 85 were recruited ( 62 % alive at end of follow-up ) . Pain ( 11 % at rest , 61 % on movement ) and significant agitation ( 54 % ) were common and persistent . Aspiration , dyspnoea , septicaemia and pneumonia were more frequent in those who died . In total , 76 % had ‘ do not resuscitate ’ statements , less than 40 % advance care plans . Most received primary care visits , there was little input from geriatrics or mental health but contact with emergency paramedics was common . Conclusion : People with advanced dementia lived with distressing symptoms . Service provision was not tailored to their needs . Longitudinal multidisciplinary input could optimise symptom control and quality of life Background : Despite increased attention for palliative care in dementia , recent studies found burdensome symptoms and unmet family caregiver needs in the last phase of life . Feedback is being used to improve the quality of palliative care , but we do not know how effective it is . Aim : To assess the effect of two feedback strategies on perceived quality of end-of-life care and comfort in dying nursing home residents with dementia . Methods : In a cluster-r and omized controlled trial , the End-of-Life in Dementia – Satisfaction With Care and the End-of-Life in Dementia – Comfort Assessment in Dying scales were completed by bereaved family caregivers of residents with dementia of 18 Dutch nursing homes . Two feedback strategies , generic feedback with mean End-of-Life in Dementia-scores and feedback with individual ( patient-specific ) End-of-Life in Dementia-scores , were compared to no feedback provided . The intervention groups discussed End-of-Life in Dementia-ratings in team meetings and formulated actions to improve care . Multi-level analyses assessed effects . Results : A total of 668 families rated the End-of-Life in Dementia – instruments . Compared to no feedback , the generic strategy result ed in lower quality of end-of-life care in unadjusted ( B = −1.65 , confidence interval = −3.27 ; −0.21 ) and adjusted analyses ( B = −2.41 , confidence interval = −4.07 ; −0.76 ) , while there was no effect on comfort . The patient-specific strategy did not affect the quality of end-of-life care , but it increased comfort in unadjusted analyses ( only , B = 2.20 , confidence interval = 0.15 ; 4.39 ; adjusted : B = 1.88 , confidence interval = −0.34 ; 4.10 ) . Conclusion : Neither feedback strategy improved end-of-life outcome . Perhaps , skills to translate the feedback into care improvement actions were insufficient . Feedback with favorable family ratings might even have triggered opposite effects . Trial number : NTR3942 BACKGROUND Increasing numbers of older people with advanced dementia are cared for in care homes . No cure is available , so research focused on improving quality of life and quality of care for people with dementia is needed to support them to live and die well . The Namaste Care programme is a multi-dimensional care program with sensory , psycho-social and spiritual components intended to enhance quality of life and quality of care for people with advanced dementia . The aim of the study was to establish whether the Namaste Care program can be implemented in UK care homes ; and what effect Namaste Care has on the quality of life of residents with advanced dementia , their families and staff . This article explores the qualitative findings of the study , reporting the effect of the programme on the families of people with advanced dementia and care home staff , and presenting their perceptions of change in care . METHODS An organisational action research methodology was used . Focus groups and interviews were undertaken pre/post implementation of the Namaste Care program . The research er kept a reflective diary recording data on the process of change . A comments book was available to staff and relatives in each care home . Data was analysed thematically within each care home and then across all care homes . RESULTS Six care homes were recruited in south London : one withdrew before the study was underway . Of the five remaining care homes , four achieved a full Namaste Care program . One care home did not achieve the full program during the study , and another discontinued Namaste Care when the study ended . Every home experienced management disruption during the study . Namaste Care challenged normal routinised care for older people with advanced dementia . The characteristics of care uncovered before Namaste was implemented were : chaos and confusion , rushing around , lack of trust , and rewarding care . After the programme was implemented these perceptions were transformed , and themes of calmness , reaching out to each other , seeing the person , and , enhanced well-being , emerged . CONCLUSIONS Namaste Care can enrich the quality of life of older people with advanced dementia in care homes . The program was welcomed by care home staff and families , and was achieved with only modest expenditure and no change in staffing levels . The positive impact on residents quality of life influenced the well-being of family carers . Care staff found the changes in care enjoyable and rewarding . Namaste Care was valued for the benefits seen in residents ; the improvement in relationships ; and the shift towards a person-centred , relationship-based culture of care brought about by introducing the program . Namaste Care deserves further exploration and investigation including a r and omised controlled trial People with dementia have often been excluded from pain studies . However , there is evidence supporting that people with dementia experience frequent pain , often poorly assessed and undertreated , and that the etiology for pain descriptions is poorly documented . The Assessment of Discomfort in Dementia ( ADD ) Protocol is design ed to : a ) more accurately assess discomfort in people with dementia who can no longer verbally describe physical pain or affective discomfort ; b ) more accurately and thoroughly treat physical pain and affective discomfort ; and c ) decrease inappropriate use of psychotropic medication . The use of the ADD Protocol was studies with a convenience sample of 104 residents of long-term care with end-stage dementia . Use of the ADD Protocol was associated with a significant decrease in discomfort ( t = 6.56 , p = 0.000 ) . The most frequently seen behavioral symptoms associated with discomfort were tense body language , sad facial expression , fidgeting , perseverant verbalizations , and verbal outburts . The ADD Protocol was also associated with a significant increase in the use of scheduled analgesics and non-pharmacological comfort interventions . The protocol was not associated with an increase in the use of prn analgesics or with prn or scheduled psychotropics . This study has provided some support for the notion that the needs of people with significant dementia can be discerned and treated OBJECTIVES To test whether a decision aid improves quality of decision-making about feeding options in advanced dementia . DESIGN Cluster r and omized controlled trial . SETTING Twenty-four nursing homes in North Carolina . PARTICIPANTS Residents with advanced dementia and feeding problems and their surrogates . INTERVENTION Intervention surrogates received an audio or print decision aid on feeding options in advanced dementia . Controls received usual care . MEASUREMENTS Primary outcome was the Decisional Conflict Scale ( range : 1 - 5 ) measured at 3 months ; other main outcomes were surrogate knowledge , frequency of communication with providers , and feeding treatment use . RESULTS Two hundred fifty-six residents and surrogate decision-makers were recruited . Residents ' average age was 85 ; 67 % were Caucasian , and 79 % were women . Surrogates ' average age was 59 ; 67 % were Caucasian , and 70 % were residents ' children . The intervention improved knowledge scores ( 16.8 vs 15.1 , P < .001 ) . After 3 months , intervention surrogates had lower Decisional Conflict Scale scores than controls ( 1.65 vs 1.90 , P < .001 ) and more often discussed feeding options with a healthcare provider ( 46 % vs 33 % , P = .04 ) . Residents in the intervention group were more likely to receive a dysphagia diet ( 89 % vs 76 % , P = .04 ) and showed a trend toward greater staff eating assistance ( 20 % vs 10 % , P = .08 ) . Tube feeding was rare in both groups even after 9 months ( 1 intervention vs 3 control , P = .34 ) . CONCLUSION A decision aid about feeding options in advanced dementia reduced decisional conflict for surrogates and increased their knowledge and communication about feeding options with providers Background Pneumonia in people with dementia has been associated with severe discomfort . We sought to assess the effectiveness of a practice guideline for optimal symptom relief for nursing home residents with dementia and pneumonia . Methods A single-blind , multicenter , cluster r and omized controlled trial was conducted in 32 Dutch nursing homes . Outcomes were assessed on the patient level . The main outcome measures were discomfort and symptoms : discomfort ( DS-DAT : Discomfort Scale-Dementia of Alzheimer Type ) , ( lack of ) comfort ( EOLD-CAD : End Of Life in Dementia-Comfort Assessment in Dying ) , pain ( PAINAD : Pain Assessment in Advanced Dementia ) , and respiratory distress ( RDOS : Respiratory Distress Observation Scale ) . Outcomes were scheduled daily from diagnosis until 10 days later and a final time between 13–15 days from diagnosis by trained observers who were blinded to the intervention and the residents ’ condition and treatment . In a pre-intervention phase , usual care was provided to all homes . In the intervention phase , matched clusters of homes were r and omized to either the control ( n = 16 ) or intervention condition ( n = 16 ) . Results Between 1 January 2012 and 1 May 2015 , 464 episodes of pneumonia were included . Outcomes were obtained for 399 episodes in 367 residents . Longitudinal multilevel linear regression analyses were performed on log-transformed outcomes , so coefficients should be interpreted as a ratio , and a coefficient of 1 means no difference . The practice guideline in the intervention phase did not reduce the level of discomfort and symptoms : DS-DAT : 1.11 ( 95 % CI 0.93–1.31 ) , EOLD-CAD : 1.01 ( 95 % CI 0.98–1.05 ) , PAINAD : 1.04 ( 95 % CI 0.93–1.15 ) , RDOS : 1.11 ( 95 % CI 0.90–1.24 ) . However , in both the intervention and control groups , lack of comfort and respiratory distress gradually decreased during the entire 3.5 years of data collection , and were lower in the intervention phase compared to the pre-intervention phase : DS-DAT : 0.93 ( 95 % CI 0.85–1.01 ) , EOLD-CAD : 0.98 ( 95 % CI 0.97–1.00 ) , PAINAD : 0.96 ( 95 % CI 0.91–1.01 ) , RDOS : 0.92 ( 95 % CI 0.87–0.98 ) . Conclusions When compared to usual care , the practice guideline for optimal symptom relief did not relieve discomfort and symptoms in nursing home residents with dementia and pneumonia . However , discomfort and symptoms decreased gradually throughout the data collection in both the intervention homes and the control homes . An intervention that focuses on creating awareness may be more effective than a physician practice guideline .Trial registration The Netherl and s National Trial Register ( ID number NTR5071 . Registered 10 March 2015 ) Introduction In the UK approximately 700 000 people are living with , and a third of people aged over 65 will die with , dementia . People with dementia may receive poor quality care towards the end of life . We applied a realist approach and used mixed methods to develop a complex intervention to improve care for people with advanced dementia and their family carers . Consensus on intervention content was achieved using the R AND UCLA appropriateness method and mapped to sociological theories of process and impact . Core components are : ( 1 ) facilitation of integrated care , ( 2 ) education , training and support , ( 3 ) investment from commissioners and care providers . We present the protocol for an exploratory phase I study to implement components 1 and 2 in order to underst and how the intervention operates in practice and to assess feasibility and acceptability . Methods and analysis An ‘ Interdisciplinary Care Leader ( ICL ) ’ will work within two care homes , alongside staff and associated professionals to facilitate service integration , encourage structured needs assessment , develop the use of personal and advance care plans and support staff training . We will use qualitative and quantitative methods to collect data for a range of outcome and process measures to detect effects on individual residents , family carers , care home staff , the intervention team , the interdisciplinary team and wider systems . Analysis will include descriptive statistics summarising process and care home level data , individual demographic and clinical characteristics and data on symptom burden , clinical events and quality of care . Qualitative data will be explored using thematic analysis . Findings will inform a future phase II trial . Ethics and dissemination Ethical approval was granted ( REC reference 14/LO/0370 ) . We shall publish findings at conferences , in peer- review ed journals , on the Marie Curie Cancer Care website and prepare reports for dissemination by organisations involved with end-of-life care and dementia BACKGROUND One in three adults , most of whom are living in a care home at the time , dies with dementia . Their end-of-life is often in hospital , where they may experience uncomfortable interventions without known benefit and die rapidly with uncontrolled pain and comfort needs . This study aim ed to improve end-of-life care for people with dementia in a care home by increasing the number and implementation of advanced care wishes . METHODS We recruited staff , residents with dementia , and their relatives from a 120-bed nursing home in London , UK . The intervention was a ten-session manualized , interactive staff training program . We compared advance care wishes documentation and implementation , place of death for residents who died , and themes from staff and family carers ' after-death interviews pre- and post-intervention . RESULTS Post-intervention there were significant increases in documented advance care wishes arising from residents ' and relatives ' discussion s with staff about end-of-life . These included do not resuscitate orders ( 16/22 , 73 % vs. 4/28 , 14 % ; p < 0.001 ) ; and dying in the care homes as opposed to hospital ( 22/29 , 76 % vs. 14/30 , 47 % ; p < 0.02 ) . Bereaved relatives overall satisfaction increased from 7.5 ( SD = 1.3 ) pre-intervention to 9.1 ( SD = 2.4 ) post-intervention ; t = 17.6 , p = 0.06 . Relatives reported increased consultation and satisfaction about decisions . Staff members were more confident about end-of-life planning and implementing advanced wishes . CONCLUSION This small non-r and omized study is the first end-of-life care in dementia intervention to report an increase in family satisfaction with a reduction in hospital deaths . This is promising but requires further evaluation in diverse care homes OBJECTIVES Decision aids are effective to improve decision-making , yet they are rarely tested in nursing homes ( NHs ) . Study objectives were to ( 1 ) examine the feasibility of a goals of care ( GOC ) decision aid for surrogate decision-makers ( SDMs ) of persons with dementia ; and ( 2 ) to test its effect on quality of communication and decision-making . DESIGN Pre-post intervention to test a GOC decision aid intervention for SDMs for persons with dementia in NHs . Investigators collected data from review s of resident health records and interviews with SDMs at baseline and 3-month follow-up . SETTING Two NHs in North Carolina . PARTICIPANTS Eighteen residents who were over 65 years of age , had moderate to severe dementia on the global deterioration scale ( 5 , 6 , or 7 ) , and an English-speaking surrogate decision-maker . INTERVENTION ( 1 ) GOC decision aid video viewed by the SDM and ( 2 ) a structured care plan meeting between the SDM and interdisciplinary NH team . MEASUREMENTS Surrogate knowledge , quality of communication with health care providers , surrogate-provider concordance on goals of care , and palliative care domains addressed in the care plan . RESULTS Eighty-nine percent of the SDMs thought the decision aid was relevant to their needs . After viewing the video decision aid , SDMs increased the number of correct responses on knowledge-based questions ( 12.5 vs 14.2 ; P < .001 ) . At 3 months , they reported improved quality of communication scores ( 6.1 vs 6.8 ; P = .01 ) and improved concordance on primary goal of care with NH team ( 50 % vs 78 % ; P = .003 ) . The number of palliative care domains addressed in the care plan increased ( 1.8 vs 4.3 ; P < .001 ) . CONCLUSIONS The decision-support intervention piloted in this study was feasible and relevant for surrogate decision-makers of persons with advanced dementia in NHs , and it improved quality of communication between SDM and NH providers . A larger r and omized clinical trial is underway to provide further evidence of the effects of this decision aid intervention Importance In advanced dementia , goals of care decisions are challenging and medical care is often more intensive than desired . Objective To test a goals of care ( GOC ) decision aid intervention to improve quality of communication and palliative care for nursing home residents with advanced dementia . Design , Setting , and Participants A single-blind cluster r and omized clinical trial , including 302 residents with advanced dementia and their family decision makers in 22 nursing homes . Interventions A GOC video decision aid plus a structured discussion with nursing home health care providers ; attention control with an informational video and usual care planning . Main Outcomes and Measures Primary outcomes at 3 months were quality of communication ( QOC , question naire scored 0 - 10 with higher ratings indicating better quality ) , family report of concordance with clinicians on the primary goal of care ( endorsing same goal as the “ best goal to guide care and medical treatment , ” and clinicians ’ “ top priority for care and medical treatment ” ) , and treatment consistent with preferences ( Advance Care Planning Problem score ) . Secondary outcomes at 9 months were family ratings of symptom management and care , palliative care domains in care plans , Medical Orders for Scope of Treatment ( MOST ) completion , and hospital transfers . Resident-family dyads were the primary unit of analysis , and all analyses used intention-to-treat assignment . Results Residents ’ mean age was 86.5 years , 39 ( 12.9 % ) were African American , and 246 ( 81.5 % ) were women . With the GOC intervention , family decision makers reported better quality of communication ( QOC , 6.0 vs 5.6 ; P = .05 ) and better end-of-life communication ( QOC end-of-life subscale , 3.7 vs 3.0 ; P = .02 ) . Goal concordance did not differ at 3 months , but family decision makers with the intervention reported greater concordance by 9 months or death ( 133 [ 88.4 % ] vs 108 [ 71.2 % ] , P = .001 ) . Family ratings of treatment consistent with preferences , symptom management , and quality of care did not differ . Residents in the intervention group had more palliative care content in treatment plans ( 5.6 vs 4.7 , P = .02 ) , MOST order sets ( 35 % vs 16 % , P = .05 ) , and half as many hospital transfers ( 0.078 vs 0.163 per 90 person-days ; RR , 0.47 ; 95 % CI , 0.26 - 0.88 ) . Survival at 9 months was unaffected ( adjusted hazard ratio [ aHR ] , 0.76 ; 95 % CI , 0.54 - 1.08 ; P = .13 ) . Conclusions and Relevance The GOC decision aid intervention is effective to improve end-of-life communication for nursing home residents with advanced dementia and enhance palliative care plans while reducing hospital transfers . Trial Registration clinical trials.gov Identifier : Background Care for people with advanced dementia requires a palliative approach targeted to the illness trajectory and tailored to individual needs . However , care in nursing homes is often compromised by poor communication and limited staff expertise . This paper reports the protocol for the IDEAL Project , which aims to : 1 ) compare the efficacy of a facilitated approach to family case conferencing with usual care ; 2 ) provide insights into nursing home- and staff-related processes influencing the implementation and sustainability of case conferencing ; and 3 ) evaluate cost-effectiveness . Design / Methods A pragmatic parallel cluster r and omised controlled trial design will be used . Twenty Australian nursing homes will be r and omised to receive either facilitated family case conferencing or usual care . In the intervention arm , we will train registered nurses at each nursing home to work as Palliative Care Planning Coordinators ( PCPCs ) 16 h per week over 18 months . The PCPCs ’ role will be to : 1 ) use evidence -based ‘ triggers ’ to identify optimal time-points for case conferencing ; 2 ) organise , facilitate and document case conferences with optimal involvement from family , multi-disciplinary nursing home staff and community health professionals ; 3 ) develop and oversee implementation of palliative care plans ; and 4 ) train other staff in person-centred palliative care . The primary endpoint will be symptom management , comfort and satisfaction with care at the end of life as rated by bereaved family members on the End of Life in Dementia ( EOLD ) Scales . Secondary outcomes will include resident quality of life ( Quality of Life in Late-stage Dementia [ QUALID ] ) , whether a palliative approach is taken ( e.g. hospitalisations , non-palliative medical treatments ) , staff attitudes and knowledge ( Palliative Care for Advanced Dementia [ qPAD ] ) , and cost effectiveness . Processes and factors influencing implementation , outcomes and sustainability will be explored statistically via analysis of intervention ‘ dose ’ and qualitatively via semi-structured interviews . The pragmatic design and complex nature of the intervention will limit blinding and internal validity but support external validity . Discussion The IDEAL Project will make an important contribution to the evidence base for dementia-specific case conferencing in nursing homes by considering processes and context ual factors as well as overall efficacy . Its strengths and weaknesses will both lie in its pragmatic design .Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ACTRN12612001164886 . Registered 02/11/2012 BACKGROUND Palliative care for nursing home residents with advanced dementia is often sub-optimal due to poor communication and limited care planning . In a cluster r and omized controlled trial , registered nurses ( RNs ) from 10 nursing homes were trained and funded to work as Palliative Care Planning Coordinators ( PCPCs ) to organize family case conferences and mentor staff . This qualitative sub- study aim ed to explore PCPC and health professional perceptions of the benefits of facilitated case conferencing and identify factors influencing implementation . METHOD Semi-structured interviews were conducted with the RNs in the PCPC role , other members of nursing home staff , and physicians who participated in case conferences . Analysis was conducted by two research ers using a thematic framework approach . RESULTS Interviews were conducted with 11 PCPCs , 18 other nurses , eight allied health workers , and three physicians . Perceived benefits of facilitated case conferencing included better communication between staff and families , greater multi-disciplinary involvement in case conferences and care planning , and improved staff attitudes and capabilities for dementia palliative care . Key factors influencing implementation included : staffing levels and time ; support from management , staff and physicians ; and positive family feedback . CONCLUSION The facilitated approach explored in this study addressed known barriers to case conferencing . However , current business models in the sector make it difficult for case conferencing to receive the required levels of nursing qualification , training , and time . A collaborative nursing home culture and ongoing relationships with health professionals are also prerequisites for success . Further studies should document resident and family perceptions to harness consumer advocacy Family members of persons with advanced dementia may be asked to make complex treatment decisions without having adequate knowledge regarding the risks and benefits . This 6-month , prospect i ve , r and omized trial tested the effect of an intervention consisting of a face-to-face , structured conversation about end-of-life care options with family members of nursing home residents with advanced dementia . A comparison group received only social contact via telephone . Structured conversations between a palliative care team and intervention group family members included goals of care and how best to achieve those goals , and provision of psychosocial support . Psychosocial support was also provided via telephone at three 2-month intervals . Family members participated in three telephone interviews : baseline , 3 , and 6 months . Specific advance directives for persons with dementia were extracted from medical records . Results showed that intervention families had higher satisfaction with care than comparison families at the 6-month time point , and they were more likely to have decided on medical options listed in residents ' advance directives ( Do Not Resuscitate , Intubate , Hospitalize ) over time . Study findings reinforce the need for increased education and support for families around issues of end-of-life care decisions for advanced dementia Background / aims : Ensuring fidelity to a behavioral intervention implemented in nursing homes requires awareness of the unique considerations of this setting for research . The purpose of this article is to describe the goals of care cluster-r and omized trial and the methods used to monitor and promote fidelity to a goals of care decision aid intervention delivered in nursing homes . Methods : The cluster r and omized trial tested whether a decision aid for goals of care in advanced dementia could improve ( 1 ) the quality of communication and decision-making , ( 2 ) the quality of palliative care , and ( 3 ) the quality of dying for nursing home residents with advanced dementia . In 11 intervention nursing homes , family decision-makers for residents with advanced dementia received a two-component intervention : viewing a video decision aid about goals of care choices and then participating in a structured decision-making discussion with the nursing home care plan team , ideally within 3 months after the decision aid was viewed . Following guidelines from the National Institutes of Health Behavior Change Consortium , fidelity was assessed in study design , in nursing home staff training for intervention implementation , and in monitoring and receipt of the intervention . We also monitored the content and timing of goals of care discussion s. Results : Investigators enrolled 151 family decision-maker/resident dyads in intervention sites ; of those , 136 ( 90 % ) received both components of the intervention , and 92%–99 % of discussion s addressed each of four recommended content areas —health status , goals of care , choice of a goal , and treatment planning . A total of 94 ( 69 % ) of the discussion s between family decision-makers and the nursing home care team were completed within 3 months . Conclusion : The methods we used for intervention fidelity allowed nursing home staff to implement a goals of care decision aid intervention for advanced dementia . Key supports for implementation included design features that aligned with nursing home practice , efficient staff training , and a structured guide for goals of care discussion s between family decision-makers and staff . These approaches may be used to promote fidelity to behavioral interventions in future clinical trials Importance Better advance care planning ( ACP ) can help promote goal -directed care in patients with advanced dementia . Objectives To test whether an ACP video ( vs usual care ) has an effect on documented advance directives , level of care preferences , goals -of-care discussion s , and burdensome treatments among nursing home residents with advanced dementia . Design , Setting , and Participants The Educational Video to Improve Nursing home Care in End-stage dementia ( EVINCE ) trial was a cluster r and omized clinical trial conducted between February 2013 and July 2017 , at 64 Boston-area nursing homes ( 32 facilities per arm ) . A total of 402 residents with advanced dementia and their proxies ( intervention arm , n = 212 ; control arm , n = 190 ) were assessed quarterly for 12 months . Interventions A 12-minute ACP video for proxies with written communication of their preferred level of care ( comfort , basic , or intensive ) to the primary care team . Main Outcomes and Measures The primary outcome was the proportion of residents with do-not-hospitalize ( DNH ) directives by 6 months . Secondary outcomes included preference for comfort care , documented directives to withhold tube-feeding and intravenous hydration , documented goals -of-care discussion s , and burdensome treatments ( hospital transfers , tube-feeding , or parenteral therapy ) per 1000 resident-days . Exploratory analyses examined associations between trial arm and documented advance directives when comfort care was preferred . Results The mean age of the 402 study residents was 86.7 years [ range , 67 - 102 years ] ; 350 were white ( 87.1 % ) and 323 were female ( 80.3 % ) , with DNH directives that by 6 months did not differ between arms ( 63 % in both arms ; adjusted odds ratio [ AOR ] , 1.08 ; 95 % CI , 0.69 - 1.69 ) . Preferences for comfort care , directives to withhold intravenous hydration , and burdensome treatments did not differ between arms . Residents in intervention vs control facilities were more likely to have directives for no tube-feeding at 6 months ( 70.10 % vs 61.90 % ; AOR , 1.79 ; 95 % CI , 1.13 - 2.82 ) and all other time periods , and documented goals -of-care discussion s at 3 months ( 16.10 % vs 7.90 % ; AOR , 2.58 ; 95 % CI , 1.20 - 5.54 ) . When comfort care was preferred , residents in the intervention arm were more likely to have both DNH and no tube-feeding directives ( 72.20 % vs 52.80 % ; AOR , 2.68 ; 95 % CI , 2.68 - 5.85 ) . Conclusions and Relevance An ACP video did not have an effect on preferences , DNH status , or burdensome treatments among residents with advanced dementia , but did increase directives to withhold tube-feeding . When proxies preferred comfort care , advance directives of residents in the intervention arm were more likely to align with that preference . Trial Registration clinical trials.gov Identifier : Introduction Quality of life of people with advanced dementia living in nursing homes is often suboptimal . Family caregivers can feel frustrated with limited contact with their relatives , which results in visits that are perceived as stressful and not very meaningful . Few psychosocial interventions are specifically developed for people with advanced dementia , and actively involve family caregivers or volunteers . Also , interventions usually stop when it becomes difficult for people to participate . The Namaste Care Family programme aims to increase the quality of life of people with advanced dementia , and improve family caregiving experiences through connecting to people and making them comfortable . Methods and analysis Our study will evaluate the effects of the Namaste Care Family programme on quality of life of people with advanced dementia living in nursing homes and family caregiving experiences using a cluster-r and omised controlled trial . Longitudinal analyses will be performed taking into account clustering at the nursing home level . Both a cost-effectiveness and a cost-utility analysis from a societal perspective will be performed . We will modify the Namaste Care Family programme to increase family and volunteer involvement in ongoing and end-of-life care . Data collection involves assessment s by family caregivers , nursing staff and elderly care physicians using question naires , and observations by the research ers at baseline and multiple times over 12 months . The last question naire will be sent up to month 24 after the death of the person with dementia . During semistructured interviews , the feasibility , accessibility and sustainability of the Namaste Care Family programme will be assessed . Ethics and dissemination The study protocol is approved by the Medical Ethics Review Committee of the VU University Medical Center in Amsterdam ( protocol no. 2016.399 ) and registered with the Nederl and s Trial Register ( NTR5692 ) . The findings will be disseminated via publications in peer- review ed journals , conference presentations and presentations for healthcare professionals where appropriate . Trial registration number NTR5692 Introduction Many people living with advanced dementia live and die in nursing care homes . The quality of life , care and dying experienced by these people is variable . Namaste Care is a multisensory programme of care developed for people with advanced dementia . While there is emerging evidence that Namaste Care may be beneficial for people with dementia , there is a need to conduct a feasibility study to establish the optimum way of delivering this complex intervention and whether benefits can be demonstrated in end-of-life care , for individuals and service delivery . The aim of the study is to ascertain the feasibility of conducting a full trial of the Namaste Care intervention . Methods and analysis A feasibility study , comprising a parallel , two-arm , multicentre cluster controlled r and omised trial with embedded process and economic evaluation . Nursing care homes ( total of eight ) who deliver care to those with advanced dementia will be r and omly allocated to intervention ( delivered at nursing care home level ) or control . Three participant groups will be recruited : residents with advanced dementia , informal carers of a participating resident and nursing care home staff . Data will be collected for 6 months . Feasibility objectives concern the recruitment and sampling of nursing homes , residents , informal carers and staff ; the selection and timing of primary ( quality of dying and quality of life ) and secondary clinical outcome measures ( person centredness , symptom presence , agitation , quality of life , re source use and costs and residents ’ activity monitored using actigraphy ) . Acceptability , fidelity and sustainability of the intervention will be assessed using semistructured interviews with staff and informal carers . Ethics and dissemination This protocol has been approved by NHS Wales Research Ethics Committee 5 ( ref : 17/WA0378 ) . Dissemination plans include working with a public involvement panel , through a website ( http://www.namastetrial.org.uk ) , social media , academic and practice conferences and via peer review ed publications . Trial registration number IS RCT N14948133 ; Pre- results Background : Pain in nursing home residents with advanced dementia remains a major challenge ; it is difficult to detect and may be expressed as challenging behavior . STA OP ! aims to identify physical and other needs as causes of behavioral changes and uses a stepwise approach for psychosocial and pharmacological management which was effective in improving challenging behavior . Aim : To assess whether implementation of the stepwise multidisciplinary intervention also reduces pain and improves pain management . Design : In a cluster r and omized controlled trial ( Netherl and s National Trial Register NTR1967 ) , healthcare professionals of intervention units received the stepwise training , while training of the control group focused on knowledge and skills without the stepwise component . Observed and estimated pain was assessed at baseline and at 3 and 6 months post-intervention . Logistic generalized estimating equations were used to test treatment and time effects . Setting / participants : A total of 21 clusters ( single nursing home units ) in 12 Dutch nursing homes included 288 residents with advanced dementia ( Global Deterioration Scale score 5 , 6 , or 7 ) : 148 in the intervention and 140 in the control condition . Results : The multilevel modeling showed an overall effect of the intervention on observed pain but not on estimated pain ; Pain Assessment Checklist for Seniors with Limited Ability to Communicate – Dutch version , mean difference : −1.21 points ( 95 % confidence interval : −2.35 to −0.06 ) ; Minimum Data set of the Resident Assessment Instrument pain scale , mean difference : −0.01 points ( 95 % confidence interval : −0.36 to 0.35 ) . Opioid use increased ( odds ratio = 3.08 ; 95 % confidence interval : 1.08–8.74 ) ; paracetamol use did not ( odds ratio = 1.38 ; 95 % confidence interval : 0.71–2.68 ) . Conclusion : STA OP ! was found to decrease “ observed ” pain but not estimated pain . Observing pain-related behavior might help improve pain management in dementia Background One in four Americans , and 70 % of people who have dementia , will spend their final days in nursing home care . Clinical research , particularly clinical trials , rarely includes this population due to unique challenges in research methods and ethics . Families of advanced dementia patients make choices about tube feeding and other feeding options with limited access to information or communication . The cluster r and omized trial , Improving Decision Making about Feeding Options for Dementia Patients , tests a decision aid intervention to improve the quality of decision making for this choice . Purpose Our objectives are ( 1 ) to describe the methods used in this trial ; ( 2 ) to describe challenges and strategies for effective nursing home and nursing home resident recruitment and retention ; and ( 3 ) to describe research ethics approaches to minimize harms and maximize benefits for this population . Methods The study is a cluster r and omized trial of a decision aid to inform and support the choice between tube feeding and assisted oral feeding in advanced dementia . Study subjects are paired surrogate decision makers and residents with advanced dementia and feeding problems , enrolled from nursing homes in North Carolina . Results This trial enrolled 256 paired surrogate decision makers and residents in 24 nursing home sites , and 99 % completed participation through the 3-month study period . The research team had prior clinical and investigative experience in this setting , and used multiple strategies to recruit and retain nursing home sites , providers , surrogates , and the residents for whom they spoke . Informed consent and human subjects ’ protections were design ed to address the vulnerability of this population . Limitations Cluster r and omization was necessary to avoid contamination between control and intervention subjects , but may introduce confounding by site and intracluster correlation effects in analyses . Conclusions Strategies that facilitate nursing home recruitment , participant recruitment and protection of human subjects for a vulnerable population may be used by future investigators to exp and the research evidence base for nursing home and dementia care . Clinical Trials 2010 ; 7 : 735—743 . http:// |
2,180 | 29,682,305 | Conclusion : Among people who use drugs , directly observed therapy may lead to higher odds of attaining SVR . | Objective : We conducted a meta- analysis of r and omised studies that assessed the effectiveness of directly observed hepatitis C medication therapy delivered in outpatient clinics compared to treatment as usual . | BACKGROUND The diagnosis and treatment of chronic hepatitis C are major concerns in prisons . OBJECTIVES The aim of this r and omized clinical trial was to determine the extent to which directly observed therapy ( DOT ) improved the efficacy of the st and ard treatment for chronic hepatitis C in the prison setting . PATIENTS AND METHODS A r and omized clinical trial was carried out to evaluate the efficacy of a DOT compared with a self-administered therapy in prison inmates who underwent st and ard treatment for chronic hepatitis C ( based on pegylated interferon alpha-2a and ribavirin ) . RESULTS A total of 252 inmates were r and omized , of which 244 were analyzed : 109 in the DOT group and 135 in the non-DOT group . The mean age was 35.88 years ( SD 6.54 ) , 94.3 % were men , 72.1 % reported intravenous drug use , 21.3 % were HIV co-infected , and 55.3 % had genotype 1 or 4 . The patients received the study treatment for a median time of 33.9 weeks in the overall sample . Sustained virological response was achieved in 60.6 % ( 95 % CI , 51.17 - 69.22 ) of the DOT group and in 65.9 % ( 95 % CI , 57.59 - 73.38 ) of the st and ard therapy group ( risk ratio=0.92 ; 95 % CI , 0.76 - 1.12 ) . The mean proportion of patients continuing the treatment was 83 % ( SD=31 ) . Adverse events were reported in 93.4 % of the patients , and serious adverse events were reported in 8.2 % , with no significant differences between groups . CONCLUSIONS Sustained virological response was remarkably high , although there were no differences between groups , probably due to high treatment adherence Introduction People who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population . Methods INTEGRATE was a prospect i ve , observational study investigating the effectiveness , safety , and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin ( Peg-IFN/RBV ) in patients with history of injecting drug use chronically infected with genotype 1 HCV . Results A total of 46 patients were enrolled and included in the intent-to-treat ( ITT ) population . Among heroin and /or cocaine users ( n = 37 ; 80 % ) , 22 % reported use in the past month ; 74 % ( 34/46 ) of patients were on opioid substitution therapy in the pre-treatment phase , and 43 % ( 20/46 ) discontinued HCV treatment prematurely . Sustained virologic response rate was 54 % ( 25/46 ) in the ITT population and 74 % ( 25/34 ) in the per protocol ( evaluable-for-effectiveness ) population . The main reason for failure in the ITT analysis was loss to follow-up ( n = 8 ; 17 % ) . Adverse events occurred in 91 % ( 42/46 ) of patients . Mean patient-reported adherence to study drugs was > 89 % at Week 4 , Week 12 and end of treatment . Conclusion Despite a high rate of treatment discontinuation ( including loss to follow-up ) , self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts . Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection , and highlight the need for improvements in patient support to boost retention in care and , in turn , help to prevent reinfection and transmission . Clinical trial registration Clinical trials.gov identifier , NCT01980290 . Funding Janssen Pharmaceuticals Background : Hepatitis C virus ( HCV ) is a prevalent chronic blood-borne infection among opioid-dependent patients on methadone maintenance treatment ( MMT ) . Despite case reports and case – control studies , a r and omized controlled trial ( RCT ) examining HCV treatment adherence in methadone-maintained patients is lacking and was the impetus for this ongoing RCT examining modified directly administered therapy for HCV treatment integrated within a MMT . Methods : Subjects were r and omized 1:1 to receive HCV treatment as modified directly observed therapy ( mDOT ) into the MMT program or at a liver specialty clinic as self-administered therapy ( SAT ) . R and omization was stratified based on HIV status and HCV genotype . Results : Twenty-one subjects to date have enrolled in this pilot study . The mDOT subjects have had greater success in starting treatment and 10 of the 12 mDOT subjects achieved early virologic response ( EVR ) at week 12 and 6 of those 10 achieved sustained virologic response ( SVR ) . Of the nine SAT subjects , only three achieved EVR at week 12 and only one achieved SVR despite not completing the treatment . Conclusions : Hepatitis C treatment can be successfully integrated into a methadone maintenance clinic , and mDOT can be implemented with a methadone clinic ’s existing nursing and medical staff . Patients struggling with concurrent substance use and mental illness comorbidity may be successfully addressed in such setting s and facilitate access to and completion of treatment through the utilization of on-site clinical services for HCV treatment and adherence support with mDOT . The exact importance of site of services and adherence support remains a significant area for future investigation BACKGROUND This study investigated the efficacy and safety of directly observed pegylated interferon ( peg-IFN ) alfa-2a plus self-administered ribavirin ( RBV ) for the treatment of hepatitis C virus ( HCV ) among people with active drug use . METHODS A r and omized , open-label , parallel group trial of immediate vs delayed treatment with peg-IFN alfa-2a plus RBV in participants with recent injection drug and /or crack cocaine use ( prior 3 months ) . The primary end point was sustained virologic response ( SVR ) . RESULTS Sixty-six participants were r and omized ( immediate treatment , n = 48 ; delayed treatment , n = 18 ) . Loss to follow-up was comparable among those r and omized to immediate and delayed treatment ( 23 % vs 33 % , P = .389 ) . In a post hoc intent-to-treat analysis of all r and omized individuals , the SVR was 65 % ( 95 % confidence interval [ CI ] , 49%-78 % ; 31/48 ) in those r and omized to immediate treatment as compared to 39 % ( 95 % CI , 17%-64 % ; 7/18 ) in those r and omized to delayed treatment ( P = .060 ) . Among those who received delayed treatment ( 12/18 ) , SVR was 58 % ( 7/12 ) . Among 60 participants who received at least 1 dose of study medication , SVR was 63 % ( 95 % CI , 50%-75 % , n = 38 ) . Recent drug use at baseline ( past month ) did not impact completion or SVR . Discontinuation due to adverse events occurred in 7 % . The HCV reinfection rate was 2.8 per 100 person-years ( 95 % CI , 0.0 - 14.5 person-years ) with 1 reinfection observed among 23 remaining in follow-up post-SVR ( median , 1.8 years ; range , 0.5 - 1.8 years ) . CONCLUSIONS Among people actively using drugs treated with directly observed peg-IFN alfa-2a plus self-administered RBV , SVR is comparable to that seen in clinical trials of non-drug users , and the rate of HCV reinfection is low Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies BACKGROUND Direct-acting antiviral therapy ( DAAs ) for hepatitis C infection ( HCV ) have a much smaller burden of treatment than interferon-based regimes , require less monitoring and are very effective . New pathways are required to increase access to treatment amongst people prescribed opioid substitution therapy ( OST ) . METHODS An exploratory cluster r and omised controlled trial with mixed methods evaluation was undertaken to compare the uptake of dried blood spot testing ( DBST ) and treatment of people with genotype 1 HCV infection in a conventional service pathway versus a pharmacist-led pathway in a population receiving OST . RESULTS Pharmacies r and omised to the conventional pathway obtained 58 DBST from 244 patients (24%):15 new reactive tests and 33 new negative tests were identified . Within the pharmacist-led pathway , 94 DBST were obtained from 262 patients ( 36 % ) : 26 new reactive tests and 54 new negative tests were identified . Participants in the pharmacist-led pathway were more likely to take a DBST ( p<0.003 ) . Of participants referred for treatment through the conventional pathway , 4 patients from 15 with new reactive tests ( 27 % ) attended clinic for assessment . In the pharmacist-led treatment pathway , 20 patients from 26 with new reactive tests ( 77 % ) attended for assessment blood tests . Participants in the pharmacist-led pathway were more likely to proceed through the assessment for treatment ( p<0.002 ) . One participant completed treatment through the conventional pathway and three patients completed treatment through the pharmacist-led pathway . The process evaluation identified key themes important to service user completers and staff participants . CONCLUSION The study provides evidence that testing and treatment for HCV in a pharmacist led-pathway is a feasible treatment pathway for people who receive supervised OST consumption through community pharmacies . This feasibility trial therefore provides sufficient confirmation to justify proceeding to a full trial BACKGROUND : Adherence to chronic hepatitis C ( CHC ) treatment may be particularly challenging in methadone maintenance patients . We assessed the safety , tolerability , and efficacy of peginterferon alfa-2a/ribavirin treatment in methadone maintenance patients previously untreated for CHC . METHODS : Patients were r and omized 1:1 to direct observed therapy ( DOT ) or self-administration ( SA ) of peginterferon alfa-2a . DOT patients were seen weekly at methadone clinics ; SA patients were seen less frequently , only at investigative sites . Genotype 1-infected patients were treated for 48 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 1,000/1,200 mg/day ) ; genotypes 2- and 3-infected patients were treated for 24 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 800 mg/day ) . RESULTS : Based on defined efficacy stopping rules , 77 % ( 37/48 ) completed their targeted length of treatment , and 44 % ( 21/48 ) achieved sustained virologic response ( SVR ) . Two DOT and 3 SA patients were withdrawn for safety reasons and 6 and 9 , respectively , for nonsafety reasons . Over 60 % and 50 % of each group were > 80 % compliant with the planned cumulative doses of peginterferon alfa-2a and ribavirin , respectively , and over 60 % with overall treatment duration . SVR rates were 54 % ( 13/24 ) for DOT and 33 % ( 8/24 ) for SA ; 23 % ( 3/13 ) and 38 % ( 6/16 ) , respectively , for genotype 1 and 91 % ( 10/11 ) and 25 % ( 2/8 ) , respectively , for genotypes 2 and 3 . Stepwise logistic regression analysis , showed that DOT ( vs SA ; OR 3.27 , 95 % CI 0.90–11.91 , P= 0.073 ) and Caucasian race ( vs Other ; OR 13.31 , 95 % CI 1.42–124.71 , P= 0.023 ) were predictors of SVR . CONCLUSION : Peginterferon alfa-2a/ribavirin can be used safely and successfully in CHC patients receiving methadone maintenance OBJECTIVES To revise 2010 guidance on grading the strength of evidence ( SOE ) of the effectiveness of drugs , devices , and other preventive and therapeutic interventions in systematic review s produced by the Evidence -based Practice Center ( EPC ) program , established by the US Agency for Healthcare Research and Quality ( AHRQ ) . STUDY DESIGN AND SETTING A cross-EPC working group review ed authoritative systems for grading SOE [ primarily the approach from the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) working group ] and conducted extensive discussion s with GRADE and other experts . RESULTS Up date d guidance continues to be conceptually similar to GRADE . Review ers are to evaluate SOE separately for each major treatment comparison for each major outcome . We added reporting bias as a required domain and retained study limitations ( risk of bias ) , consistency , directness , and precision ( and three optional domains ) . Additional guidance covers scoring consistency , precision , and reporting bias , grading bodies of evidence with r and omized controlled trials and observational studies , evaluating single study bodies of evidence , using studies with high risk of bias , and presenting findings with greater clarity and transparency . SOE is grade d high , moderate , low , or insufficient , reflecting review ers ' confidence in the findings for a specific treatment comparison and outcome . CONCLUSION No single approach for grading SOE suits all review s , but a more consistent and transparent approach to reporting summary information will make review s more useful to the broad range of audiences that AHRQ 's work aims to reach . EPC working groups will consider ongoing challenges and modify guidance as needed , on issues such as combining trials and observational studies in bodies of evidence , weighting domains , and combining qualitative and quantitative syntheses Background : Many physicians are still skeptic to treat opioid dependants , with or without maintenance treatment , for hepatitis C ( HCV ) because of concerns about psychiatric comorbidity , stability and adherence . In Norway , there are about 3,500 patients participating in the restrictive medication-assisted rehabilitation ( LAR ) programs in which all patients are given methadone or buprenorphine maintenance therapy . This study was undertaken to determine whether HCV combination therapy with pegylated interferon α-2a plus ribavirin is feasible , efficient and safe in this patient group . Method : Seventeen patients with HCV genotype 3a were treated for 24 weeks . To optimize compliance , the treatment was given from a department of infectious diseases in cooperation with an LAR center . All injections were given in the LAR center and the patients were given psychosocial support . Results : The compliance was 100 % . All responded to the therapy and 16 ( 94 % ) were sustained responders . Discussion / Conclusion : This study indicates that compliance and treatment outcome of opioid dependants on methadone or buprenorphine maintenance after 24 weeks of HCV treatment corresponds to that for non-dependants if extra support is given . The treatment should be undertaken in collaboration with specialists in addiction medicine , hepatology and infectious diseases Injection drug use accounts for the majority of incident and prevalent cases of hepatitis C virus ( HCV ) infection . However , very few injection drug users ( IDUs ) have received treatment for this condition given issues of medical or psychiatric co-morbidity , ongoing substance abuse and a widely held belief that such individuals will not be able to adhere to the requirements of therapy , including regular medical follow-up . With this in mind , we sought to evaluate HCV treatment uptake and outcomes among current and former IDUs attending a weekly peer support group and receiving directly observed HCV therapy . Utilizing the existing infrastructure for the management of addictive disease , we have developed a model of " one-stop shopping " whereby the treatment of addiction , HCV and other medical conditions are fully integrated , with the collaboration of nurses , counsellors , addiction specialists , infectious disease specialists , primary care physicians and research ers . Subjects interested in receiving treatment for HCV infection were referred to a weekly peer-support group and evaluated for treatment . Patients received therapy with pegylated interferon-alpha2a or -alpha2b , both in combination with ribavirin . All injections were directly observed . Overall , we observed a high uptake of HCV treatment among attendees , with 51 percent either receiving or about to receive therapy . To date , 18 patients have initiated treatment for HCV infection and 12 have completed therapy . Overall , 8/12 ( 67 percent ) subjects achieved an end of treatment response ( genotype 1 , 67 percent ; genotypes 2/3 , 67 percent ) , despite ongoing drug use in 75 percent of patients during treatment . These data demonstrate that with the appropriate programs in place , a high uptake of HCV treatment can be achieved among IDUs referred to a peer-support group . Moreover , the treatment of HCV in current and former IDUs within a multidisciplinary DOT program can be successfully undertaken , result ing in ETRs similar to those reported in r and omized controlled trials We assessed the feasibility of field-based directly observed therapy ( DOT ) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai , India . Fifty participants were r and omized 1:1 to sofosbuvir+peginterferon alfa 2a+ribavirin ( SOF+PR ) for 12 weeks ( Arm 1 ) vs sofosbuvir+ribavirin ( SOF+R ) for 24 weeks ( Arm 2 ) . SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic . HCV RNA testing was performed to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion ( SVR12 ) . No baseline genotyping or on-treatment viral loads were performed . Median age was 46 years . All were male and 20 % had significant fibrosis/cirrhosis . All self-reported history of injection drug use , 18 % recent noninjection drug use and 38 % alcohol dependence . Six discontinued treatment ( 88 % completed treatment in each arm ) . Of 22 who completed SOF+PR , all achieved SVR12 ( 22/25=88 % ) ; 15 of 22 who completed SOF+R achieved SVR12 ( 15/25=60 % ; P=.05 ) . Among those completing SOF+R , SVR12 was significantly less common in participants reporting ongoing substance use ( 36 % vs 100 % ) and missed doses . Active substance use and missed doses did not impact SVR with SOF+PR . Field-based DOT of HCV therapy without real-time HCV RNA monitoring was feasible ; however , achieving 100 % adherence was challenging . SOF+PR appeared superior to SOF+R in achieving SVR12 , even when doses were missed with no discontinuations due to side effects . Further exploration of short duration treatment with peginterferon plus direct-acting antivirals is warranted |
2,181 | 25,664,612 | Implant location , type of restoration , and implant number do have an influence on the estimated implant loss rate . | OBJECTIVES The aim of this systematic review was to analyze post-loading implant loss for implant-supported prostheses in edentulous jaws , regarding a potential impact of implant location ( maxilla vs. m and ible ) , implant number per patient , type of prosthesis ( removable vs. fixed ) , and type of attachment system ( screw-retained , ball vs. bar vs. telescopic crown ) . | OBJECTIVE The aim of the present prospect i ve clinical study was to compare patient-reported outcomes for maxillary conventional dentures and maxillary implant-supported dentures . MATERIAL AND METHODS Twenty-one patients ( 6 women and 15 men ) being edentulous in the maxilla and encountering problems with their existing dentures were included . Twelve patients ( 4 women and 8 men ) received a new set of conventional dentures , due to insufficient dentures . In nine patients ( 2 women and 7 men ) , the existing dentures were adjusted by means of relining or rebasing . All patients received implant-supported dentures on two retentive anchors . In total , 42 implants were inserted in the anterior maxilla . The participants rated their satisfaction on their existing conventional dentures , 2 months after insertion of new conventional dentures and 2 months after insertion of implant-supported dentures . Thereby , patients responded to question naires capturing the oral health impact profile ( OHIP ) using visual analog scales . Seven domains ( functional limitation , physical pain , psychological discomfort , physical , psychological and social disability and h and icap ) were assessed . Higher scores implied poorer patient satisfaction . In addition , the question naire involved the evaluation of cleaning ability , general satisfaction , speech , comfort , esthetics , stability , and chewing ability . Higher scores implied higher patient satisfaction . RESULTS Patient satisfaction significantly increased for implant-supported dentures compared with old dentures in all seven OHIP subgroups , as well as for cleaning ability , general satisfaction , ability to speak , comfort , esthetics , and stability ( P < 0.05 ) . The comparison of new conventional dentures and implant-supported dentures revealed a statistically significantly increased satisfaction for functional limitation ( difference of 33.2 mm ) , psychological discomfort ( difference of 36.7 mm ) , physical disability ( difference of 36.3 mm ) , and social disability ( difference of 23.5 mm ) , ( P < 0.05 ) . Additionally , general satisfaction , chewing ability , speech , and stability significantly improved in implant-supported dentures ( P < 0.05 ) . CONCLUSIONS Within the limits of this study , maxillary dentures retained by two implants provided some significant short-term improvements over conventional dentures in oral- and health-related quality of life PURPOSE The aim of the study was to compare the differences in the long-term clinical and radiologic effects for three different treatment strategies with implant-supported overdentures in the edentulous m and ible , with a special emphasis on smoking . MATERIAL S AND METHODS In a r and omized- controlled clinical trial , 110 edentulous patients participated . Thirty-six patients were treated with an overdenture supported by two implants with ball attachments ( 2IBA ) , 37 patients with an overdenture supported by two implants with a bar ( 2ISB ) and 37 patients with an overdenture supported by four implants with a triple bar ( 4ITB ) . After a mean evaluation period of 8.3 years , the clinical and radiographic parameters were evaluated . RESULTS Ninety-four out of the original 110 patients ( = 85 % ) were evaluated . In the 2IBA group , the plaque index was significantly lower ( vs. 2ISB , P=0.013 ; vs. 4ITB , P=0.001 ) than in the other groups , but there was no correlation with the other peri-implant parameters . In the 4ITB group , the marginal bone loss was significantly higher than that in the two implant groups . The maximal probing depth was correlated with peri-implant bone loss ( P=0.011 ) . Smoking almost doubled marginal bone loss irrespective of the treatment strategy chosen . CONCLUSIONS Patients with two implants show less marginal bone loss than those with four implants . Smoking is a risk factor for the survival of dental implants in the long run PURPOSE The present study evaluated implant survival/success rate , peri-implant parameters and prosthodontic maintenance efforts for four implant-supported m and ibular overdentures ( IOD ) rigidly retained on either milled bar or double crowns ( telescopic ) attachments . MATERIAL AND METHODS In a r and omized prospect i ve trial , 51 patients with edentulism received four m and ibular interforaminal implants and complete maxillary dentures . For IOD , rigid denture stabilization was chosen r and omly selecting 26 patients for milled bars ( group I ) and 25 patients for double ( telescopic ) crowns ( group II ) . During a 3-year follow-up period , implant survival/success , peri-implant parameters ( marginal bone resorption , pocket depth , plaque- , bleeding- , gingival index [ BI and GI ] , calculus ) and prosthodontic maintenance efforts were evaluated and compared between both retention modalities used . RESULTS Forty-five patients ( 23 group I , 22 group II ) were available for a 3-year follow-up ( dropout rate : 11.8 % ) presenting a high implant survival/success rate ( 100 % ) . Peri-implant marginal bone resorption , pocket depth as well as BI and GI did not differ for both rigid retention modalities . However , annually higher values for plaque- ( NS ) and calculus index ( P<0.035 ) were noticed for the bar ( group I ) than for the telescopic crown ( group II ) attachments . Prevalence of prosthodontic maintenance did not differ between both retention modalities ( group I : 0.41/maintenance efforts/year/ patients vs. group II ; 0.45 maintenance/efforts/year/ patients ) . However , prosthodontic adaption for h and ling mechanism showed benefits for the bar retention . CONCLUSION Rigid anchoring of IOD retained either by bar or telescopic attachments showed high implant success rates and minor prosthodontic maintenance efforts regardless of retention modalities used . Stable denture retention presented healthy peri-implant structure for implants in bar and telescopic anchoring systems . Drawbacks such as higher plaque/calculus for bar retention and less favorable h and ling properties ( output ) for telescopic crown attachment leave the decision on the selection at the discretion of the clinician Treatment of the atrophic edentulous maxilla is challenging especially when bone graft procedures are necessary . In this study an onlay bone graft , a saddle or veneer , with or without maxillary sinus floor inlay graft , harvested from the anterior iliac crest , in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae . The aim was to investigate treatment outcome , and the impact of gender and smoking , in 44 patients in a prospect i ve , long-term , follow-up study concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant . Mean follow-up time was 11 years . Of 334 inserted Brånemark implants , with machined surface , 27 failed . Estimated implant survival rate was 90 % . Marginal bone loss was 1.8 mm 1 year after implant surgery ; 2.3 mm after 5 years ; and 2.4 mm after 10 years . There was a significant difference between genders in implant survival . Marginal bone loss differed significantly between smokers and non-smokers up to the 5-year examination and between genders after the 4-year examination . The onlay bone graft , with or without a maxillary inlay graft , results in high implant survival rate , good oral function and stabilised marginal bone . All patients are still wearing their original fixed bridges BACKGROUND Long-term follow-up studies ( i.e. , over 5 years ) , focusing on prosthetic outcomes and maintenance of implant-supported reconstructions in the edentulous maxilla , are scarce in the literature . PURPOSE The purpose of this study was to evaluate and report 10-year data on outcomes and maintenance of screw-retained implant-supported full-arch casted titanium-resin prostheses in the edentulous maxilla . MATERIAL S AND METHODS In the r and omized control trial cohort of 24 patients , the outcome and maintenance of 23 bridges were registered . RESULTS One patient dropped out of the study prior to the 10-year control . Of the 23 remaining patients , 21 still had their original frameworks ; one framework fractured after 8 years and one was remade after 7 years to create better support for the acrylic . The remaining 23 prostheses showed criteria of success , survival , and failure in 9 , 82 , and 9 % , respectively . Tightening of two assembly screws was necessary in one patient . No detrimental effects were seen because of long cantilever extensions or opposing dentition . A total of 4.7 resin-related complications per prosthesis were observed ; tooth fracture was the most common prosthetic complication . There was an indication of greater prevention in the number of resin-related complications with the use of lingual gold onlay compared with a resilient mouth guard , 0.71 and 1.67 , respectively per bridge . The bridges were removed and reinserted 0.83 times per patient . No abutment or abutment screw fractures were registered . CONCLUSION Fracture or wear of the reconstruction material s were considered predictable risks when using resin-based suprastructure material s. Status of opposing dentition and length of cantilevers did not confer additional risk . The use of a lingual gold onlay indicated prevention of resin-related complications . Future research should focus on the suprastructure material s to predict better overall treatment results of implant-supported full-arch bridges in the edentulous maxilla STATEMENT OF PROBLEM There is a widespread belief that maxillary overdenture prostheses are associated with a higher frequency of complications and require more maintenance than fixed implant prostheses . PURPOSE This prospect i ve clinical study compared the treatment outcomes of fixed and removable implant-supported restorations in the edentulous maxilla with the main emphasis on the clinician 's point of view . MATERIAL AND METHODS Ten patients were treated with fixed screw-retained implant prostheses ( group 1 ) , and 10 patients were treated with removable implant-supported overdentures ( group 2 ) in the edentulous maxilla . Recall was scheduled at 6-month intervals to investigate the prosthodontic treatment outcomes , including implant survival , prosthesis time until retreatment , and maintenance issues . Clinical parameters gingival index ( GI ) , plaque index ( PI ) , the clinical attachment level , and radiographic marginal bone levels measured , along with any biologic and mechanical complications were recorded . RESULTS Patients were followed over a mean period of 39 months ( SD=7 ; group 1 ) and 27 months ( SD=10 ; group 2 ) after implant placement . Cumulative implant survival was 97.6 % for group 1 and 94.4 % for group 2 after an 18-month observation period . The mean time until retreatment after prostheses insertion was 23.4 months for group 1 and 19.8 months for group 2 ( n.s . ) . In both groups , the increase over time in the radiographically investigated bone level was found to be significant . The indices given for the mucosal health and oral hygiene status ( GI and PI ) were highly correlated in both groups at each recall appointment , but no significant differences were found between groups 1 and 2 . CONCLUSION In groups 1 and 2 , comparable prosthodontic treatment outcomes were achieved . The majority of mechanical complications could be managed chairside during recall visits and did not require additional appointments , so that the time and costs involved in providing maintenance were kept down BACKGROUND Dental implants with moderately rough surfaces are commonly used in the treatment of edentulous patients . However , long-term data on survival rates and marginal bone conditions are lacking . PURPOSE This prospect i ve study evaluated the cumulative survival rate of the TiOblast implant ( Astra Tech AB , Mölndal , Sweden ) after 10 years of prosthetic loading . MATERIAL S AND METHODS A total of 199 TiOblast implants were placed in 36 consecutive edentulous patients ( 23 males and 13 females ) . All patients were treated at one clinic and by the same team . The patients were edentulous in either the maxilla ( n = 16 ) or the m and ible ( n = 20 ) . The average age of the patients at the start of the trial was 64 years ( range , 59 - 82 years ) . Of the 199 implants inserted 108 were in the m and ible and 91 were in the maxilla . Clinical evaluations were undertaken after completion of the prosthetic superstructure ( baseline ) and after 6 months , 1 year , 3 years , 5 years , 7 years , and 10 years . Mean marginal bone level was evaluated for the first 100 placed implants for up to 7 years . RESULTS Six implants failed during the study ( 3 in the m and ible and 3 in the maxilla ) . All failures occurred within the first year , giving a cumulative survival rate of 96.9 % ( 96.6 % in the maxilla and 97.2 % in the m and ible ) after 10 years of follow-up . The survival rate for the superstructures was 100 % . The mean marginal bone level in the measured sample was 0.2 mm ( st and ard deviation [ SD ] , 0.31 ) below the reference point at baseline , 0.28 mm ( SD , 0.20 ) and 1.27 mm ( SD , 1.15 ) below the same point 7 years later ( mean , 0.15 mm per year ) . CONCLUSION This study showed that titanium dioxide-blasted implants offer predictable long-term results as supports for fixed prostheses in both the maxilla and m and ible PURPOSE The present study evaluated implant and peri-implant outcomes as well as prosthodontic maintenance efforts for implant/bar-supported m and ibular prostheses with different prosthesis anchorage systems . MATERIAL S AND METHODS Seventy-six patients who received two or four interforaminal implants were assigned to one of three different bar design s and subsequently to different prosthesis supporting systems . Forty-nine patients received implants and a mucosa-supported implant-retained overdenture ( OD ) with an ovoid bar ( two implants ; design 1 ) or multiple ovoid bars ( four implants ; design 2 ) . Twenty-seven patients received four implants and a rigid implant-supported prosthesis ( ISP ) with a milled bar ( design 3 ) . Implant survival , peri-implant parameters ( marginal bone resorption , pocket depth , and plaque , bleeding , gingival , and calculus indices ) , and postinsertion prosthodontic maintenance were followed over a 5-year period and compared among the different retention modalities . At the most recent follow-up examination , subjective patient satisfaction was additionally evaluated using a simplified scoring system ( ranging from 1 = not satisfactory to 5 = excellent ) . RESULTS Implant survival rates ( 100 % ) and all peri-implant parameters evaluated showed no differences among the three design s used for implant prosthesis anchorage . Prosthodontic maintenance did not differ between the different ODs ( OD design 1 : average of 1.04 maintenance visits/year/patient ; OD design 2 : 1.2 maintenance visits/year/patient ) , but it was significantly lower for the dentures that were rigidly stabilized with milled bars ( ISP : 0.37 maintenance visits/year/patient ) . A high subjective satisfaction rate ( range : 4.5 to 5.0 ) was registered at the final examination , without any differences among the design s used . CONCLUSIONS Rigid anchorage with milled bars on four-implant prostheses combined with a metal-reinforced framework showed a lower extent of prosthodontic maintenance issues than round bars on two- or four-implant overdentures with resilient denture stabilization . Nevertheless , implants and peri-implant structures were not negatively affected by either resilient or rigid anchorage mechanisms INTRODUCTION Immediate functional loading of dental implants for full-arch restoration is a patient-friendly approach , shown to be feasible with a good long-term prognosis in a completely edentulous m and ible . For the complete restoration of the maxilla , acceptable long-term clinical follow-up is lacking or based on case reports rather than on prospect i ve studies . OBJECTIVES This prospect i ve mono-centre study reports the 3-year outcome of immediately functionally loaded Astra Tech Dental implants in completely edentulous maxillae based on clinical survival and success based on radiographical assessment of bone level . MATERIAL AND METHODS One hundred and ninety-five Astra Tech TiOblast surface fixtures were installed in 25 consecutively treated patients ( age range : 42 - 76 years ) , of whom eight were smokers , 12 had a confirmed history of periodontitis and six had poor bone quality normally deemed for delayed loading . Fixtures and abutments were inserted in a one-stage procedure and functionally loaded within 24 h with a 10-unit provisional glass-fibre or metal-reinforced screw-retained restoration . After 6 months , each implant was checked for stability using a manual torque of 20 N cm and the provisional restoration was replaced by a 10 - 12-unit screw-retained metal-ceramic or metal-resin cantilever bridge . Bone level was assessed radiographically from the day of surgery up to 3 years and used to calculate mean bone loss at the patient level and individual implant success . RESULTS No failures occurred in implants or prostheses , the total survival rate being 100 % . Mean marginal bone loss was 0.58 mm ( SD 0.58 ) ; 0.6 mm ( SD 0.53 ) ; 0.63 ( SD 0.61 ) ; and 0.72 ( SD 0.63 ) after 6 and 12 months , and 2 and 3 years , respectively , yielding a 100 % success at the patient level . Wilcoxon 's signed ranks test showed only statistically significant bone loss between baseline and 6 months and a steady-state condition during all other intervals . At the individual fixture level , 82 % lost < 1 mm marginal bone between baseline and 1 year . After 3 years , 86 % have < 1.5 mm total bone loss and can be considered a success . The fixtures expressing more bone loss were all inserted in smokers . CONCLUSION Immediate loading of a full-arch maxillary bridgework on 7 - 9 Astra Tech TiOblast implants is a predictable treatment option with 100 % fixture survival and stable bone-to-implant contact up to 3 years . The steady state in bone remodelling is indicative of a good long-term prognosis in non-smokers but smokers seem to be more prone to bone loss BACKGROUND There have been very few long-term controlled studies ( i.e. , over 5 years duration ) focusing on marginal conditions for implants with a s and blasted , large grit , and acid-etched ( SLA ) surface . PURPOSE To evaluate and report 10-year data on outcomes of implants with an SLA surface placed in the edentulous maxilla . MATERIAL S AND METHODS In a r and omized controlled trial ( RCT ) cohort of 24 patients , the outcomes of implants with an SLA surface were registered . The RCT cohort has previously been reported after 1 year , 3 years , and 5 years of loading . RESULTS One patient dropped out of the study prior to the 10-year control . Of the 23 remaining patients , the implant survival rate was 95.1 % . If implants of unknown status were also considered lost , that is , one drop-out patient with three implants for whom no information could be obtained , the implant survival rate was 93 % . The mean marginal bone loss from baseline ( 139 implants ) to 10 years ( 102 implants ) was 1.07 mm ( st and ard deviation 0.98 ) . One implant out of 102 available for radiographic examination according to the original protocol showed a bone loss exceeding 4 mm . Of the 84 implants available for clinical examination , none showed a Plaque Index or sulcus bleeding index of 3 . The mean implant stability quotient was significantly higher for mesial-distal versus buccal-palatal measurements . CONCLUSION The implant survival was 95.1 % . The mean value of bone loss after 10 years was 1.07 mm . Peri-implantitis were noted at the 5-year follow-up for one patient with a previous history of periodontitis ; this patient did not attend the 10-year follow-up . This study shows that s and blasted and acid-etched implants offers predictable long-term results as support for full-arch maxillary prostheses PURPOSE The aim of this 5-year prospect i ve evaluation was to assess the bone and peri-implant mucosa responses at unsplinted , microthread implants supporting m and ibular overdentures and to determine patient responses to therapy . MATERIAL S AND METHODS Two implants were placed by a 1-stage procedure in the parasymphyseal m and ibles of 59 subjects . Implant placement was followed by immediate insertion of overdentures without connection to abutments . After 3 months , connection using Dalla Bona attachments was made and peri-implant mucosa , peri-implant bone , and patient perceptions of treatment were evaluated . RESULTS The implant success rate was 95.9 % from 6 to 60 months . The changes in marginal bone levels were positive ( bone gain ) but did not reach statistical significance at 12 , 36 , or 60 months ( + 0.13 + /- 0.59 mm , + 0.23 + /- 0.66 mm , and + 0.09 + /- 0.79 , respectively ) . Treatment was viewed as effective ; patients rating satisfaction with their teeth increased from a preoperative level of 12.1 % to 94.6 % at overdenture abutment connection and remained high ( 81.6 % ) after 5 years . CONCLUSIONS Expedited m and ibular overdenture therapy utilizing unsplinted , microthreaded m and ibular parasymphyseal implants was associated with high implant survival , preservation of crestal bone , and high patient satisfaction . Complications were minor and related to prosthodontic features of therapy PURPOSE The aim of this prospect i ve study was to evaluate the concept of intraoral welding as a suitable technique for the fabrication of a restoration for the edentulous atrophic maxilla on the day of placement of axial and tilted implants . MATERIAL S AND METHODS Thirty patients received three axial and four tilted implants in the edentulous maxilla . Immediately after implant placement , definitive abutments were connected to the implants and then a titanium bar was welded to them using an intraoral welding unit . This framework was used as a support for the definitive restoration , which was attached on the day of implant placement . Mean marginal bone loss and radiographically detectable alteration of the welded framework were assessed using periapical radiographs immediately after surgery and at 6 , 12 , 24 , and 36 months after placement . RESULTS Sixteen men and 14 women with an average age of 58.1 years ( SD 13.6 ) were consecutively treated with 210 immediately loaded implants . No fractures or radiographically detectable alterations of the welded frameworks were evident . A 100 % prosthetic success rate was seen at 36 months . Three ( 1.4 % ) implants had serious biologic complications , result ing in success rates of 97.8 % for axial implants and 99.2 % for tilted implants . The accumulated mean marginal bone loss was 0.92 mm ( SD 0.75 ; n = 90 ) for axial implants and 1.03 mm ( SD 0.69 ; n = 120 ) for tilted implants . The average pocket probing depths were 1.87 mm ( SD 0.98 ; n = 90 ) for the axial implants and 1.95 mm ( SD 0.81 ; n = 120 ) for the tilted implants . CONCLUSIONS It is possible on the day of implant placement surgery to successfully rehabilitate the edentulous atrophic maxilla with a fixed , definitive restoration supported by an intraorally welded titanium framework attached to axial and tilted implants PURPOSE The aim of this study was to prospect ively evaluate the clinical and radiographic outcomes of immediate full-arch fixed maxillary prosthesis supported by two axial and four tilted implants after 3 years of loading . MATERIAL S AND METHODS Thirty-two patients with atrophic maxilla were consecutively enrolled and treated . Each patient received a fixed full-arch maxillary rehabilitation supported by four tilted implants that engaged the posterior and the anterior sinus walls and two axial anterior implants . A total of 192 implants ( 30 Brånemark System MK IV and 162 NobelSpeedy Groovy , Nobel Biocare AB , Göteborg , Sweden ) were inserted and immediately loaded . The definitive restorations were placed 6 months later , and follow-up visits were scheduled every 6 months . During follow-ups , marginal bone loss ( MBL ) , plaque and bleeding scores , and patient 's satisfaction were recorded . RESULTS All patients reached at least 3-year follow-up examination ( range 36 - 78 , average 55.53 months ) . Two tilted implants failed before delivering the definitive restoration , result ing in a cumulative survival rate of 98.96 % . All final prostheses were stable and functional , result ing in a cumulative survival and success rate of 100 % . At the 3-year follow-up there was no significant difference in MBL between axial ( 1.55 ± 0.31 mm ) and tilted implants ( 1.46 ± 0.19 mm ) ( p = .05 ) . Plaque and bleeding scores decreased over time , while patient 's satisfaction in both aesthetics and function increased . CONCLUSIONS Implants placement with this configuration could be considered a predictable and cost- and time-effective alternative approach for the immediate restoration of the edentulous maxilla , avoiding bone grafting procedures , even with a medium-term follow-up PURPOSE A longitudinal 5-year clinical investigation was carried out to compare screw-retained frameworks constructed from two alloys with different mechanical properties , either gold or silver-palladium , supported in the m and ible by the Astra Tech implant system . MATERIAL S AND METHODS Twenty-six edentulous patients with m and ibular implants were divided into two groups : group A was provided with Chicago IV gold alloy superstructures , and group B was provided with Palliag M silver-palladium alloy superstructures . The surgical procedures for placing the m and ibular bone implants and the prosthodontic and laboratory techniques for constructing the prostheses were carried out according to st and ard , well-documented practice s. All patients wore conventional maxillary complete dentures . The integrity of prostheses and health of supporting tissues were compared over a 5-year period . RESULTS Both material s had similar accuracy of fit and resistance to functional stress , although silver-palladium was technique sensitive and necessitated meticulous laboratory practice to achieve accuracy of casting . Clinical performance of both prostheses was similar , and radiographic assessment showed no statistically significant differences in periimplant bone changes . CONCLUSION There were no differences in clinical performance and radiographic changes between the two material s. Therefore , silver-palladium alloy may be considered a suitable low-cost substitute for gold alloy for fixed implant-supported prostheses STATEMENT OF PROBLEM The results of the implant overdenture treatment in the maxilla remains inferior to those in the m and ible . Different reasons have been alluded to , such as bone quality and quantity , number of implants , as well as the prosthesis design . PURPOSE To investigate the latter , a new design for the rehabilitation of the resorbed maxillae was set up . MATERIAL AND METHODS Thirteen patients were selected and provided with four endosseous maxillary implants , splinted with a rigid-cast bar . RESULTS After a mean loading time of 3 years , six implants were lost ; three at abutment and another three shortly after abutment connection , result ing in a cumulative success rate of 88.6 % at year 4 . A mean marginal bone loss of 0.3 mm was observed within the first year . After the first year , the marginal bone level , the attachment level , and the Periotest scores hardly changed . The main prosthetic complication was the frequent need to renew or to activate the attachments . A strong improvement in patient satisfaction was observed when compared with the old conventional denture . CONCLUSIONS Within the limits of this study , the outcome confirmed that , on a medium-term base , implant-retained hinging overdentures on four implants were promising AIM The purpose of this study was to evaluate the survival and success of early-loaded implants placed in the intraforaminal area of the edentulous m and ible , and the survival of the implant-supported fixed dental prostheses ( FDP ) . MATERIAL AND METHODS Thirty-seven patients ( 18.9 % male , mean age 64.5 years ) with edentulous lower jaws were treated with implant-supported FDPs in the m and ible . One hundred and eighty-five screw-type implants were placed in the intraforaminal area of the symphysis ( five implants per patient ) . Immediately after implant placement , a framework was fabricated and the FDP was manufactured on the framework . Within 2 weeks , the implants were rigidly connected and loaded with the implant-retained FDP . RESULTS During the 1 - 8-year observation period ( mean 4.5 years ) , a total of 32 implant-retained complications occurred . Nineteen implants were lost in 10 patients , result ing in a cumulative survival of 89.7 % . Nine implants in five patients did not osseointegrate . Although these implants were not removed , because stability within the connective tissue was acceptable and inflammation was absent , they were recorded as unsuccessful . Consequently , the cumulative success declined to 84.9 % . Four implants in three patients had clinical signs of periimplantitis ( 2.2 % of all implants ) . Denture-related complications included one complete failure , when one FDP had to be removed after the last of five implants had been replaced . Furthermore , 10 fractures of the framework occurred in six patients , three FDPs had to be adapted or modified , and the facing of the FDP had to be repaired 16 times in 11 patients . CONCLUSION Although one-stage early-loaded implants functioned well for most patients with edentulous m and ibles , immediate loading is associated with a larger number of implant-related complications than in other studies investigating delayed loading . Because of the substantial prosthetic complications and aftercare , this procedure can not be generally recommended INTRODUCTION Edentulism causes progressive bone resorption of the maxillae , which can lead to altered maxillo-m and ibular relationships . The aim of the study was to evaluate the applicability of guided bone regeneration ( GBR ) to Le Fort I osteotomies with interpositional bone grafts for treatment of patients with severe maxillary atrophy . MATERIAL S AND METHODS Twenty consecutive patients characterized by severely atrophic maxillae were treated from January 2003 to January 2006 in order to resolve maxillary edentulism . All patients underwent pre-prosthetic surgery , including a Le Fort I osteotomy associated with autologous interpositional bone grafts to move the alveolar arch forward and to resolve the maxillary atrophy . Barrier membranes were also used to cover the bone grafts and the osteotomy line , favoring the healing process according to GBR principles . Maxilla advancement and alveolar crest augmentation were measured to assess the degree of reconstruction . A total of 154 implants were inserted in reconstructed maxillae 4 months after surgery and were restored with fixed full-arch dentures after another 4 months . Surgical and prosthetic complications were recorded and previously established implant success criteria were used to assess the success of this treatment protocol . RESULTS The outcome of pre-prosthetic surgery and implant-supported rehabilitation was prospect ively evaluated every year . All Le Fort I osteotomies were successfully carried out , with a mean maxilla advancement of 4.2 cm ( range : 3.1 - 5 cm ) , which appeared to be stable during the follow-up . After a mean follow-up of 66.4 ± 18.4 months , only four implants failed according to the success criteria , yielding a cumulative success rate of 95.8 % . DISCUSSION AND CONCLUSIONS Le Fort I osteotomies with the use of barrier membranes to cover the interpositional bone grafts can be a predictable treatment for edentulous patients with severely resorbed maxillae . The study data suggest that this approach makes it possible to compensate for both sagittal and vertical discrepancies due to maxilla atrophy , with a minimum resorption of advanced maxillae and grafted bone . A GBR-based protocol seems to lead to high implant success rates , although further r and omized controlled studies are needed to demonstrate the usefulness and advantageousness of GBR PURPOSE The aim of this prospect i ve cohort study was to determine the 5-year implant survival and success rates associated with early loading ( 6 weeks after nonsubmerged placement ) of s and blasted and acid-etched ( SLA ) Straumann implants in the edentulous m and ible . A secondary objective was to determine the peri-implant tissue response and measure alterations in peri-implant crestal bone levels . MATERIAL S AND METHODS SLA implants were placed and primarily loaded 6 weeks later with 35 Ncm during abutment placement . The peri-implant bone and mucosal conditions of the participants were monitored radiographically and clinical ly over a 5-year period . RESULTS Fourteen patients received 60 implants . Thirteen patients and 54 implants were examined at the 5-year appointment . Two of 60 implants failed during the healing period , and four implants were lost during follow-up and considered as dropouts . The remaining implants showed favorable clinical and radiographic findings and were considered successfully integrated at the 5-year examination . The mean loss of crestal bone height after 5 years was 0.77 mm ( SEM 0.09 ) . This result ed in a 5-year cumulative success rate of 96.7 % . CONCLUSION In this prospect i ve study , the early loading of Straumann implants with the SLA surface in the edentulous m and ible after a healing time of 6 weeks provided successful osseointegration with high predictability . Successful integration was maintained for 5 years OBJECTIVES This prospect i ve multicentre study provides clinical experience up to 3 years to support a simplified treatment for m and ibular edentulism within 1 week by using one-stage implant surgery and a screw-retained full-arch bridge . METHODS Two hundred and fifty ITI Monotype ® implants were installed in 62 patients out of 66 patients ; 60 patients got four implants each and two got five implants . After 1 week , a final bridge was in function . Radiographs were taken as baseline for vertical bone loss up to 3 years post-loading for the whole cluster and specific effects of gender , centre , age , bone class , implant length over time were compiled . Clinical ( mPI , SBI ) and subjective parameters such as general oral hygiene and patient satisfaction were recorded and repeated at specified intervals up to 3 years . RESULTS Four patients were excluded at surgery and are not involved in the follow-ups . At 1 year , 61 patients ( 244 implants ) were evaluable and all bridges were in function . After 3 years , 49 patients ( 194 implants ) came to control . Eight patients died during the follow-up period . Three patients lost one implant each . The cumulative implant survival rate was 98.55 % and the success rate for the prosthesis was 100 % . As calculated from measurable radiographs , the mean bone level at baseline was 1.63±0.78 and at 1 and 3 years 2.50±0.60 and 2.56±0.74 , respectively . Using the mixed model analysis and Friedman test , the time in situ , centre and bone class had significant effect on the bone resorption and to some small extent even , the implant length . Gender and age were unaffected . Oral hygiene and patient satisfaction of the treatment were improved . CONCLUSIONS The results indicate that one-part self-tapping s and blasted , large-grit , acid-etched ( SLA ) implants are suitable for loading within 1 week . In the whole period , the mean bone crestal resorption was < 1 mm , which is in agreement with other similar studies BACKGROUND Interest in the use of one-stage surgery and immediate loading of oral implants has lately been increasing . PURPOSE The aim of this study was to compare the 3-year results of one-stage surgery versus two-stage surgery , early loading versus loading after a 3-month healing period , and the use of one-piece implants versus the use of two-piece implants . MATERIAL S AND METHODS The study included 108 patients with edentulous m and ibles . Each patient was treated with four Brånemark System implants ( Nobel Biocare AB , Göteborg , Sweden ) and with full fixed prostheses . Patients were consecutively treated and were distributed in four groups : group A ( one-stage surgery ) , group B ( control group with two-stage surgery ) , group C ( one-piece implants ) , and group D ( early loading ) . In groups A and B Brånemark St and ard implants and st and ard abutments were used . In group C the conical one-piece Brånemark implant was used , and in group D the patients had Brånemark System Mk III implants together with multiunit abutments . All patients were observed for 3 years . RESULTS Of the 432 inserted implants , 24 were lost . Survival rates in the three experimental groups ranged from 93.2 to 93.3 % whereas the survival rate in group B ( the control group with two-stage surgery ) was 97.5 % . The differences between the groups were not statistically significant . The changes in marginal bone level were measured from fixture insertion to the final follow-up at 3 years . The bone loss in group D ( early loading ) was significantly less than in group B ( the control group ) whereas there were no differences in marginal bone change between the other groups . CONCLUSIONS Early loading seemed to give good results in the anterior part of the m and ible . The survival rate of the early-loaded implants did not significantly differ from that of implants inserted with the conventional two-stage procedure , but the mean marginal bone loss around the surviving implants was less with early loading PURPOSE The aim of this longitudinal study was to gain 5-year clinical documentation of the 1-stage surgical technique in connection with ITI solid-screw implants used in the edentulous m and ible . MATERIAL S AND METHODS One hundred patients with totally edentulous m and ibles were treated with bar-retained overdentures supported by a total of 340 consecutively placed ITI solid-screw implants . The patients were followed at annual intervals for at least 5 years to evaluate implant success , longitudinal reactions of the peri-implant hard and soft tissues , and incidences of biologic and mechanical complications . RESULTS During the trial period , a total of 4 implants failed , all prior to loading , and 51 implants were lost to follow-up , result ing in a cumulative survival rate of 98.8 % after 5 years of functional service . The success analysis included additional strictly defined events ( either " first occurrence of marginal bone loss > or = 4 mm " or " first occurrence of pocket depth > or = 4 mm " and " first occurrence of crevicular fluid flow rate > or = 2.5 mm ) and result ed in a cumulative 5-year success rate of 95.7 % . The median marginal bone loss experienced between implant placement and prosthetic treatment was 0.5 mm , followed by an annual bone level change of 0.1 mm for the functional period of 5 years . The increasing incidence of remarkable plaque deposits from 19 % to 50 % represented the difficulties of the patients in maintaining a high level of oral hygiene , particularly for the lingual surfaces . Sulcus Bleeding Index , probing depth , attachment level , and crevicular fluid flow rate were used to describe the health of the peri-implant soft tissues and remained almost within acceptable st and ards . DISCUSSION Survival and success rates of implants , amount of marginal bone loss , and periodontal indices of peri-implant soft tissues were consistent with those reported in the literature regarding implants with the submerged healing concept . CONCLUSION With a cumulative survival rate of 98.8 % , a cumulative success rate of 95.7 % , and a median marginal bone loss of 0.5 mm during the healing period , followed by an annual rate of 0.1 mm after loading , non-submerged ITI solid-screw implants confirm the good clinical outcome of implant-supported treatment concepts for the rehabilitation of totally edentulous patients in a medium-term perspective PURPOSE The aim of the present study was to evaluate the prosthodontic maintenance required for m and ibular overdentures supported by 4 implants and splinted with either a round bar and resilient overdenture anchorage or a milled bar with rigid anchorage over a 5-year period . MATERIAL S AND METHODS In a r and omized prospect i ve trial , 51 edentulous patients received 4 m and ibular interforaminal implants to support an overdenture and maxillary complete dentures . For the implant-supported overdentures ( IODs ) , bar architecture and denture stabilization were chosen r and omly ; 25 patients received round bars ( group 1 ) and resilient anchorage and 26 patients received milled bars ( group 2 ) and rigid anchorage . The prosthodontic maintenance required for the IODs and opposing dentures were evaluated during a 5-year follow-up period and compared between the 2 retention modalities used for IODs . RESULTS Forty-six patients ( 22 in group 1 , 24 in group 2 ) were available for a 5-year follow-up ( dropout rate : 9.8 % ) . Prosthodontic maintenance efforts were significantly greater ( P < .01 ) with the round bar design ( group 1 ) than with the overdentures stabilized with milled bars ( group 2 ) . In group 1 , prosthodontic maintenance efforts were more frequent in the early phase of use ( 1 to 2 years ) , as compared with an evenly distributed incidence over the 5-year period with the rigid milled bar system . Major prosthetic complications ( IOD remaking , bar fracture ) were only seen in cases without metal-reinforced frameworks ( group 1 ) . CONCLUSION When 4 interforaminal implants are used to anchor m and ibular overdentures , the design of the anchorage system will significantly affect prosthodontic maintenance efforts and complication rates . Rigid anchorage using milled bars and a metal-reinforced denture framework required less prosthodontic maintenance , ie , for clip activation/fracture , than resilient denture stabilization using multiple round bars without a rigid denture framework OBJECTIVES This prospect i ve mono-center study describes a clinical technique to provide dental implants with a temporary cross-arch cantilever bridge functionally loaded on the day of fixture insertion and discusses the 3-year follow-up of four to six machined surface Brånemark implants installed in the interforamina area . MATERIAL AND METHODS Ninety Brånemark implants were installed in 18 edentulous m and ibles . Five patients were heavy smokers and one had Down syndrome . The day of surgery , a 10 unit provisional glassfiber-reinforced cantilever bridge was installed . The final 12 unit bridge was in place after an average of 144 days ( range 10 - 332 ) . Bone-to-implant level was assessed radiologically from the day of surgery up to 3 years . RESULTS Two out of five fixtures were lost within 3 months in the Down syndrome patient but the provisional bridge continued to function on the three remaining implants until the patient was successfully reoperated . Another implant was lost after 11 months due to a non-detected fracture in the metal framework , result ing in overloading of the cantilever part . As no additional losses occurred during the follow-up time ( range 57 - 26 months ) , the total failure rate is 3/91 ( 3.3 % ) . Seventeen of the 18 patients are loading their implants more than 3 years and nine have moved beyond the 4-year period . Average bone remodelling as measured on the apical radiographs from 12 patients at 0 , 12 and 36 months revealed a statistically significant bone loss from the initial 0.1 mm [ st and ard deviation ( SD ) 0.2 ; range 0 - 0.7 ] toward 1.8 mm ( SD 0.2 ; range 1.6 - 2.2 ) during the first year of function . ( Wilcoxon 's signed rank test ; P<0.002 ) . After 3 years , no further significant bone loss occurred . CONCLUSION This 3-year study shows that machined surface Brånemark implants can be immediately loaded with cross-arch cantilever bridges with an average bone-remodelling pattern indicative of a steady state after 1 year of loading OBJECTIVES The aim of this prospect i ve case series was to evaluate the results of an immediate loading concept using four Xi VE S plus implants in the edentulous m and ible , after a period of up to 10 years of clinical function . MATERIAL AND METHODS Thirty patients were treated with four implants each placed interforaminally and provisionally restored within 1 week . Radiographic bone levels , condition of the peri-implant mucosa , implant survival and success were recorded annually from implant insertion ( baseline ) up to 10 years after final restoration . RESULTS A total of 120 Xi VE S plus implants were placed in the interforaminal region . A significant coronal bone loss of 1.80 mm ( SD ± 0.65 ) was recorded within the first 8 years of function ( P < 0.001 ) . Within the next years no further significant increase of bone resorption was observed . The mean values of the plaque , calculus , bleeding and mucosal indices and probing depth remained low throughout this period . All implants were inserted with an insertion torque of more than 32 N cm . Two losses ( 1.7 % ) occurred prior to permanent restoration ( 1 and 3 months post-insertion ) , result ing in a survival rate of 98.3 % over the entire observation period . Four implants were recorded as failures due to excessive bone resorption , result ing in an overall success rate of 95 % . CONCLUSIONS The results of this study indicate that in selected patients immediate restoration of dental implants in the edentulous m and ible will achieve a clinical ly predictable outcome In this prospect i ve study 47 edentulous patients were treated with m and ibular fixed prostheses supported by osseointegrated Brånemark implants and followed for 12 to 15 years . Three ( 1 % ) of the 273 inserted implants were lost , two before and one six years after placement of the fixed prosthesis . The cumulative success rate ( CSR ) of the implants was 98.9 % both after 10 and 15 years . None of the fixed prostheses was lost and at the last follow-up , all patients had stable fixed prostheses in function ( CSR 100 % ) . The marginal bone loss around the implants was small , on average 0.5 mm during the first post surgical year and thereafter about 0.05 mm annually . More bone was lost around the anterior implants than around the most posterior ones . Smoking and poor oral hygiene had significant influence on bone loss , while occlusal loading factors such as maximal bite force , tooth clenching and length of cantilevers were of minor importance . It is concluded that the long-term results of the m and ibular implant treatment were extremely successful , regarding both the fixed prostheses and implant stability . Bone resorption around the implants , albeit limited , was influenced by several factors , smoking and oral hygiene appeared to be most important Immediate loading of endosseous implants is becoming a widespread therapeutic procedure for the rehabilitation of patients with edentulous jaws . The purpose of this prospect i ve clinical trial was to evaluate the long-term success rate of endosseous implants placed in the edentulous lower jaw and loaded on either the same day of surgery or the next day . Nineteen patients were enrolled in the study . Eleven patients , accounting for 64 implants , received their provisional prosthesis the same day of implant placement , and 8 patients , accounting for 52 implants , were rehabilitated the day after surgery . All patients were rehabilitated by a hybrid prosthesis supported by 5 to 6 Osseotite implants . Two implants failed in the group of patients who had their implants loaded the same day ( 96.9 % success rate ) , whereas 1 implant failed in the other group ( 98.1 % success rate ) . The overall implant success rate was 97.4 % . All failures occurred within 2 months of function . No other complication was reported . The mean follow-up for this interim report was 37.8 + /- 16.5 months ( range 8 - 65 months ) . Crestal bone loss was similar to that reported for st and ard delayed loading protocol s. The results of this study suggest that the rehabilitation of the edentulous lower jaw by an immediate occlusally loaded implant-supported hybrid prosthesis is equally successful when loading is applied the same day or the day after implant placement . Immediate loading with 5 to 6 implant-supported prostheses represents a viable alternative treatment to classic delayed loading protocol PURPOSE The aim of this study was to ascertain whether simplifying m and ibular overdenture treatment by using single-stage surgery and immediate prosthetic loading of a single implant will achieve acceptable implant success rates , functional improvement , and increased patient satisfaction . As part of this study , the Mk III Branemark implant with an oxidized surface was compared to the classic machined Mk III Branemark implant . MATERIAL S AND METHODS Thirty-five patients ( mean age : 68 years ) with problematic m and ibular dentures were treated . The primary complaints among the patients referred to the clinic for treatment were poor retention of the m and ibular denture , instability , denture sores , and phonetic problems . Initially , patients were placed r and omly into the " machined surface " or " oxidized surface " groups . A single implant was placed in the m and ibular midline with high initial stability . A ball attachment was placed and the retentive cap incorporated into the existing denture . Review s took place at 3 , 12 , and 36 months posttreatment . Clinical assessment s , radiographs made with custom film holders , and stability measurements by both manual and resonance frequency analysis methods were recorded . All complications , failures , maintenance , and reasons for dropout were noted . Visual analog scale question naires were used to record patient satisfaction ( analysis of variance : P < .05 ) . RESULTS Three of eight machined-surface implants failed , representing an unacceptably high failure rate ( 37.5 % ) . The machined surface was therefore discontinued for this study . One machined and two oxidized-surface implants did not achieve sufficient primary stability to be immediately loaded , so they were treated with a two-stage delayed loading protocol . The 25 immediately loaded oxidized-surface implants were all classified as surviving at the 36-month recall . Patient satisfaction was very high with a significant increase in all comfort and functional parameters . CONCLUSIONS Within the limitations of this study and research design , it appears that over a 3-year observation period , the immediately loaded single implant-retained m and ibular overdenture , using an oxidized-surface implant and the existing prosthesis in a small group of prosthetically maladaptive patients , can provide a beneficial treatment outcome with a minimal financial outlay . Int J Prosthodont 2010;23:13 - 21 OBJECTIVES The aim of this preliminary prospect i ve study was to evaluate the clinical outcome , the oral health-related quality of life ( OHRQoL ) , and the subjective chewing ability of patients with m and ibular complete dentures retained by a single implant placed in the m and ible midline . METHODS Patients wearing complete dentures were treated with a single implant in the m and ible , followed by relining of the dentures and incorporation of ball attachments for implant retention . Implant outcome , prosthodontic maintenance , subjective chewing ability , and the oral health impact profile of the patients were assessed at baseline and at four weeks after connecting the denture and implant . RESULTS Eleven patients were enrolled in this investigation , and the mean observation period was 43.4 months ( minimum period : 35 , maximum period : 52 months ) . No implants were lost during observation period , but four dentures needed repair because of the fracture of the denture base in the midline area . A significant improvement was observed in the OHRQoL of the patients after the attachment of the m and ibular dentures with a single midline implant . Furthermore , the subjective chewing ability of the patients was significantly improved after implant connection . CONCLUSIONS Within the limitations of this preliminary prospect i ve clinical study , single implant-supported m and ibular overdentures were a successful treatment option for older edentulous patients who showed improvements in their OHRQoL and chewing ability PURPOSE Implant success , peri-implant conditions , and prosthodontic maintenance requirements were evaluated and compared for m and ibular overdentures supported by two implants and retained with ball or resilient telescopic crown attachments during a 5-year period . MATERIAL S AND METHODS Twenty-five patients with an edentulous m and ible each received two root-form dental implants in the m and ibular interforaminal ( canine ) region . The type of denture attachment was chosen r and omly ; 13 patients received ball attachments and 12 patients received resilient telescopic crowns . Implant success and peri-implant conditions ( bone resorption , pocket depth , Plaque Index , Gingival Index , Bleeding Index ) as well as prosthodontic maintenance and patient satisfaction were evaluated annually during a 5-year follow-up period and compared with respect to the two retention modalities used . RESULTS Implant success , peri-implant conditions , and subjective patient satisfaction scores did not differ between the two retention modalities used . However , during the 5-year observation period , significantly more postinsertion complications/ interventions for maintenance purpose s were registered in the ball group ( 87 interventions , 61.1 % ) than in the telescopic crown group ( 53 interventions , 37.9 % ; P < .01 ) . Differences in prosthodontic maintenance efforts were most significant in the second and third years ( P < .05 ) of the follow-up period but were similar at the end of the study for both anchorage systems . CONCLUSION Both ball attachments and resilient telescopic crowns on isolated implants in the atrophic m and ible are viable treatment options for implant-supported overdentures . No implant losses , good peri-implant conditions , and general patient satisfaction were noted . Although the frequency of technical complications was initially higher with ball attachments than with resilient telescopic crowns over a 5-year period , similar frequencies of maintenance efforts may be anticipated for both retention modalities This report of the 1st 2 prospect i ve studies using the Astra Tech Implant System and fixed detachable bridges for rehabilitation of m and ibular edentulism , presents clinical and radiographic data at the 5-year follow-up . The original material comprised 109 subjects , 56 of whom had been included in the original study , using the 1st generation Astra Tech Implant . Two subjects were excluded and the 3-year follow-up report was based on the remaining 54 subjects and 310 fixtures . After some minor changes to the fixture and the abutment , the 2nd generation Astra Tech Implant was used in 53 subjects and 308 fixtures . In all 16 subjects were lost to follow-up and the 5-year results are based on the remaining 91 subjects with 517 fixtures in function : 5 fixtures were lost due to mobility at abutment installation and during the 1st year , 2 fixtures were removed due to pain , and after 4 years in situ 1 fixture failed . As no clinical or radiographic differences were obvious in the annual registration s of the 2 studies the results have been combined . The fixed bridges were removed at 3 and 5 years to test each fixture and none was mobile . The cumulative fixture survival rate at 5 years was 98.7 % and the bridge survival rate was 100 % . Of the sites 82 % were plaque free , and 96.8 % showed no signs of inflammation . Over the 5-year period after bridge insertion , i.e. from baseline registration , there was only minor deterioration in marginal bone levels as measured on st and ardized intraoral radiographs : the mean differences in mm and st and ard deviations ( SD ) were -0.09 ( 0.27 ) in the 1st year , -0.20 ( 0.40 ) in the 3rd year , and -0.26 ( 0.53 ) in the 5th year . According to the stringent clinical and radiographic criteria by Albrektsson and co-workers , the successful treatment outcome and the survival rate in 91 subject over 5 years , indicates that the Astra Tech Dental Implant System with fixed detachable bridges is an appropriate method for rehabilitation of m and ibular edentulism PURPOSE The purpose of this controlled prospect i ve study was to compare the satisfaction of patients rehabilitated with an immediately loaded implant-supported prosthesis and patients rehabilitated with a conventional denture in the m and ible . MATERIAL S AND METHODS Selected m and ibular partially or totally edentulous patients were included in this prospect i ve study . Patients ' m and ibles were completely rehabilitated with immediately loaded implants supporting a screw-retained full-arch prosthesis ( test group ) or with a conventional denture ( control group ) . The Satisfaction Profile ( SAT-P ) , which investigates a number of psychologic aspects related to the function and esthetics of the stomatognathic apparatus , was administered to each patient 1 month before and 3 months after provisional prosthetic rehabilitation . The question naire comprised four different SAT-P items : quality of eating , eating behavior , mood , and self-confidence . A visual analog scale was used to elicit patient responses . SAT-P item scores were analyzed statistically by means of the Student t test and the chi-square test ( or the Mann-Whitney nonparametric test ) , with P < .05 considered significant . RESULTS Forty-one patients were consecutively treated with 205 immediately loaded implants supporting a screw-retained full-arch prosthesis ( test group ) ; 38 patients were consecutively treated with a conventional denture ( control group ) . Statistically significant differences were observed between the test and control groups for all four SAT-P items . The test group reported greater satisfaction for all items versus the control group . In both groups , the differences between pre- and postrehabilitation values were statistically significant . CONCLUSIONS Each patient was satisfied with their treatment outcomes , but patients who received an implant-supported prosthesis were more satisfied than the patients who received a conventional denture . The results suggest that a screw-retained full-arch prosthesis on immediately loaded implants is a predictable means of enhancing patient satisfaction A Le Fort I osteotomy and interpositional bone graft in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae . Surgery was performed in a two-stage procedure . The patients in this study had conditions with reversed intermaxillary relationships with or without increased vertical intermaxillary distance . The aim of the study was to investigate treatment outcome for patients in a prospect i ve , long-term , follow-up with a mean of 13 years ( range 11 - 16 years ) , concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant . The impact of gender and smoking was also investigated . Twenty-six patients were included in the study . Of 167 implants , 24 failed . The implant estimated survival rate was 85 % at the end of the follow-up . There was no significant difference between smokers and non-smokers or genders concerning implant survival . Marginal bone loss was 2.5 , 2.9 , 3.0 and 3.1 mm from the implant-abutment junction , after 1 , 2 , 5 and 10 years , respectively . The bone level stabilised after 2 years . This technique results in good facial morphology , good oral function and aesthetics . All patients are still wearing their original fixed bridges PURPOSE This prospect i ve investigation studied the clinical and radiographic performance of m and ibular fixed prostheses supported by osseointegrated implants over more than 20 years . MATERIAL S AND METHODS A total of 273 st and ard Brånemark implants ( 10 mm long ) were placed in 47 patients between 1978 and 1982 . Clinical and radiographic data collected at several examinations over the 20-year observation period have been reported previously . This study presents the outcome of the latest follow-up after 20 to 23 years . RESULTS Thirty patients ( 64 % ; 75 % of those still alive ) attended the 20-year follow-up examination . Three implants were lost during the entire observation period , and the 20-year implant cumulative survival rate was 98.9 % . All patients had continuous prosthesis function , but two had their m and ibular prostheses remade during the 20 years . No implants or prostheses were lost or fractured during the last 5 years , and only a few prosthodontic complications were noted . The mean bone level was 1.6 mm ( SD 0.90 ) below the reference point after 20 years , and mean bone loss was 0.2 mm ( SD 0.22 ) between the 15- and 20-year follow-ups . Thirty-seven implants ( 24 % ) showed more than two exposed threads at the 15-year follow-up examination , but only four implants ( 3 % ) presented pain and /or bone loss exceeding one thread ( 0.6 mm ) during the last 5 years . CONCLUSION The successful treatment result after 15 years continued up to more than 20 years in function . During the last 5 years , a majority of the implants with several exposed implant threads could be maintained without any complications , and the frequency of implants showing signs of ongoing peri-implantitis was less than 3 % The aim of this prospect i ve r and omized controlled clinical trial was to evaluate the clinical outcomes and prosthetic aftercare of edentulous patients with a m and ibular overdenture retained by two IMZ implants or two Brånemark implants during a 10-year period . Patients were allocated to the IMZ group ( n=29 ) or the Brånemark group ( n=32 ) by a computerized balancing method . In the IMZ group , four implants were lost during the 10-year follow-up ( survival rate : 93 % ) . In the Brånemark group , nine implants were lost ( survival rate : 86 % ) . All patients were re-operated successfully . Multiple prosthetic revisions were necessary in both groups ; especially the precision attachment system in the overdenture ( 23 % of the total number of revisions ) and the denture base and teeth ( 26 % of the total number of revisions ) were subject to frequent fracture . From this study , it can be concluded that both the IMZ implant and the Brånemark implant systems supporting an overdenture are functioning well after 10 years of follow-up . There are no indications of a worsening of clinical or radiographical state after 10 years OBJECTIVES The aim of this prospect i ve comparative study was to evaluate the survival rate , condition of peri-implant tissues , patient satisfaction and surgical and prosthetic aftercare of the IMZ-implant system ( two-stage cylinder type ) , the Brånemark-implant system ( two-stage screw type ) and the ITI-implant system ( one-stage screw type ) supporting a m and ibular overdenture during a 10-year follow-up period . MATERIAL S AND METHODS Three groups of 30 edentulous patients were treated with two endosseous implants in the interforaminal region of the m and ible . Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment and after 1 , 5 and 10 years of functional loading . Prosthetic and surgical aftercare was scored during the evaluation period , as well as patient satisfaction . RESULTS The 10-year survival rate was 93 % for the IMZ group , 98 % for the Brånemark group and 100 % for the ITI group ( IMZ < ITI , p<0.05 ) . Mean marginal bone loss was limited over a period of 10 years . No differences in satisfaction and aftercare were observed between the groups . CONCLUSION It is concluded that two implants placed in the interforaminal region , connected with a bar , supply a proper base for the support of a m and ibular overdenture in the edentulous patient . After10 years , no relevant changes had developed between the three implant systems OBJECTIVES The aim of this study was to evaluate and compare marginal bone loss and clinical outcomes of conventionally and immediately loaded two implants supporting a ball-retained m and ibular overdenture . MATERIAL S AND METHODS Thirty six completely edentulous patients ( 22 males and 14 females ) were r and omly assigned into two groups . Each patient received two implants in the canine area of the m and ible after a minimal flap reflection . Implants were loaded by m and ibular overdentures either 3 months ( conventional loading group ) or the same day ( immediate loading group ) after implant placement . Ball attachments were used to retain all overdentures to the implants . Vertical and horizontal alveolar bone losses were evaluated in both groups 1 and 3 years after implant placement using multislice computed tomography , which allow evaluation of peri-implant buccal and lingual alveolar bone . Plaque scores , gingival scores , probing depths and periotest values ( PTVs ) were evaluated at 4 months ( baseline ) , 1 and 3 years after implant placement . Clinical and radiographic evaluations were performed at distal , labial , mesial and lingual peri-implant sites . RESULTS After 3 years of follow-up period , the immediate loading group recorded significant vertical bone loss at distal and labial sites than the conventional loading group and no significant differences in horizontal bone loss between groups were observed . Probing depth at distal and labial sites in the immediate loading group were higher than the conventional loading group , while plaque scores , gingival scores and PTVs showed no significant differences between the two groups . A low level of positive correlation between plaque scores , gingival scores , probing depths and vertical bone loss was noted . CONCLUSION Immediately loaded two implants supporting a ball-retained m and ibular overdenture are associated with more marginal bone resorption and increased probing depths when compared with conventionally loaded implants after 3 years . The bone resorption and probing depths at distal and labial sites are significantly higher than those at mesial and lingual sites . Clinical outcomes do not differ significantly between loading protocol STATEMENT OF PROBLEM Distinct clinical parameters determine whether fixed or removable implant-supported prostheses are indicated to restore the edentulous maxilla . However , there is a strong belief that fixed implant prostheses meet with greater patient acceptance and satisfaction , but this may differ from the patients ' perceptions , their psychological responses to treatment , and their assessment s of the treatment outcome . PURPOSE This prospect i ve clinical study compared the treatment outcomes of fixed and removable implant-supported restorations in the edentulous maxilla with the main emphasis on the patient 's point of view . MATERIAL AND METHODS Twenty patients who requested an implant-supported superstructure to restore the edentulous maxilla were asked to complete a question naire measuring their satisfaction with the present situation and the psychologic impact of their oral health status with their responses marked on a Visual Analog Scale ( VAS ) . Ten patients were treated with a fixed , screw-retained implant prosthesis ( group 1 ) , and 10 were treated with a removable , implant-supported and bar-retained overdenture ( group 2 ) . Six months after prosthetic rehabilitation , patients were again given the question naire to assess their psychologic well-being and satisfaction with the implant-supported restoration . RESULTS Both prosthesis design s were associated with significant improvements in comfort and retention , function , esthetics and appearance , taste , speech , and self-esteem . No difference was found between the 2 groups with respect to how the patients assessed the implant therapy . However , the results indicated that patients in group 2 experienced greater differences between pretreatment and posttreatment scores for the parameters esthetics , taste , and speech . Treatment costs per unit were significantly higher in group 1 than in group 2 . CONCLUSION Patients in groups 1 and 2 were similarly satisfied with their implant-supported prostheses in the edentulous maxilla with regard to their well-being and the cost-utility , irrespective of whether the restoration was fixed or removable The aim of this study was to evaluate the clinical function and long-term prognosis of overdentures retained by a small number of implants in the maxilla and m and ible using one of two different attachment systems . Included in the study were all patients referred to specialty clinics in Jönköping and Linköping , Sweden , during the treatment period who needed an overdenture and could be provided with a minimum number of two bilaterally-placed implants . Excluded were patients with bone-grafted jaws , irradiated cancer patients , heavy bruxers , and patients who had lost a fixed prosthesis because of implant losses . The patients were r and omly assigned to receive one retentive system , either a round 2-mm-diameter bar with clips or ball attachments ( Nobel Biocare ) . Eighteen overdentures were placed in maxillae and 32 in m and ibles , supported by a total of 115 Brånemark implants . Of the implants placed , 86.1 % were continuously osseointegrated . The cumulative implant survival rates after 7 years of loading were 75.4 % in the maxillae and 100 % in the m and ibles . There was no difference in implant survival rate between the attachment systems . Patients with implant losses were characterized by severely resorbed maxillary ridges and inferior bone quality , together with unfavorable loading circumstances such as short implants combined with long leverages . Complications and prosthetic adjustments were mostly resolved early and easily PURPOSE The aim of this study was to compare definitive acrylic resin prostheses with or without a cast metal framework that were immediately loaded and supported by axial and tilted implants in completely edentulous patients after 3 years of function . MATERIAL S AND METHODS Patients who were completely or partially edentulous in one or both arches with severe atrophy of the posterior regions were selected for this study . All patients immediately received prosthetic rehabilitations , each supported by four implants ( two axial and two tilted ) . The patients were r and omized to receive a definitive prosthesis with a cast metal framework or one made of acrylic resin only . Follow-up visits were performed up to 36 months after implant insertion and included radiographic assessment s of bone levels around the implants . RESULTS Thirty-six patients participated , and 44 complete-arch immediately loaded prostheses ( 24 maxillary and 20 m and ibular ) , each supported by four implants ( in total 176 implants ) , were placed . In all , 21 screw-retained full-arch acrylic resin prostheses and 23 cast-metal-framework prostheses were delivered to the patients . The 3-year overall implant survival rate was 100 % for axially positioned implants and 96.59 % for tilted implants . Implant survival rates were 98.96 % in the maxilla and 97.5 % in the m and ible . None of the 44 fixed prostheses were lost during the observation period , representing a prosthetic survival rate of 100 % . No statistically significant differences were seen in crestal bone loss between tilted and axial implants at 12 , 24 , and 36 months in either arch . CONCLUSIONS The same clinical outcome was seen for patients treated with the so-called All on Four protocol , regardless of whether the acrylic resin restorations were reinforced with metal BACKGROUND No long-term clinical studies covering more than 5 years are available on Computer Numeric Controlled ( CNC ) milled titanium frameworks . AIM To evaluate and compare the clinical and radiographic performance of implant-supported prostheses provided with CNC titanium frameworks in the edentulous jaw with prostheses with cast gold-alloy frameworks during the first 10 years of function . MATERIAL AND METHODS Altogether , 126 edentulous patients were by r and om provided with 67 prostheses with titanium frameworks ( test ) in 23 maxillas and 44 m and ibles , and with 62 prostheses with gold-alloy castings ( control ) in 31 maxillas and 31 m and ibles . Clinical and radiographic 10-year data were collected for the groups and statistically compared on patient level . RESULTS The 10-year prosthesis and implant cumulative survival rate was 95.6 % compared with 98.3 % , and 95.0 % compared with 97.9 % for test and control groups , respectively ( p > .05 ) . No implants were lost after 5 years of follow-up . Smokers lost more implants than nonsmokers after 5 years of follow-up ( p < .01 ) . Mean marginal bone loss in the test group was 0.7 mm ( SD 0.61 ) and 0.7 mm ( SD 0.85 ) in the maxilla and m and ible , with similar pattern in the control group ( p > .05 ) , respectively . One prosthesis was lost in each group due to loss of implants , and one prosthesis failed due to framework fracture in the test group . Two metal fractures were registered in each group . More appointments of maintenance were needed for the prostheses in the maxilla compared with those in the m and ible ( p < .001 ) . CONCLUSION The frequency of complications was low with similar clinical and radiological performance for both groups during 10 years . CNC-milled titanium frameworks are a viable alternative to gold-alloy castings for restoring patients with implant-supported prostheses in the edentulous jaw PURPOSE The aim of the present study was to evaluate the periimplant conditions and the maintenance requirements for implant-supported overdentures in the m and ible retained with ball or bar attachments during a 5-year period . MATERIAL S AND METHODS Twenty-six completely edentulous patients had two Astra Tech dental implants placed in the anterior part of the m and ible . The denture attachment system for the patients was chosen r and omly by drawing lots . Eleven patients drew the bar attachment system and fifteen patients drew the ball attachment system . Plaque Index , Gingival Index , and probing pocket depth were assessed around each implant . Periotest values were recorded , and periodically identical intraoral radiographs were obtained with a specially design ed film-holding device . RESULTS No implants were lost from baseline to the 5-year registration . The periimplant conditions were very healthy after 5 years . No significant differences of the periimplant variables were recorded between the bar and the ball groups . During the first year of function , significantly more complications/repairs were registered in the bar group than in the ball group . In the following years , no significant differences were registered . The mean frequency of complications/repairs per patient per year was 1.0 in the bar group and 0.6 in the ball group during the 5-year observation period . CONCLUSION Two implants with ball or bar attachment supported an overdenture in the m and ible for 5 years with a 100 % survival rate . No differences in marginal bone loss or health of the periimplant mucosa were observed between bar and ball attachment , but the frequency of technical complications/repairs per patient was higher around bar than ball attachments PURPOSE This prospect i ve study was performed to evaluate the outcomes of XiVE ® S plus implants ( Dentsply Friadent , Mannheim , Germany ) following conventional restoration with bar structures and overdentures in the edentulous m and ible . MATERIAL S AND METHODS A total of 39 patients were treated with four interforaminal implants ( n = 156 ) splinted by a Dolder bar . Overdentures were attached to the bars after 3 months of healing . As primary outcome measures , clinical and radiological parameters were evaluated at the time of implant placement ( baseline ) and once a year ( 1 , 2 , 3 , 4 , 5 years ) after functional loading . Secondary outcome measures included ( i ) primary stability and surgical complications , as well as ( ii ) Periotest ® ( Medizintechnik Gulden , Modautal , Germany ) values , implant survival , and prosthetic complications at baseline and follow-up . RESULTS A total of 156 implants were placed . The vast majority ( n = 149 ) were tightened to > 30 Ncm , while torques in the range of 20 - 30 Ncm were obtained in the remaining cases ( n = 7 ) . Mean crestal bone levels around the implants were 0.41 mm at baseline and 1.04/1.20/1.34/1.45/1.44 mm after 1/2/3/4/5 years respectively . The mean values of the plaque , calculus , bleeding , and mucosal indices remained low throughout this period . The reported follow-up periods involved one implant loss after 3 months ( survival rate : 99.4 % ) and one implant failure after 4 years ( success rate : 98.4 % ) . Prosthetic complications included factures of bars ( n = 3 ) and denture teeth ( n = 7 ) . Prosthetic survival was 100 % . CONCLUSIONS Dolder bars to restore oral implants in the edentulous m and ible appear to offer a high rate of implant survival , good stability of the peri-implant tissue , and a low rate of prosthetic complications This report presents the results of a 5-year prospect i ve multicenter study including nine centers worldwide . A total of 30 patients received 117 Brånemark implants in the maxillae , and 103 patients received 393 implants in the m and ibles . According to the protocol , all integrated maxillary implants were to be loaded ; however , only two of four m and ibular implants were planned for support of the overdentures , leaving the remaining implants covered by mucosa as backup for possible implant failures . Thirty-five patients ( 26.3 % ) who were provided with 127 implants ( 24.9 % ) were withdrawn from the study . Six patients treated in the maxilla lost all their implants and resumed wearing complete dentures . The cumulative success rates for implants and for overdentures supported by two implants in the edentulous m and ible were 94.5 % and 100 % , respectively . The corresponding cumulative success rates for implants and for overdentures supported by an optimal number of implants in the maxilla were 72.4 % and 77.9 % , respectively . Significantly better jawbone characteristics at the time of implant surgery were considered to contribute to the better cumulative success rates in the m and ibles . Mean marginal bone loss was 0.8 mm ( SD 0.8 ) and 0.5 mm ( SD 0.8 ) for loaded implants during a 5-year period of time in the maxillae and m and ibles , respectively . Measurements of the clinical height of the abutment cylinders indicated a mean recession ( 0.2 mm ) of peri-implant mucosa during the follow-up period in the m and ibles . Conversely , hyperplasia was observed in the maxillae BACKGROUND Documentation of early loading of m and ibular overdentures supported by different implant systems is scarce . PURPOSE This study aim ed to compare the biologic and prosthetic outcome of m and ibular overdentures supported by unsplinted early-loaded one- and two-stage oral implants after 5 years of function . MATERIAL S AND METHODS Twenty-eight consecutive patients were screened following an inclusion and exclusion criteria , and r and omly allocated to treatment groups . Ball-retained m and ibular overdentures were fabricated on two unsplinted Straumann ( Institut Straumann AG , Basel , Switzerl and ) and Brånemark ( Nobel Biocare AB , Göteborg , Sweden ) dental implants and subjected to an early-loading protocol . During the 5-year period , prosthetic complications were recorded . At 5-years of function , plaque , peri-implant inflammation , bleeding , and calculus index scores were recorded , and st and ard periapical radiographs were obtained from each implant for measurement of marginal bone loss . RESULTS All implants survived during the observation period . The peri-implant inflammation , bleeding , and calculus index scores around Straumann and Brånemark implants were similar ( p > .05 ) . The marginal bone loss around Brånemark implants ( 1.21 + /- 0.1 ) was higher than Straumann implants ( 0.73 + /- 0.06 ) at 5 years of function ( p = .002 ) . Kaplan-Meier tests revealed that 1- and 5-year survival of overdentures on Straumann and Brånemark implants were similar ( p = .85 ) . Wear of the ball abutment in the Brånemark group was higher than in the Straumann group ( p < .05 ) . Complications regarding the retainer and the need for occlusal adjustments were higher in the Straumann group ( p < .05 ) . Chi-square test revealed that the frequency of retightening of the retainer was higher in the Straumann group than in the Brånemark group ( p < .05 ) . CONCLUSIONS M and ibular overdentures supported by unsplinted early-loaded Straumann and Brånemark implants lead to similar peri-implant soft tissue and prosthetic outcomes , although higher marginal bone loss could be observed around Brånemark implants after 5 years PURPOSE The purpose of this study is to evaluate prospect ively survival and success rates of implants placed in the interforaminal area of edentulous m and ibles and immediately loaded with an implant-supported overdenture . MATERIAL S AND METHODS Eighty-two patients , 33 males and 49 females , aged between 42 and 87 years ( mean age 58.6 yr ) , presenting edentulous m and ibles were rehabilitated with an implant-supported overdenture in the m and ible . Three hundred twenty-eight screw-type osseointegrated implants ( 164 Ha-Ti , Mathys Dental , Bettlach , Switzerl and ; 84 ITI Dental Implant System , Straumann Institute , Waldenburg , Switzerl and ; 40 Brånemark Conical , Nobel Biocare AB , Gothenburg , Sweden ; 40 Frialoc , Friatec , AG Mannheiti , Germany ) , were placed in the intraforaminal area of the mental symphysis ( 4 implants per patient ) . Immediately after implant placement , a U-shaped gold or titanium bar was fabricated and implants were rigidly connected with the bar and immediately loaded with an implant-retained overdenture . Success rate of implants was evaluated clinical ly and radiographically every year after the loading of the prostheses according to the following parameters : ( 1 ) absence of clinical mobility of implants tested individually after bar removal , ( 2 ) absence of periimplant radiolucency evaluated on panoramic radiographs , ( 3 ) absence of pain and radiologic or clinical signs of neural lesion , and ( 4 ) periimplant bone resorption mesial and distal to each implant less than 0.2 mm after the first year of prosthetic load . RESULTS Of 328 implants placed , 296 were followed up from a minimum of 36 months to a maximum of 96 months , with a mean follow-up of 62 months . Seven implants in 6 different patients were removed owing to loss of osseointegration , whereas 18 implants , although still osseointegrated , did not fulfill success criteria due to bone resorption > 0.2 mm/year after the first year of loading . Despite implant losses , all patients maintained their bars supporting overdentures , although in 6 patients they were supported by 3 instead of 4 implants . The only patient who lost 2 implants received 2 new implants , which survived normally . Therefore , the absolute success and survival rates were 91.6 % and 97.6 % , respectively , whereas the cumulative survival and success rates of implants obtained with a life table analysis were 96.1 % and 88.2 % , respectively . CONCLUSIONS Results of this study seem to demonstrate that survival and success rates of immediately loaded implants placed in the intraforaminal area of the m and ible and rigidly connected with a bar through an implant-supported overdenture are consistent with those reported in the international literature as far as delayed loading is concerned after 3 years of loading . After longer observation times , this study demonstrated that , while survival rates of implants and bar-supported overdentures are still consistent with results published in the international literature pertaining to delayed loading , a moderate decrease in success rates of implants was found . Nevertheless , it must be stressed that this decrease ( 88.8 and 90.4 % after a 7- to 8-year observation period for Ha-Ti and ITI implants ) is related only to two implant systems ; no data are available for the other two implant systems because of the shorter follow-up period The prosthodontic methods and outcomes of treating 127 patients in nine centres over a period of 5 years is described . The benefits perceived by patients and the changes induced in the denture-bearing tissues and temporom and ibular joints are reported . To sustain effective treatment outcomes , the levels of maintenance needed by the overdentures are contrasted for restoration of the edentulous m and ibles and maxillae BACKGROUND The aim of this study was to evaluate the feasibility of using a two-piece implant system in a non-submerged procedure and to study the impact of the microgap between the implant and abutment . METHODS Sixty edentulous patients ( Cawood Class V-VI ) participated in this study . After r and omization , 20 patients received two two-piece implants placed in a non-submerged procedure , 20 patients received two two-piece implants placed in the traditional submerged procedure , and 20 patients were treated with two one-piece dental implants placed in the traditional non-submerged procedure . The implants were placed in the m and ible for overdenture treatment . A st and ardized clinical evaluation was performed and radiographs were taken immediately after denture insertion and yearly up to 5 years . Peri-implant sample s were collected 12 , 36 , and 60 months after loading with sterile paper points and analyzed for the presence of putative periodontal pathogens using culture techniques . RESULTS One two-piece implant of the non-submerged group and one two-piece implant of the submerged group were lost after 6 and 12 months , respectively . After 5 years of functioning , no significant clinical , radiological , or microbiological differences were found between the three groups . No association was found between the level of the microgap and the amount of bone loss . CONCLUSIONS The results of this study indicate that dental implants design ed for a submerged implantation procedure can also be used in a non-submerged procedure and may be as predictable as when used in a submerged procedure or as one-piece implants . The microgap at the crestal level in two-piece implants does not appear to have an adverse effect on the amount of peri-implant bone loss PURPOSE To evaluate telescopic crown ( TC ) , bar , and locator attachments used in removable four implant-supported overdentures for patients with edentulous maxillae . MATERIAL S AND METHODS A total of 30 maxillary edentulous patients were enrolled in a 3-year prospect i ve study . Ten patients ( group A ) were treated with overdentures supported by TCs , 10 patients ( group B ) with overdentures supported by bar attachments , and 10 patients ( group C ) with overdentures supported by locator attachments . A total of 120 implants were used to restore oral function . During the 3-year follow-up period , implant survival and success rates , biologic and mechanical complications , prosthodontic maintenance efforts , and patient satisfaction were evaluated . RESULTS All 30 patients were available for the 3-year follow-up and exhibited 100 % implant survival and success rates . Peri-implant marginal bone resorption was not statistically significant for the three groups . There were lower plaque , bleeding , gingiva , and calculus indices in group C compared with groups A and B. The number of prosthodontic maintenance visits revealed eight complications in the TC group , seven complications in the bar group , and four complications in the locator group . However , there were no differences in the clinical effects of the overdentures in the three groups . CONCLUSION Within the limits of this prospect i ve study , it was concluded that the locator system produced superior clinical results compared with the TC and bar attachments in terms of peri-implant hygiene parameters , the frequency of prosthodontic maintenance measures , cost , and ease of denture preparation . However , longer-term prospect i ve studies are required to confirm these results |
2,182 | 26,325,263 | There appears to be a prevalence of 581 G above which IPTp-SP no longer protects against LBW . | OBJECTIVES To estimate where intermittent preventive treatment ( IPTp ) using sulphadoxine-pyrimethamine ( SP ) could be withdrawn as an intervention due to declining malaria transmission intensity , or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581 G . | Background In Malawi , there has been a return of Plasmodium falciparum sensitivity to chloroquine ( CQ ) since sulfadoxine-pyrimethamine ( SP ) replaced CQ as first line treatment for uncomplicated malaria . When used for prophylaxis , Amodiaquine ( AQ ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa . Here we compare the efficacy , safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria . Methodology and Findings 455 children aged 1–5 years were recruited into a double-blinded r and omised trial comparing SP to the three combination therapies . Using intention to treat analysis with missing outcomes treated as successes , and without adjustment to distinguish recrudescence from new infections , the day 28 adequate clinical and parasitological response ( ACPR ) rate for SP was 25 % , inferior to each of the three combination therapies ( p<0.001 ) . AQ+SP had an ACPR rate of 97 % , higher than CQ+SP ( 81 % ) and ART+SP ( 70 % ) , p<0.001 . Nineteen children developed a neutropenia of ≤0.5 × 103 cells/µl by day 14 , more commonly after AQ+SP ( p = 0.03 ) . The mutation pfcrt 76 T , associated with CQ resistance , was detected in none of the pre-treatment or post-treatment parasites . The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP , p = 0.002 . Conclusions The combination AQ+SP was highly efficacious , despite the low efficacy of SP alone ; however , we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment . This study confirms the return of CQ sensitivity in Malawi and importantly , shows no evidence of the re-emergence of pfcrt 76 T after treatment with CQ or AQ . Given the safety record of AQ when used as a prophylaxis , our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny . Trial Registration Controlled-Trials.com IS RCT Background Sulphadoxine-pyrimethamine ( SP ) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy , is being investigated for intermittent preventive treatment of malaria in infants ( IPTi ) . High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes . This study compared the in vivo efficacy of SP in symptomatic 6–59 month children with uncomplicated malaria and in asymptomatic 2–10 month old infants . Methodology and Principal Findings An open label single arm ( SP ) st and ard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants . Enrolment was stopped early ( 87 in the symptomatic and 25 in the asymptomatic studies ) due to the high failure rate . Molecular markers were examined for recrudescence , re-infection and markers of drug resistance and a review of literature of studies looking for the 581 G dhps mutation was carried out . In symptomatic children PCR-corrected early treatment failure was 38.8 % ( 95 % CI 26.8–50.8 ) and total failures by day 28 were 82.2 % ( 95 % CI 72.5–92.0 ) . There was no significant difference in treatment failures between asymptomatic and symptomatic children . 96 % of sample s carried parasites with mutations at codons 51 , 59 and 108 in the dhfr gene and 63 % carried a double mutation at codons 437 and 540 . 55 % carried a third mutation with the addition of a mutation at codon 581 in the dhps gene . This triple : triple haplotype maybe associated with earlier treatment failure . Conclusion In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful . The study found a new combination of parasite mutations that maybe associated with increased and earlier failure . Trial Registration Clinical Trials.gov Intermittent preventive treatment in pregnancy ( IPTp ) is used to prevent Plasmodium falciparum malaria . However , parasites resistant to the IPTp drug sulfadoxine-pyrimethamine ( SP ) have emerged worldwide , and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice . In a prospect i ve delivery cohort in Muheza , Tanzania , we examined the effects of SP IPTp on parasite resistance alleles , parasite diversity , level of parasitemia , and inflammation in the placenta . IPTp use was associated with an increased fraction of parasites carrying the resistance allele at DHPS codon 581 , an increase in the level of parasitemia , and more intense placental inflammation . The lowest mean level of parasite diversity and highest mean level of parasitemia occurred in women after recent IPTp use . These findings support a model of parasite release and facilitation , whereby the most highly resistant parasites out-compete less fit parasite population s and overgrow under drug pressure . Use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance OBJECTIVE To assess the efficacy at individual level of intermittent preventive treatment with sulfadoxine-pyrimethamine ( IPTp-SP ) in primi- and secundigravidae in rural Burkina Faso . METHODS Data of 1441 women enrolled in a health centre r and omized trial and delivering a live-singleton between September 2004 and October 2006 were analysed at individual level . Prevalence of peripheral and placental parasitaemia , anaemia ( PCV < 33 % ) , low-birth weight ( < 2500 g ; LBW ) , mean packed cell volume ( PCV ) and birth weight were compared in relation to the number of directly observed SP doses . RESULTS Two or more doses of SP significantly reduced the risk of placental parasitaemia [ adjusted odds ratio ( AOR ) = 0.04 , 95%CI = 0.003 - 0.60 , P = 0.023 ] and anaemia at delivery ( AOR = 0.31 , 95%CI = 0.18 - 0.52 , P < 0.001 ) . IPTp was associated with reduced risk of LBW in primigravidae ( AOR = 0.11 , 95%CI = 0.07 - 0.17 , P < 0.001 ) but not secundigravidae ( AOR = 0.70 , 95%CI = 0.26 - 1.91 , P = 0.452 ) . For each increment in number of SP doses mean PCV increased by 1.0 % ( 95%CI = 0.4 - 1.7 , P = 0.005 ) at 32 weeks gestation , by 1.2 % ( 95%CI = 0.2 - 2.2 , P = 0.025 ) at delivery and mean birth weight by 220 g ( 95%CI = 134 - 306 P < 0.001 ) in primigravidae and by 102 g ( 95%CI = 55 - 148 , P = 0.001 ) in secundigravidae . CONCLUSION The risk of malaria infection was significantly reduced by IPTp with SP in primi- and secundigravidae in rural Burkina Faso . The impact on clinical outcomes is lower and mainly limited to primigravidae for LBW . Incomplete uptake of IPTp-SP and limited effect in low risk groups together may substantially dilute the measurable impact of effective interventions . This needs to be taken into account when evaluating interventions at community level Abstract .The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia ( PCP ) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus . All patients had a CD4 + T-lymphocyte count of less than 100 cells/μl at study entry . Efficacy in this single-arm open-label prospect i ve study was analyzed on an as-treated basis . No patient received highly active antiretroviral treatment , including protease inhibitors or non-nucleoside reverse transcriptase inhibitors , while on study medication . PCP developed in four patients , one of whom had been noncompliant . No PCP episode occurred in the first year . Probabilities of freedom from PCP were 0.97 ( 95%CI , 0.92–1 ) after 24 months and 0.93 ( 95%CI , 0.84–1 ) after 36 months . Of 74 ( 69.8 % ) patients positive for anti-toxoplasma IgG antibodies , one noncompliant patient developed toxoplasmic encephalitis after 24 months . Allergic reactions were observed in 18 ( 17 % ) patients and result ed in permanent discontinuation in 7 ( 6.6 % ) patients . One ( 0.9 % ) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction ( Stevens-Johnson syndrome ) . The median survival of study participants was 29 months , with relentless progression of AIDS accounting for most deaths . The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis . Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted . Rechallenge frequently results in tolerance . Efficacy and safety compare favorably with previously studied regimens . This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens This study examines the relationship between malaria treatment failure after sulfadoxine-pyrimethamine ( S-P ) chemotherapy and presence of mutations in the Plasmodium falciparum dihydropteroate synthase ( dhps ) and dihydrofolate reductase ( dhfr ) genes ( associated with resistance in vitro to S and P ) before treatment . In Kenya , 38 malaria patients in a holoendemic area , and 21 in an epidemic area , participated in the trial in 1997 - 98 . In the 2 areas , drug failure occurred in 76 % and 75 % of cases where any mutation in dhfr was seen ( positive predictive values 76 % and 75 % : P = 0.003 and 0.008 ) and an identical association was seen with dhfr Asn-108 . In the holoendemic area all occurrences of > or = 2 mutations in dhfr predicted drug failure . Only 3 instances were seen in the epidemic focus , but treatment failed in all . Only in the epidemic focus , 7 ( 88 % ) of 8 occurrences of > or = 1 mutations in dhps , and all occurrences of the Gly-437 allele of dhps , predicted failure . Association between mutations in dhps and mutations in dhfr was noted in the combined sites , irrespective of outcome . Although this makes the relationship of combined dhfr and dhps mutations to failure more difficult to interpret , it nevertheless supports S-P selection acting on both genes . In the holoendemic site , treatment success increased with age . In this location , acquired immunity may mask the impact of mutations in dhps , since sulfadoxine is a less effective treatment than pyrimethamine ABSTRACT Antifolate drugs have an important role in the treatment of malaria . Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs , respectively . Rw and a has the highest levels of antimalarial drug resistance in Africa . We correlated the efficacy of chlorproguanil-dapsone plus artesunate ( CPG-DDS+A ) and amodiaquine plus sulfadoxine-pyrimethamine ( AQ+SP ) in children with uncomplicated malaria caused by Plasmodium falciparum parasites with pfdhfr and pfdhps mutations , which are known to confer reduced drug susceptibility , in two areas of Rw and a. In the eastern province , where the cure rates were low , over 75 % of isolates had three or more pfdhfr mutations and two or three pfdhps mutations and 11 % had the pfdhfr 164-Leu polymorphism . In the western province , where the cure rates were significantly higher ( P < 0.001 ) , the prevalence of multiple resistance mutations was lower and the pfdhfr I164L polymorphism was not found . The risk of treatment failure following the administration of AQ+SP more than doubled for each additional pfdhfr resistance mutation ( odds ratio [ OR ] = 2.4 ; 95 % confidence interval [ CI ] = 1.01 to 5.55 ; P = 0.048 ) and each pfdhps mutation ( OR = 2.1 ; 95 % CI = 1.21 to 3.54 ; P = 0.008 ) . The risk of failure following CPG-DDS+A treatment was 2.2 times higher ( 95 % CI = 1.34 to 3.7 ) for each additional pfdhfr mutation , whereas there was no association with mutations in the pfdhps gene ( P = 0.13 ) . The pfdhfr 164-Leu polymorphism is prevalent in eastern Rw and a. Antimalarial treatments with currently available antifol-sulfa combinations are no longer effective in Rw and a because of high-level resistance Intermittent preventive treatment of malaria during pregnancy ( IPTp ) and insecticide-treated nets ( ITN ) are recommended malaria interventions during pregnancy ; however , there is limited information on their efficacy in areas of low malaria transmission in sub-Saharan Africa . An individually-r and omised placebo-controlled trial involving 5775 women of all parities examined the effect of IPTp , ITNs alone , or ITNs used in combination with IPTp on maternal anaemia and low birth weight ( LBW ) in a highl and area of southwestern Ug and a. The overall prevalence of malaria infection , maternal anaemia and LBW was 15.0 % , 14.7 % and 6.5 % , respectively . Maternal and fetal outcomes were generally remarkably similar across all intervention groups ( P>0.05 for all outcomes examined ) . A marginal difference in maternal haemoglobin was observed in the dual intervention group ( 12.57g/dl ) compared with the IPTp and ITN alone groups ( 12.40g/dl and 12.44g/dl , respectively ; P=0.04 ) , but this was too slight to be of clinical importance . In conclusion , none of the preventive strategies was found to be superior to the others , and no substantial additional benefit to providing both IPTp and ITNs during routine antenatal services was observed . With ITNs offering a number of advantages over IPTp , yet showing comparable efficacy , we discuss why ITNs could be an appropriate preventive strategy for malaria control during pregnancy in areas of low and unstable transmission ABSTRACT A total of 252 children were enrolled in a drug trial to assess the effect of minimal doses of sulfadoxine ( Sdx ) and pyrimethamine ( Pyr ) . Parasite sample s isolated from these patients were analyzed before and after treatment to investigate the level of drug-resistant strains . The parasite genes encoding dihydrofolate reductase ( DHFR ) and dihydropteroate synthase ( DHPS ) were assayed for point mutations that are associated with resistance against drugs . Before treatment , Pyrr genotypes of the DHFR gene were found in 42 % of all sample s , 8 % of the patients harbored a mixed parasite population and 50 % had a sensitive DHFR genotype . In terms of the DHPS gene , we found mutations in 45 % of the parasites . Twenty-four percent had a Ser436 mutation , and 26 % had a Gly437mutation . Recrudescent parasites were highly enriched for both Pyrr and Sdxr strains after treatment ( P < 0.001 and P = 0.029 , respectively ) BACKGROUND Trimethoprim-sulfamethoxazole ( TS ) prophylaxis is recommended for persons living with human immunodeficiency virus infection and acquired immunodeficiency syndrome in Africa . TS and the antimalarial combination sulfadoxine-pyrimethamine ( SP ) share mechanisms of action and resistance patterns , and concerns about the impact of TS resistance on SP efficacy have contributed to reluctance to implement TS prophylaxis in Africa . METHODS To determine whether TS prophylaxis impairs SP efficacy for treatment of uncomplicated falciparum malaria , we conducted a r and omized , controlled , open-label study of TS prophylaxis . Two hundred and forty children 5 - 15 years old were r and omized in a 2 : 1 fashion to receive either thrice-weekly TS for 12 weeks or no prophylaxis and were treated with SP for subsequent episodes of malaria . The incidence of malaria , SP efficacy , and the prevalence of parasite mutations that confer antifolate drug resistance were measured . RESULTS TS prophylaxis had a 99.5 % protective efficacy against episodes of clinical malaria , with 97 % efficacy against infection . Four SP treatment failures occurred in the control group , and none occurred in the TS group . No evidence was seen for selection by TS of antifolate resistance-conferring mutations in parasite dihydrofolate reductase or dihydropteroate synthase during sub clinical infections . CONCLUSIONS In this setting of low antifolate resistance , TS was highly effective in preventing falciparum malaria infection and disease and did not appear to select for SP-resistant parasites |
2,183 | 29,734,210 | The present review did not find convincing evidence that these assumptions are valid .
There is , however , also no strong evidence that the assumptions are incorrect and /or that there is antagonistic activity between strains in a combination . | Probiotics are investigated as single-strain and multistrain products .
In the market , however , there is an increasing tendency to work with multistrain probiotics , in particular , products with a high number of different strains .
There are some thoughts behind this : more strains imply more chances of success ; it can mean a broader spectrum of efficacy , and there is often the hope that there are at least additive and , potentially , even synergistic effects . | Objectives . Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora , which may induce clinical symptoms , most commonly diarrhea . The severity of antibiotic-associated diarrhea may range from a brief , self-limiting disease to devastating diarrhea with electrolyte disturbances , dehydration , crampy abdominal pain , pseudomembranous colitis , toxic megacolon , or even death . The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear . In addition to more critical use of antimicrobials , adjunctive preventive measures to antibiotic-associated diarrhea are needed . The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months . Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG ( Lactobacillus GG ; American Type Culture Collection 53103 ) , a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea . Methods . Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital , Finl and , to 167 patients who were invited to participate in the study . Of the patients , 48 were lost to follow-up ; therefore , the final study population consisted of 119 children from 2 weeks to 12.8 years of age ( mean : 4.5 years ) . All study subjects met the inclusion criteria : they had not received any antimicrobial medication during the previous 3 months , they did not suffer from gastrointestinal disorders , and they did not need intravenous antimicrobial treatment . The patients were r and omized to receive placebo or 2 × 1010 colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment . Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste . The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months . Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days . In the case of diarrhea , viral ( adenovirus , rotavirus , calicivirus and astrovirus ) and bacterial ( Salmonella , Shigella , Yersinia , Campylobacter , Clostridium difficile , Staphylococcus aureus , and yeasts ) analyses were studied in fecal sample s. The metabolic activity of the gut microflora was assessed by analysis of fecal urease , β-glucosidase , and β-glucuronidase activities . The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment , because this period most likely reflects the effects of antimicrobial use . Secondary outcome measures were the activities of fecal urease , β-glucuronidase , and β-glucosidase . Results . On the entire follow-up , 80 % of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment . The incidence of diarrhea was 5 % in the Lactobacillus GG group and 16 % in the placebo group within 2 weeks of antimicrobial therapy ( χ2 = 3.82 ) . The treatment effect ( 95 % confidence interval ) of Lactobacillus GG was −11 % ( −21%–0 % ) . In diarrheal episodes , the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases . The age of the patients with diarrhea was between 3 months and 5 years in 75 % of cases in both groups . The severity of diarrhea was comparable in the study groups , as evidence d by similar stool frequency ( mean : 5 per day ; range : 3–6 ) and the duration of diarrhea ( mean : 4 days ; range : 2–8 ) . The activities of fecal urease and β-glucuronidase , but not β-glucosidase , changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike . The decrease in urease and β-glucuronidase activities was reversible in patients with no diarrhea , but in patients with diarrhea , the modifications in gut microflora were more profound and prolonged . The activities of the three enzymes were normalized within 3 weeks , evidence d by stable enzyme activities in sample s collected 3 weeks , 1 month , and 3 months after the beginning of the antimicrobial treatment , compared with those obtained before treatment . Discussion . In the present study , after a single antimicrobial treatment , the incidence of diarrhea was 16 % . The higher incidence of antibiotic-associated diarrhea in previous reports may be attributable to a recent antimicrobial therapy that disturbs intestinal flora and exposes to complications . Also , in the present study , changes in the metabolic activity of the intestinal flora were observed , evidence d by a transient decline in fecal enzyme activities . Different probiotic preparations , including lactobacilli , are recommended frequently to prevent antibiotic-associated diarrhea . Although probiotics have been shown to be efficient in the prevention and the treatment of viral gastroenteritis , their usefulness during antimicrobial therapy in children has not been eluci date d before . We observed that the administration of Lactobacillus GG to children receiving antimicrobial therapy for respiratory infection reduced the incidence of antibiotic-associated diarrhea to one third . The beneficial effect may be mediated by a number of functions of probiotics , ie , production of antimicrobial substances , local competition of adhesion receptors and nutrients , and stimulation of intestinal antigen specific and nonspecific immune responses . Conclusion . A probiotic strain , Lactobacillus GG , is effective in the prevention of diarrhea in children receiving antimicrobial treatment to respiratory infections Background & Aims Intestinal inflammation is a hallmark of cystic fibrosis ( CF ) . Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations . We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation . We also investigated the microflora structure before and after Lactobacillus GG ( LGG ) administration in children with CF with and without antibiotic treatment . Methods The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis ( DGGE ) , real-time polymerase chain reaction ( RT-PCR ) , and fluorescence in situ hybridization ( FISH ) . Intestinal inflammation was assessed by measuring fecal calprotectin ( CLP ) and rectal nitric oxide ( rNO ) production in children with CF as compared with healthy controls . We then carried out a small double-blind r and omized clinical trial with LGG . Results Twenty-two children with CF children were enrolled in the study ( median age , 7 years ; range , 2–9 years ) . Fecal CLP and rNO levels were higher in children with CF than in healthy controls ( 184±146 µg/g vs. 52±46 µg/g ; 18±15 vs. 2.6±1.2 µmol/L NO2 − , respectively ; P<0.01 ) . Compared with healthy controls , children with CF had significantly different intestinal microbial core structures . The levels of Eubacterium rectale , Bacteroides uniformis , Bacteroides vulgatus , Bifidobacterium adolescentis , Bifidobacterium catenulatum , and Faecalibacterium prausnitzii were reduced in children with CF . A similar but more extreme pattern was observed in children with CF who were taking antibiotics . LGG administration reduced fecal CLP and partially restored intestinal microbiota . There was a significant correlation between reduced microbial richness and intestinal inflammation . Conclusions CF causes qualitative and quantitative changes in intestinal microbiota , which may represent a novel therapeutic target in the treatment of CF . Administration of probiotics restored gut microbiota , supporting the efficacy of probiotics in reducing intestinal inflammation and pulmonary exacerbations . Trial Registration Clinical Trials.gov NCT Objective To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children . Design R and omised controlled clinical trial in collaboration with family paediatricians over 12 months . Setting Primary care . Participants Children aged 3 - 36 months visiting a family paediatrician for acute diarrhoea . Intervention Children 's parents were r and omly assigned to receive written instructions to purchase a specific probiotic product : oral rehydration solution ( control group ) ; Lactobacillus rhamnosus strain GG ; Saccharomyces boulardii ; Bacillus clausii ; mix of L delbrueckii var bulgaricus , Streptococcus thermophilus , L acidophilus , and Bifidobacterium bifidum ; or Enterococcus faecium SF68 . Main outcome measures Primary outcomes were duration of diarrhoea and daily number and consistency of stools . Secondary outcomes were duration of vomiting and fever and rate of admission to hospital . Safety and tolerance were also recorded . Results 571 children were allocated to intervention . Median duration of diarrhoea was significantly shorter ( P<0.001 ) in children who received L rhamnosus strain GG ( 78.5 hours ) and the mix of four bacterial strains ( 70.0 hours ) than in children who received oral rehydration solution alone ( 115.0 hours ) . One day after the first probiotic administration , the daily number of stools was significantly lower ( P<0.001 ) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups . The remaining preparations did not affect primary outcomes . Secondary outcomes were similar in all groups . Conclusions Not all commercially available probiotic preparations are effective in children with acute diarrhoea . Paediatricians should choose bacterial preparations based on effectiveness data . Trial registration number Current Controlled Trials IS RCT N56067537 Objective To estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children . Design and setting This was a multisite , r and omised , double-blind , placebo-controlled clinical trial conducted between September 2009 and 2012 . The study was conducted through general practice s and pharmacies in Launceston , Tasmania , Australia . Participants and interventions Children ( aged 1–12 years ) prescribed antibiotics , were r and omised to receive 200 g/day of either yogurt ( probiotic ) containing Lactobacillus rhamnosus GG ( LGG ) , Bifidobacterium lactis ( Bb-12 ) and Lactobacillus acidophilus ( La-5 ) or a pasteurised yogurt ( placebo ) for the same duration as their antibiotic treatment . Outcomes Stool frequency and consistency were recorded for the duration of treatment plus 1 week . Primary outcome was stool frequency and consistency , classified at different levels of diarrhoea severity . Due to the small number of cases of diarrhoea , comparisons between groups were made using Fisher 's exact analysis . Results 72 children commenced and 70 children ( 36 placebo and 34 probiotic ) completed the trial . There were no incidents of severe diarrhoea ( stool consistency ≥6 , ≥3 stools/day for ≥2 consecutive days ) in the probiotic group and six in the placebo group ( Fisher 's exact p=0.025 ) . There was also only one episode of minor diarrhoea ( stool consistency ≥5 , ≥2 stools/day for ≥2 days in the probiotic group compared to 21 in the placebo group ( Fisher 's exact p<0.001 ) . The probiotic group reported fewer adverse events ( 1 had abdominal pain , 1 vomited and 1 had headache ) than the placebo group ( 6 had abdominal pain , 4 had loss of appetite and 1 had nausea ) . Conclusions A yogurt combination of LGG , La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children . Trial registration number Australian New Zeal and Clinical Trials Registry Balanced glucose metabolism ensures optimal fetal growth with long-term health implication s conferred on both mother and child . We examined whether supplementation of probiotics with dietary counselling affects glucose metabolism in normoglycaemic pregnant women . At the first trimester of pregnancy 256 women were r and omised to receive nutrition counselling to modify dietary intake according to current recommendations or as controls ; the dietary intervention group was further r and omised to receive probiotics ( Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 ; diet/probiotics ) or placebo ( diet/placebo ) in a double-blind manner , whilst the control group received placebo ( control/placebo ) . Blood glucose concentrations were lowest in the diet/probiotics group during pregnancy ( baseline-adjusted means 4.45 , 4.60 and 4.56 mmol/l in diet/probiotics , diet/placebo and control/placebo , respectively ; P = 0.025 ) and over the 12 months ' postpartum period ( baseline-adjusted means 4.87 , 5.01 and 5.02 mmol/l ; P = 0.025 ) . Better glucose tolerance in the diet/probiotics group was confirmed by a reduced risk of elevated glucose concentration compared with the control/placebo group ( OR 0.31 ( 95 % CI 0.12 , 0.78 ) ; P = 0.013 ) as well as by the lowest insulin concentration ( adjusted means 7.55 , 9.32 and 9.27 mU/l ; P = 0.032 ) and homeostasis model assessment ( adjusted means 1.49 , 1.90 and 1.88 ; P = 0.028 ) and the highest quantitative insulin sensitivity check index ( adjusted means 0.37 , 0.35 and 0.35 ; P = 0.028 ) during the last trimester of pregnancy . The effects observed extended over the 12-month postpartum period . The present study demonstrated that improved blood glucose control can be achieved by dietary counselling with probiotics even in a normoglycaemic population and thus may provide potential novel means for the prophylactic and therapeutic management of glucose disorders Objective The purpose of this study was to evaluate the effectiveness of the probiotic Lactobacillus GG ( LGG ) in reducing the duration of acute infectious diarrhea in the pediatric emergency department . Methods We conducted a double-blind , r and omized controlled trial of children 6 months to 6 years presenting to the pediatric emergency department with a complaint of diarrhea . Patients were r and omized to receive either placebo or LGG powder twice daily for 5 days . With each dose , parents recorded the stool history in a home diary and were followed up daily by a blinded research er . Groups were compared in terms of time to normal stool and number of diarrheal stools . Results Of 155 patients enrolled , 129 completed the study : 63 in the LGG group and 66 in the placebo group . There was no significant difference in the median ( interquartile range ) time to normal stool ( LGG : 60 hours [ 37–111 ] vs placebo : 74 hours [ 43–120 ] ; P = 0.37 ) or the number of diarrheal stools ( LGG : 5.0 [ 1–10 ] vs placebo : 6.5 [ 2–14 ] ; P = 0.19 ) . Among children who presented with more than 2 days of diarrhea , the LGG group returned to normal stool earlier ( LGG : 51 hours [ 32–78 ] vs placebo : 74 hours [ 45–120 ] ; P = 0.02 ) , had fewer episodes of diarrheal stools ( LGG : 3.5 [ 1.0–7.5 ] vs placebo : 7 [ 3.0–16.3 ] ; P = 0.02 ) , and were 2.2 times more likely to return to normal stool ( 95 % confidence interval , 1.3–3.9 ; P = 0.01 ) compared with children in the placebo group . Conclusions Lactobacillus GG may reduce the duration of acute diarrheal illness among children presenting with more than 2 days of symptoms Background : Oral probiotic bacteriotherapy with Lactobacillus rhamnosus has given promising results in small children with food allergy . We studied the effects of similar therapy in teenagers and young adults , who were allergic to birch pollen and apple food and had intermittent symptoms of atopic allergy and /or mild asthma Background / Objectives : Live-attenuated influenza vaccine ( LAIV ) protects against influenza by mucosal activation of the immune system . Studies in animals and adults have demonstrated that probiotics improve the immune response to mucosally delivered vaccines . We hypothesized that Lactobacillus GG ( LGG ) would function as an immune adjuvant to increase rates of seroconversion after LAIV administration . Subjects/ Methods : We conducted a r and omized double-blind placebo-controlled pilot study to determine whether LGG improved rates of seroconversion after administration of LAIV . We studied 42 healthy adults during the 2007–2008 influenza season . All subjects received LAIV and then were r and omized to LGG or placebo , twice daily for 28 days . Hemagglutinin inhibition titers were assessed at baseline , at day 28 and at day 56 to determine the rates of seroconversion . Subjects were assessed for adverse events throughout the study period . Results : A total of 39 subjects completed the per- protocol analysis . Both LGG and LAIV were well tolerated . Protection rates against the vaccine H1N1 and B strains were suboptimal in subjects receiving LGG and placebo . For the H3N2 strain , 84 % receiving LGG vs 55 % receiving placebo had a protective titer 28 days after vaccination ( odds of having a protective titer was 1.84 95 % confidence interval 1.04–3.22 , P=0.048 ) . Conclusion : Lactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity . Future studies of probiotics as immune adjuvants might need to specifically consider examining vaccine-naïve or sero-negative subjects , target mucosal immune responses or focus on groups known to have poor response to influenza vaccines BACKGROUND Probiotics have a possible role in the treatment of pediatric acute gastroenteritis . We report the effect of the probiotic Lactobacillus rhamnosus GG ( LGG ) on intestinal function , immune response , and clinical outcomes in Indian children with cryptosporidial or rotavirus diarrhea . METHODS Children with gastroenteritis aged 6 months to 5 years , testing positive for either rotavirus or Cryptosporidium species in stool ( coinfections were excluded ) , were r and omized to LGG ( ATCC 53103 ) or placebo , once daily for 4 weeks . Baseline demographic and clinical details were obtained . Sera were tested for immunoglobulin G ( IgG ) and immunoglobulin A ( IgA ) antibodies to Cryptosporidium and rotavirus , and the lactulose to mannitol ratio for intestinal permeability was determined at baseline and at the end of follow-up . RESULTS Of the 124 children enrolled , 82 and 42 had rotavirus and cryptosporidial diarrhea , respectively . Median diarrheal duration was 4 days ; one-third of the children had severe diarrhea . Baseline and clinical parameters were comparable between children receiving LGG and placebo . At the end of follow-up , fewer children with rotavirus diarrhea on LGG had repeated diarrheal episodes ( 25 % vs 46 % ; P = .048 ) and impaired intestinal function ( 48 % vs 72 % ; P = .027 ) . Significant increase in IgG levels postintervention ( 456 vs 2215 EU ; P = .003 ) was observed in children with rotavirus diarrhea receiving LGG . Among children with cryptosporidial diarrhea , those receiving LGG showed significant improvement in intestinal permeability . CONCLUSIONS LGG has a positive immunomodulatory effect and may be useful in decreasing repeated episodes of rotavirus diarrhea . Improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis emphasizes the role of probiotics in treating intestinal impairment after infection . CLINICAL TRIALS REGISTRATION CTRI/2010/091/000339 Provision of probiotics has been limited postburn by question able potential for bacterial translocation and risk of infection in an immune-compromised population . The purpose of this study was to evaluate the safety of probiotic administration in acutely burned , pediatric patients . Subjects were r and omized to receive probiotic ( n = 10 ) vs placebo ( n = 10 ) twice daily . The investigational product was initiated within 10 days of burn , and daily supplementation continued until wound closure . Nursing staff was provided education regarding optimal procedures to minimize potential for study product cross contamination . Clinical outcomes ( infection , antibiotic , antifungal , and operative days , tolerance , and mortality ) were recorded . Length of stay was modified for burn size . Student ’s t-test , & khgr;2 test , and nonparametric Wilcoxon ’s rank-sum test were used for comparative analysis . No differences were noted ( probiotic ; placebo ) for age ( 7.1 ± 2.2 ; 6.9 ± 1.7 ) , burn size ( 38.0 ± 5.9 ; 45.5 ± 4.45 ) , full thickness ( 24.6 ± 5.6 ; 32.1 ± 5.4 ) , postburn day admit ( 0.8 ± 0.4 ; 1.1 ± 0.4 ) , or inhalation injury ( 10 % ; 20 % ) . Infection days , antibiotic use , constipation , and emesis were similar between groups . Trends toward increased antifungal and laxative use as well as diarrhea incidence were evident in the controls ( P < .30 ) . Flatulence was statistically higher with probiotics . The control group trended toward higher requirement for excision/graft procedure . Medical length of stay was not significantly different between groups ; however , time required to complete wound healing was shortened with probiotics . This study documents safety and provides preliminary efficacy data relative to probiotic supplementation postburn College students are susceptible to upper respiratory infections ( URI ) due to inadequate sleep , stress and close living quarters . Certain probiotic strains modulate immune function and may improve health-related quality of life ( HRQL ) during URI . The present study recruited apparently healthy college students and assessed the effect of probiotics on HRQL outcomes ( i.e. self-reported duration , symptom severity and functional impairment of URI ) in those who developed URI . Missed school and work days due to URI were also considered . Subjects ( n 231 ) were apparently healthy college students living on campus in residence halls at the Framingham State University ( Framingham , MA , USA ) , and were r and omised to receive placebo ( n 117 ) or probiotic-containing powder ( daily dose of minimum 1 billion colony-forming units of each Lactobacillus rhamnosus LGG ® ( LGG ® ) and Bifidobacterium animalis ssp . lactis BB-12 ® ( BB-12 ® ) ; n 114 ) for 12 weeks . Subjects completed The Wisconsin Upper Respiratory Symptom Survey-21 to assess HRQL during URI . The final analyses included 198 subjects ( placebo , n 97 and probiotics , n 101 ) . The median duration of URI was significantly shorter by 2 d and median severity score was significantly lower by 34 % with probiotics v. placebo ( P,0·001 ) , indicating a higher HRQL during URI . Number of missed work days was not different between groups ( P=0·429 ) ; however , the probiotics group missed significantly fewer school days ( mean difference = 0·2 d ) compared to the placebo group ( P=0·002 ) . LGG ® and BB-12 ® may be beneficial among college students with URI for mitigating decrements in HRQL . More research is warranted regarding mechanisms of action associated with these findings and the cost-benefit of prophylactic supplementation ABSTRACT Probiotics are believed to be beneficial in maintaining a healthy gut microbiota whereas antibiotics are known to induce dysbiosis . This study aim ed to examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 ( SB ) , the antibiotic Amoxicillin-Clavulanate ( AC ) and the combination on the microbiota and symptoms of healthy humans . Healthy subjects were r and omized to one of 4 study groups : SB for 14 days , AC for 7 days , SB plus AC , Control ( no treatment ) . Participants gave stool sample s and completed gastro-intestinal symptom question naires . Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing ( bTEFAP ) . Only one subject withdrew prematurely due to adverse events . Subjects treated by S boulardii + AC had fewer adverse events and tolerated the study regimen better than those receiving the AC alone . Control subjects had a stable microbiota throughout the study period . Significant microbiota changes were noted in the AC alone group during antibiotic treatment . AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia , Parabacteroides , and Enterobacter . Microbiota alterations reverted toward baseline , but were not yet completely restored 2 weeks after antibiotherapy . No significant shifts in bacterial genera were noted in the SB alone group . Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhea scores . Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera . S. boulardii treatment can mitigate some antibiotic-induced microbiota changes ( dysbiosis ) and can also reduce antibiotic-associated diarrhea BACKGROUND Diarrhea is a common problem in critical illness . The aim of this study was to investigate the effect of probiotic treatment with Lactobacillus rhamnosus GG on established diarrhea in critically ill patients . METHODS This prospect i ve r and omized blinded trial in the adult intensive care unit of a large tertiary referral teaching hospital compared probiotic treatment with placebo . Thirty-six consecutive critically ill enterally fed adults with diarrhea were r and omized to receive 2 capsules per day for 7 days of either Lactobacillus GG in an inulin base ( Culturelle ) or inulin alone ( placebo ) . Diarrhea was defined as ≥3 unformed stools or > 200 mL stool volume within 24 hours . Prospect ively defined primary end point was duration of diarrhea , and secondary end point was mean number of loose stools per day during the 14 days from the first capsule . Results by intention-to-treat analysis : No significant difference was observed for any end point . There was a trend toward more diarrhea in the probiotic treatment group . Mean ( st and ard deviation ) duration of diarrhea was 3.83 ( 2.39 ) days for the probiotic group and 2.56 ( 1.85 ) days for the placebo group ( P = .096 ) . Mean number of loose stools per day during the 14 days from the first capsule was 1.58 ( 0.88 ) in the probiotic group and 1.10 ( 0.79 ) in the placebo group ( P = .150 ) . CONCLUSIONS This study does not support the use of Lactobacillus GG as a treatment for established diarrhea in enterally fed critically ill patients Objective : To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by C and ida species , of late-onset sepsis and neurological outcome in preterm newborns . Study Design : A prospect i ve study was conducted in 249 preterms who were subdivided into three groups : one group ( n=83 ) was supplemented with Lactobacillus ( L. ) reuteri , one group with L. rhamnosus ( n=83 ) and the other with no supplementation ( n=83 ) . The fungal colonization in the gastrointestinal tract , the late onset of sepsis and clinical parameters were recorded . A neurological structured assessment was further performed at 1 year of age . Result : C and ida stool colonization was significantly higher ( P<0.01 ) in the control group than in the groups treated with probiotics . The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups . Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group . Conclusion : The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by C and ida , in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms BACKGROUND An important issue in sublingual immunotherapy ( SLIT ) is how to improve efficacy . OBJECTIVE To compare the clinical and immunologic efficacy of SLIT given alone and , to enhance clinical efficacy , given with probiotic or vitamin D supplementation . METHODS One hundred children , ages 5 - 12 years , sensitive to grass pollen , with allergic rhinitis participated in a 5-month prospect i ve , r and omized , double-blind , placebo-controlled trial . Children received 5-grass SLIT 300 IR tablets with either vitamin D 1000 IU daily supplementation , probiotic , or placebo . The control group included children with allergy who did not qualify for immunotherapy . Primary end points included a symptom-medication score , lung function , and exhaled nitric oxide concentration . The secondary end point was the immunologic efficacy measured by the following : CD4(+)CD25(+)Foxp3(+ ) ( forkhead box P3 ) cells , Toll-like receptor ( TLR ) 4 , interleukin ( IL ) 1 , IL-6 , tumor necrosis factor , IL-10 , and transforming growth factor β-1 levels in cell culture supernatants . RESULTS Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+ ) in children who received SLIT in all the groups were observed compared with control group . In the SLIT-probiotic group , between-group analysis showed significantly higher CD4(+)CD25(+)Foxp3(+ ) induction compared with the SLIT group and higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group ( Fig. 1 ) . An increase in CD4(+)CD25(+)Foxp3(+ ) induction , reduction in TLR-positive cells recruitment and an increase in transforming growth factor β-1 production were independently associated with a better clinical effect of SLIT in children . CONCLUSIONS We demonstrated the clinical and immunologic effect of probiotic and vitamin D supplementation on SLIT . Probiotic supplementation showed better clinical and immunologic response in children with allergic rhinitis In this r and omized controlled trial , we examined the effect of early LGG infant supplementation in decreasing the risk of childhood eczema . OBJECTIVES : To determine if probiotic administration during the first 6 months of life decreases childhood asthma and eczema . METHODS : We conducted a r and omized , double-blind controlled trial of Lactobacillus rhamnosus GG ( LGG ) supplementation on the cumulative incidence of eczema ( primary end point ) and asthma and rhinitis ( secondary end points ) in high-risk infants . For the first 6 months of life , intervention infants ( n = 92 ) received a daily dose of 10 billion colony-forming units of LGG and 225 mg of inulin ( Amerifit Br and s , Cromwell , CT ) , and control infants ( n = 92 ) received 325 mg of inulin alone . We used survival analysis methods to estimate disease incidences in the presence or absence of LGG and to estimate the efficacy of LGG in delaying or preventing these diseases . RESULTS : Infants were accrued over a 6-year period ( median follow-up : 4.6 years ; 95 % retention rate at 2 years ) . At 2 years of age , the estimated cumulative incidence of eczema was 30.9 % ( 95 % confidence interval [ CI ] , 21.4%–40.4 % ) in the control arm and 28.7 % ( 95 % CI , 19.4%–38.0 % ) in the LGG arm , for a hazard ratio of 0.95 ( 95 % CI , 0.59–1.53 ) ( log-rank P = .83 ) . At 5 years of age , the cumulative incidence of asthma was 17.4 % ( 95 % CI , 7.6%–27.1 % ) in the control arm and 9.7 % ( 95 % CI , 2.7%–16.6 % ) in the LGG arm , for a hazard ratio of 0.88 ( 95 % CI , 0.41–1.87 ) ( log-rank P = .25 ) . CONCLUSIONS : For high-risk infants , early LGG supplementation for the first 6 months of life does not appear to prevent the development of eczema or asthma at 2 years of age RATIONALE Enteral administration of probiotics may modify the gastrointestinal environment in a manner that preferentially favors the growth of minimally virulent species . It is unknown whether probiotic modification of the upper aerodigestive flora can reduce nosocomial infections . OBJECTIVES To determine whether oropharyngeal and gastric administration of Lactobacillus rhamnosus GG can reduce the incidence of ventilator-associated pneumonia ( VAP ) . METHODS We performed a prospect i ve , r and omized , double-blind , placebo-controlled trial of 146 mechanically ventilated patients at high risk of developing VAP . Patients were r and omly assigned to receive enteral probiotics ( n = 68 ) or an inert inulin-based placebo ( n = 70 ) twice a day in addition to routine care . MEASUREMENTS AND MAIN RESULTS Patients treated with Lactobacillus were significantly less likely to develop microbiologically confirmed VAP compared with patients treated with placebo ( 40.0 vs. 19.1 % ; P = 0.007 ) . Although patients treated with probiotics had significantly less Clostridium difficile-associated diarrhea than patients treated with placebo ( 18.6 vs. 5.8 % ; P = 0.02 ) , the duration of diarrhea per episode was not different between groups ( 13.2 ± 7.4 vs. 9.8 ± 4.9 d ; P = 0.39 ) . Patients treated with probiotics had fewer days of antibiotics prescribed for VAP ( 8.6 ± 10.3 vs. 5.6 ± 7.8 d ; P = 0.05 ) and for C. difficile-associated diarrhea ( 2.1 ± 4.8 SD d vs. 0.5 ± 2.3 d ; P = 0.02 ) . No adverse events related to probiotic administration were identified . CONCLUSIONS These pilot data suggest that L. rhamnosus GG is safe and efficacious in preventing VAP in a select , high-risk ICU population . Clinical trial registered with www . clinical trials.gov ( NCT00613795 ) BACKGROUND & AIMS To examine whether probiotics would reduce the occurrence or duration of acute otitis media ( AOM ) , or the nasopharyngeal carriage of otitis pathogens in otitis-prone children . METHODS During this double-blind , placebo-controlled , r and omised , 24-week intervention , 309 otitis-prone children ( 10 months-6 years ) consumed either one probiotic capsule ( Lactobacillus rhamnosus GG and LC705 , Bifidobacterium breve 99 and Propionibacterium freudenreichii JS ) ( n=155 ) or placebo ( n=154 ) daily . Clinical examinations were carried out and nasopharyngeal sample s taken three times . Parents recorded the symptoms of upper respiratory infection ( URI ) in a diary . RESULTS Probiotic treatment did not reduce the occurrence ( probiotic vs. placebo : 72 % vs. 65 % , OR=1.48 , 95 % CI 0.87 - 2.52 , p = n.s . ) or the recurrence ( three ) of AOM episodes ( 18 % vs. 17 % , OR=1.04 , 95 % CI 0.55 - 1.96 , p = n.s . ) . The median duration of AOM episodes was 5.6 ( IQR 3.5 - 9.4 ) vs. 6.0 ( IQR 4.0 - 10.5 ) days , respectively ( p= n.s . ) . There was a tendency showing a reduction in the occurrence of recurrent ( 4 to 6 ) respiratory infections in the probiotic group ( OR for 4 URIs : 0.56 , 95%CI 0.31 - 0.99 , p=0.046 ; OR for 6 URIs : 0.59 , 95 % CI 0.34 to 1.03 , p = n.s . ) . Probiotics did not affect the carriage of Streptococcus pneumoniae or Haemophilus influenzae , but increased the prevalence of Moraxella catarrhalis ( OR=1.79 , 95 % CI 1.06 - 3.00 , p=0.028 ) . CONCLUSIONS Probiotics did not prevent the occurrence of AOM or the nasopharyngeal carriage of otitis pathogens in otitis-prone children . A tendency showing a reduction in recurrent respiratory infections must be confirmed in further studies Background and aims : Experimental studies have shown that luminal bacteria may be involved in Crohn 's disease . Probiotics are a possible alternative to antibiotics . The aim of this r and omised placebo controlled study was to determine if Lactobacillus GG , given by mouth for one year , could prevent Crohn 's recurrent lesions after surgery or to reduce their severity . Methods : Patients operated on for Crohn 's disease in whom all of the diseased gut had been removed were r and omly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year . Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms . Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system . Results : Eight of 45 patients were excluded from the trial ( three for non-compliance and five for protocol violations ) . Clinical recurrence was ascertained in three ( 16.6 % ) patients who received Lactobacillus and in two ( 10.5 % ) who received placebo . Nine of 15 patients in clinical remission on Lactobacillus ( 60 % ) had endoscopic recurrence compared with six of 17 ( 35.3 % ) on placebo ( p=0.297 ) . There were no significant differences in the severity of the lesions between the two groups . Conclusions : Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions Abstract Objective : To examine whether long term consumption of a probiotic milk could reduce gastrointestinal and respiratory infections in children in day care centres . Design : R and omised , double blind , placebo controlled study over seven months . Setting : 18 day care centres in Helsinki , Finl and . Participants : 571 healthy children aged 1 - 6 years : 282 ( mean ( SD ) age 4.6 ( 1.5 ) years ) in the intervention group and 289 ( mean ( SD ) age 4.4 ( 1.5 ) years ) in the control group . Intervention : Milk with or without Lactobacillus GG . Average daily consumption of milk in both groups was 260 ml . Main outcome measures : Number of days with respiratory and gastrointestinal symptoms , absences from day care because of illness , respiratory tract infections diagnosed by a doctor , and course of antibiotics . Results : Children in the Lactobacillus group had fewer days of absence from day care because of illness ( 4.9 ( 95 % confidence interval 4.4 to 5.5 ) v 5.8 ( 5.3 to 6.4 ) days , 16 % difference , P=0.03 ; age adjusted 5.1 ( 4.6 to 5.6 ) v 5.7 ( 5.2 to 6.3 ) days , 11 % difference , P=0.09 ) . There was also a relative reduction of 17 % in the number of children suffering from respiratory infections with complications and lower respiratory tract infections ( unadjusted absolute % reduction −8.6 ( −17.2 to −0.1 ) , P=0.05 ; age adjusted odds ratio 0.75 ( 0.52 to 1.09 ) , P=0.13 ) and a 19 % relative reduction in antibiotic treatments for respiratory infection ( unadjusted absolute % reduction −9.6 ( −18.2 to −1.0 ) , P=0.03 ; adjusted odds ratio 0.72 ( 0.50 to 1.03 ) , P=0.08 ) in the Lactobacillus group . Conclusions : Lactobacillus GG may reduce respiratory infections and their severity among children in day care . The effects of the probiotic Lactobacillus GG were modest but consistently in the same direction . What is already known on this topic Children attending day care centres are at high risk of respiratory and gastrointestinal infection The successful prevention of respiratory infections could be extremely useful for families and for society in general Short term use of probiotic bacteria has been shown to reduce the severity of rotavirus diarrhoea and the incidence of diarrhoea associated with the use of antibiotics What this study adds In a double blind , r and omised , long term study milk containing Lactobacillus GG slightly reduced the incidence of respiratory infections and antibiotic treatment in Background Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn 's disease and ulcerative colitis . Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission . The aim of this r and omized , placebo-controlled trial was to determine the effect of oral Lactobacillus GG ( L. GG ) to induce or maintain medically induced remission . Methods Eleven patients with moderate to active Crohn 's disease were enrolled in this trial to receive either L. GG ( 2 × 109 CFU/day ) or placebo for six months . All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated . The primary end point was sustained remission , defined as freedom from relapse at the 6 months follow-up visit . Relapse was defined as an increase in CDAI of > 100 points . Results 5/11 patients finished the study , with 2 patients in each group in sustained remission . The median time to relapse was 16 ± 4 weeks in the L. GG group and 12 ± 4.3 weeks in the placebo group ( p = 0.5 ) . Conclusion In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD Abstract The primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori . The study was multicenter , prospect i ve , r and omized , placebo controlled , and double-blind . The subjects first filled out a specially design ed question naire to assess the severity of the 10 symptoms , which can be related to eradication therapy to be monitored during the trial . Each subject then received 28 capsules of probiotic preparation or matching placebo capsules , which they were supposed to take over the following 14 days , twice a day , at least 2 hours prior to or after the antibiotic therapy administration . A total of 804 patients were enrolled in the trial , of which 650 ( 80.85 % ) were included in the analysis . The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm ( 87.38 % vs 72.55 % ; P < 0.001 ) . Additionally , presence and intensity of epigastric pain , bloating , flatulence , taste disturbance , loss of appetite , nausea , vomiting , heartburn , rash , and diarrhea were monitored over the study period . At 15 days post inclusion , probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms . Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group , 0.76 vs 0.55 ( P < 0.001).Adding probiotics to the st and ard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease BACKGROUND & AIMS To examine the effect of supplementation with probiotics on respiratory and gastrointestinal illness in healthy active men and women . METHODS A r and omised double-blind placebo-controlled trial was conducted . Four hundred and sixty five participants ( 241 males ; age 35 ± 12 y ( mean ± SD ) and 224 females ; age 36 ± 12 y ) were assigned to one of three groups : Group 1 - Bifidobacterium animalis subsp . lactis Bl-04 ( Bl-04 ) 2.0 × 10(9)colony forming units per day , CFU per day , Group 2 - Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp . lactis Bi-07 ( NCFM & Bi-07 ) 5 × 10(9 ) CFU each per day ) or Group 3 - placebo mixed in a drink . RESULTS The risk of an upper respiratory illness episode was significantly lower in the Bl-04 group ( hazard ratio 0.73 ; 95 % confidence interval 0.55 - 0.95 ; P = 0.022 ) compared to placebo . There was no significant difference in illness risk between the NCFM & Bi-07 group ( hazard ratio 0.81 ; 0.62 - 1.08 ; P = 0.15 ) and the placebo group . There was a 0.7 and 0.9 month delay in the median time to an illness episode in the Bl-04 and NCFM & Bi-07 groups respectively compared to placebo ( placebo 2.5 months ; Bl-04 3.2 months ; NCFM & Bi-07 3.4 months ) . There were insufficient GI illness episodes for analysis . The NCFM & Bi-07 group but not the Bl-04 group undertook significantly more physical activity ( 8.5 % ; 6.7%-10 % ; P < 0.003 ) than the placebo group . CONCLUSION The probiotic Bl-04 appears to be a useful nutritional supplement in reducing the risk of URTI in healthy physically-active adults . TRIAL REGISTRATION Australia New Zeal and Clinical Trials Registry : Number ACTRN12611000130965 Acidogenicity and the levels of mutans streptococci ( MS ) in dental plaque after the use of Lactobacillus rhamnosus GG ( LGG ) and Lactobacillus reuteri were determined . The study had a r and omised , double-blind , crossover design . Thirteen volunteers used tablets containing LGG or a combination of L. reuteri SD2112 and PTA 5289 for 2 weeks . At baseline and at the end of each tablet period , all available supragingival plaque was collected . Lactic acid production was determined from a fixed volume ( 8 μl ) of fresh plaque and the rest of the plaque was used for culturing MS and lactobacilli . The retention of probiotics to the plaque was assessed using PCR techniques . No probiotic-induced changes were found in the acidogenicity of plaque . Also , MS counts remained at the original level . The number of subjects with lactobacilli in plaque increased in the L. reuteri group ( p = 0.011 ) but not in the LGG group . PCR analysis of plaque revealed the presence of LGG in four and L. reuteri in six subjects after the use of the probiotic . The use of the lactobacilli did not affect the acidogenicity or MS levels of plaque . Short-term consumption of LGG and L. reuteri appeared not to influence the acidogenicity of plaque BACKGROUND & AIMS To establish whether probiotic supplemented dietary counselling influences maternal anthropometric measurements during and after pregnancy . METHODS At the first trimester of pregnancy 256 women were r and omly assigned to receive nutrition counselling to modify dietary intake according to current recommendations or as controls ; dietary intervention groups were further r and omized to receive probiotics Lactobacillus rhamnosus GG ( ATCC 53103 ) and Bifidobacterium lactis ( diet/probiotics ) or placebo ( diet/placebo ) capsules in a double-blind manner , whilst the controls received placebo ( control/placebo ) . The intervention lasted until the end of exclusive breastfeeding for up to six months . RESULTS The risk of central adiposity defined as waist circumference 80 cm or more was lowered in women in the diet/probiotics group compared with the control/placebo group ( OR 0.30 , 95%CI 0.11 - 0.85 , p = 0.023 adjusted for baseline BMI ) , whilst the diet/placebo group did not differ from the controls ( OR 1.00 , 95 % CI 0.38 - 2.68 , p = 0.994 ) at 6 months postpartum . The number needed to treat ( NNT ) with diet/probiotics to prevent one woman from developing a waist circumference of 80 cm or more was 4 . Healthy eating pattern at 12 months postpartum ( p = 0.001 ) and BMI prior to pregnancy ( p < 0.001 ) were strong determinants of BMI at 12 months postpartum when adjusted for dietary intervention and exercise . CONCLUSION The impact of probiotics-supplemented dietary counselling on central adiposity , may offer a novel means for the prevention and management of obesity . This trial was registered at clinical trials.gov as NCT 00167700 , section 3 OBJECTIVES To determine the benefits of Lactobacillus rhamnosus GG ( LGG ) in an extensively hydrolyzed casein formula ( EHCF ) in improving hematochezia and fecal calprotectin over EHCF alone . STUDY DESIGN Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group . We also compared fecal calprotectin and hematochezia on 26 formula-fed infants r and omly assigned to EHCF with LGG ( Nutramigen LGG ) ( EHCF + LGG ) or without ( Nutramigen ) ( EHCF - LGG ) and on 4 breastfed infants whose mothers eliminated dairy . RESULTS Fecal calprotectin in those with hematochezia was significantly higher than in comparisons ( mean + /- SD 325.89 + /- 152.31 vs 131.97 + /- 37.98 microg/g stool , t = 6.79 , P < .0001 ) . At 4 weeks , fecal calprotectin decreased to 50 % of baseline but was still significantly higher than in comparisons ( 157.5 + /- 149.13 vs 93.72 + /- 36.65 microg/g , P = .03 ) . Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF - LGG ( -214.5 + /- 107.93 vs -112.7 + /- 105.27 microg/g , t = 2.43 , P = .02 ) . At 4 weeks , none of the EHCF + LGG had blood in stools , and 5/14 on EHCF - LGG did ( P = .002 ) . CONCLUSION Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis . EHCF + LGG result ed in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone Background & objectives : R and omized controlled trials in developed countries have reported benefits of Lactobacillus GG ( LGG ) in the treatment of acute watery diarrhoea , but there is paucity of such data from India . The study was aim ed to evaluate the efficacy and safety of Lactobacillus GG in the treatment of acute diarrhoea in children from a semi-urban city in north India . Methods : In this open labelled , r and omized controlled trial 200 children with acute watery diarrhoea , aged between 6 months to 5 years visiting outpatient department and emergency room of a teaching hospital in north India were enrolled . The children were r and omized into receiving either Lactobacillus GG in dose of 10 billion cfu/day for five days or no probiotic medication in addition to st and ard WHO management of diarrhoea . Primary outcomes were duration of diarrhoea and time to change in consistency of stools . Results : Median ( inter quartile range ) duration of diarrhoea was significantly shorter in children in LGG group [ 60 ( 54 - 72 ) h vs. 78 ( 72 - 90 ) h ; P<0.001 ] . Also , there was faster improvement in stool consistency in children receiving Lactobacillus GG than control group [ 36 ( 30 - 36 ) h vs. 42 ( 36 - 48 ) h ; P<0.001 ] . There was significant reduction in average number of stools per day in LGG group ( P<0.001 ) compared to the control group . These benefits were seen irrespective of rotavirus positivity in stool tests . Interpretation & conclusions : Our results showed that the use of Lactobacillus GG in children with acute diarrhoea result ed in shorter duration and faster improvement in stool consistency as compared to the control group OBJECTIVES To assess the efficacy of Lactobacillus GG in preventing antibiotic-associated diarrhea ( AAD ) in adults and , secondarily , to assess the effect of coadministered Lactobacillus GG on the number of tests performed to determine the cause of diarrhea . PATIENTS AND METHODS In this prospect i ve , r and omized , double-blind , placebo-controlled trial conducted from July 1998 to October 1999 , 302 hospitalized patients receiving antibiotics were r and omized to receive Lactobacillus GG , 20 x 10(9 ) CFU/d , or placebo for 14 days . Subjects recorded the number of stools and their consistency daily for 21 days . The primary outcome was the proportion of patients who developed diarrhea in the first 21 days after enrollment . Weekly telephone follow-up was also performed . Results were analyzed in an intention-to-treat fashion . RESULTS Diarrhea developed in 39 ( 29.3 % ) of 133 patients r and omized to receive Lactobacillus GG and in 40 ( 29.9 % ) of 134 patients r and omized to receive placebo ( P=.93 ) . No additional difference in the rate of occurrence of diarrhea was found between treatment and placebo patients in a subgroup analysis of those treated with beta-lactam vs non-beta-lactam antibiotics . Too few patients had stool cultures , additional laboratory tests for diarrhea , or a positive diagnosis of Clostridium difficile infection to assess between-group differences . CONCLUSION Lactobacillus GG in a dose of 20 x 10(9 ) CFU/d did not reduce the rate of occurrence of diarrhea in this sample of 267 adult patients taking antibiotics initially administered in the hospital setting Background Simple and safe strategies for the prevention of viral respiratory tract infections ( RTIs ) are needed . Objective We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants . Methods In this r and omized , double-blind , placebo-controlled trial ( Clinical Trials.gov no. NCT00167700 ) , 94 preterm infants ( gestational age , ≥32 + 0 and ≤36 + 6 weeks ; birth weight , > 1500 g ) treated at Turku University Hospital , Turku , Finl and , were allocated to receive oral prebiotics ( galacto-oligosaccharide and polydextrose mixture , 1:1 ) , a probiotic ( Lactobacillus rhamnosus GG , ATCC 53103 ) , or placebo ( microcrystalline cellulose ) between days 3 and 60 of life . The primary outcome was the incidence of clinical ly defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing . Secondary outcomes were the severity and duration of RTIs . Results A significantly lower incidence of RTIs was detected in infants receiving prebiotics ( rate ratio [ RR ] , 0.24 ; 95 % CI , 0.12 - 0.49 ; P < .001 ) or probiotics ( RR , 0.50 ; 95 % CI , 0.28 - 0.90 ; P = .022 ) compared with those receiving placebo . Also , the incidence of rhinovirus-induced episodes , which comprised 80 % of all RTI episodes , was found to be significantly lower in the prebiotic ( RR , 0.31 ; 95 % CI , 0.14 - 0.66 ; P = .003 ) and probiotic ( RR , 0.49 ; 95 % CI , 0.24 - 1.00 ; P = .051 ) groups compared with the placebo group . No differences emerged among the study groups in rhinovirus RNA load during infections , duration of rhinovirus RNA shedding , duration or severity of rhinovirus infections , or occurrence of rhinovirus RNA in asymptomatic infants . Conclusions Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections A r and omised , double-blind , placebo-controlled study was conducted to determine whether probiotics might be effective in reducing the risk of infections in infancy . Infants requiring formula before the age of 2 months were recruited from community well-baby clinics . Infant formula supplemented with the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 or placebo was administered daily until the age of 12 months . Incidence of early infections ( before the age of 7 months ) and incidence of recurrent ( three or more ) infections during the first year of life were recorded as the main outcome measures of the study . During the first 7 months of life , seven out of thirty-two ( 22 % ) infants receiving probiotics and twenty out of forty ( 50 % ) infants receiving placebo experienced acute otitis media ( risk ratio ( RR ) 0.44 ( 95 % CI 0.21 , 0.90 ) ; P = 0.014 ) and antibiotics were prescribed for ten out of thirty-two ( 31 % ) infants receiving probiotics and twenty-four out of forty ( 60 % ) infants receiving placebo ( RR 0.52 ( 95 % CI 0.29 , 0.92 ) ; P = 0.015 ) . During the first year of life , nine out of thirty-two ( 28 % ) infants receiving probiotics and twenty-two out of forty ( 55 % ) infants receiving placebo encountered recurrent respiratory infections ( RR 0.51 ( 95 % CI 0.27 , 0.95 ) ; P = 0.022 ) . These data suggest that probiotics may offer a safe means of reducing the risk of early acute otitis media and antibiotic use and the risk of recurrent respiratory infections during the first year of life . Further clinical trials are warranted Objectives The aim was to evaluate the effects of orally administered Lactobacillus rhamnosus GG ( LGG ) and Bifidobacterium animalis subsp . lactis BB-12 ( BB-12 ) on the number of salivary mutans streptococci ( MS ) , amount of plaque , gingival inflammation and the oral microbiota in healthy young adults . Material s and methods The study was a r and omised , controlled , double-blind trial . Healthy volunteers used lozenges containing a combination of LGG and BB-12 ( test group , n = 29 ) or lozenges without added probiotics ( control group , n = 31 ) for 4 weeks . At baseline and at the end of the test period , the plaque index ( PI ) and gingival index ( GI ) were determined , and stimulated saliva was collected . The microbial composition of saliva was assessed using human oral microbe identification microarray ( n = 30 ) . MS and lactobacilli ( LB ) were plate cultured . Results The probiotic lozenge decreased both PI and GI ( p < 0.05 ) while no changes were observed in the control group . However , no probiotic-induced changes were found in the microbial compositions of saliva in either group . Conclusions The probiotic lozenge improved the periodontal status without affecting the oral microbiota . Clinical relevance Short-term consumption of LGG and BB-12 decreased the amount of plaque which was associated with a clinical impact : a decrease in gingival inflammation Background Perinatal probiotics supplementation has been shown to be effective in the primary prevention of atopic dermatitis ( AD ) in early childhood , although the long term effects of probiotics on AD and other allergic diseases is less certain . We have previously reported a significant reduction in the cumulative incidence of AD at 2 years after maternal probiotic supplementation . In this study we present the effects of perinatal probiotics given to women from a general population on allergy related diseases in their offspring at 6 years . Methods Four hundred and fifteen pregnant women were r and omised to receive probiotic or placebo milk in a double-blinded trial from 36 week gestation until 3 months postpartum . Probiotic milk contained Lactobacillus rhamnosos GG , L. acidophilus La-5 and Bifidobacterium animalis subsp . lactis Bb-12 . At 6 years , children were re-assessed for AD , atopic sensitisation , asthma and allergic rhinoconjunctivitis ( ARC ) . Results At 6 years , 81 and 82 children were assessed for AD in the probiotic and placebo groups , respectively . In a multiple imputation analysis , there was as trend towards a lower cumulative incidence of AD in the probiotic group compared to the placebo group ( OR 0.64 , 95 % CI 0.39 - 1.07 , p = 0.086 ; NNT = 10 ) . This finding was statistically significantly in the complete case analysis ( OR 0.48 , 95 % CI 0.25 - 0.92 , p = 0.027 , NNT = 6 ) . The prevalence of asthma and atopic sensitisation , and the cumulative incidence of ARC were not significantly affected by the probiotic regime at 6 years of age . Conclusions Maternal probiotic ingestion alone may be sufficient for long term reduction in the cumulative incidence of AD , but not other allergy related diseases . Trial registration Clinical Trials.gov identifier : Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response . Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children . Here we describe high-resolution culture-independent analysis of stool sample s from 6-month old infants fed daily supplements of Lactobacillus casei subsp . Rhamnosus ( LGG ) or placebo in a double-blind , r and omized Trial of Infant Probiotic Supplementation ( TIPS ) . Bacterial community composition was examined using a high-density microarray , the 16S rRNA PhyloChip , and the microbial assemblages of infants with either high or low LGG abundance were compared . Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species , and were significantly more even in their distribution of community members . Ecologically , these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens . PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy , as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species . From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable , even , and functionally redundant infant gastrointestinal community BACKGROUND Age-related changes in the physiology and intestinal function of the elderly render them more susceptible to gut-related illnesses . Probiotic dietary supplementation has been shown to enhance the health indices in the elderly . OBJECTIVE To determine the effect of three different doses [ 5 x 109 CFU/day ( high ) , 1.0 x 109 CFU/day ( medium ) and 6.5 x 107 CFU/day ( low ) ] of Bifidobacterium lactis HN019 ( DR10TM ) on the intestinal flora of elderly human subjects and the dose response effect . DESIGN R and omised , double-blind and placebo-controlled human dietary intervention study consisting of four groups of 20 elderly ( over 60 years old ) volunteers . Each volunteer consumed 250 mL per day of reconstituted skim milk ( RSM ) which either did not contain any probiotic supplement ( placebo group ) or contained B. lactis HN019 at different levels ( low , medium and high dose groups ) . The study comprised three stages : a 2-week pre-intervention ( without any supplement ) , followed by 4 weeks of test feeding ( dietary intervention ) and then a 2-week washout period . RESULTS After dietary intervention , statistically significant increases in bifidobacteria , lactobacilli and enterococci were observed . At the end of the 4-week feeding period the mean number of bifidobacteria recorded in the placebo group were 9.31 + /- 0.01 log CFU/g of faeces . In the high , medium and low dose groups the bifidobacteria levels were significantly ( p < 0.006 ) higher ( 9.88 + /- 0.1 , 9.75 + /- 0.14 and 9.74 + /- 0.11 log CFU/g of faeces , respectively ) , when compared to the respective pre-intervention levels . There were no significant differences ( p superior 0.05 ) between the responses of the different dose groups , indicating that even the lowest dose tested augmented the changes in bifidobacteria . Similar trends were observed for lactobacilli and enterococci . In contrast , the counts of enterobacteria were reduced in all the probiotic dose groups . CONCLUSION The present study showed that dietary supplementation with B. lactis HN019 significantly increased the number of resident bifidobacteria and reduced the enterobacteria counts . In addition , enterococci and lactobacilli were also increased . Based on this study and already published clinical evidence ( 4 , 5 , 8 , 9 ) we conclude that , B. lactis HN019 is a suitable probiotic for elderly human subjects and even the lowest dose ( 6.5 x 107 CFU/day ) tested is able to confer desired changes in the intestinal microflora Antibiotic use is considered among the most severe causes of disturbance to children ’s developing intestinal microbiota , and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections . Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms . However , it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children ’s microbiota . Furthermore , it is not known how long-term probiotic consumption influences the developing microbiota of children . We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children ’s antibiotic use , and antibiotic-associated gastrointestinal complaints in a double blind , r and omized placebo-controlled trial with 231 children aged 2–7 . In addition , we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children . The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children , causing an increase in the abundance of Prevotella , Lactococcus , and Ruminococcus , and a decrease in Escherichia . The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use , but not those associated with macrolide use . The treatment , however , did reduce the frequency of gastrointestinal complaints after a macrolide course . Finally , the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial , as indicated by reduced antibiotic use . Trial Registration : Clinical Trials.gov This is a r and omized , placebo-controlled study in which we examine the effect of probiotics ( BB-12 and LGG ) on child care absenteeism and infections in infants . OBJECTIVES : The risk of infections is higher in children attending child care compared with children cared for at home . This study examined the effect of a combination of probiotics on absence from child care because of respiratory and gastrointestinal infections in healthy infants aged 8 to 14 months at the time of enrollment in child care . METHODS : The ProbiComp study was a r and omized , double-blind , placebo-controlled study . A total of 290 infants were r and omly allocated to receive a placebo or a combination of Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus in a dose of 109 colony-forming units of each daily for a 6-month intervention period . Absence from child care , occurrence of infant symptoms of illness , and doctor visits were registered by the parents using daily and weekly Web-based question naires . RESULTS : Median absence from child care was 11 days ( interquartile range : 6–16 ) . Intention-to-treat analysis showed no difference between the probiotics and placebo groups ( P = .19 ) . Additionally , there was no difference in any of the secondary outcomes between groups ; the number of children with doctor-diagnosed upper or lower respiratory tract infections , the number of doctor visits , antibiotic treatments , occurrence and duration of diarrhea , and days with common cold symptoms , fever , vomiting , or caregivers ’ absence from work . CONCLUSIONS : A daily administration of a combination of B animalis subsp lactis and L rhamnosus for 6 months did not reduce the number of days absent from child care in healthy infants at the time of enrollment in child care OBJECTIVE : The incidence of nosocomial infections , predominantly gastrointestinal and respiratory , in children in developed countries is high , ranging from 5 % to 44 % . There is no effective strategy for preventing these infections . The objective of our study was to investigate the role of Lactobacillus GG ( LGG ) in preventing nosocomial gastrointestinal and respiratory tract infections at a pediatric hospital . METHODS : We conducted a r and omized , double-blind , placebo-controlled trial of 742 hospitalized children . They were r and omly allocated to receive for their hospitalization LGG at a dose of 109 colony-forming units in 100 mL of a fermented milk product ( LGG group , n = 376 ) or placebo that was the same postpasteurized fermented milk product without LGG ( placebo group , n = 366 ) . RESULTS : In the LGG group , compared with the placebo group , we found a significantly reduced risk for gastrointestinal infections ( relative risk [ RR ] : 0.40 [ 95 % confidence interval ( CI ) : 0.25–0.70 ] ; number needed to treat : 15 [ 95 % CI : 9–34 ) ] , respiratory tract infections ( RR : 0.38 [ 95 % CI : 0.18–0.85 ] ; number needed to treat : 30 [ 95 % CI : 16–159 ] ) , vomiting episodes ( RR : 0.5 [ 95 % CI : 0.3–0.9 ] ) , diarrheal episodes ( RR : 0.24 [ 95 % CI : 0.10–0.50 ] ) , episodes of gastrointestinal infections that lasted > 2 days ( RR : 0.40 [ 95 % CI : 0.25–0.70 ] ) , and episodes of respiratory tract infections that lasted > 3 days ( RR : 0.4 [ 95 % CI : 0.2–0.9 ] ) . Groups did not differ in hospitalization duration ( P = .1 ) . CONCLUSIONS : LGG administration can be recommended as a valid measure for decreasing the risk for nosocomial gastrointestinal and respiratory tract infections in pediatric facilities Background Children with cow 's milk allergy ( CMA ) have an increased risk of other allergic manifestations ( AMs ) . Objective We performed a parallel‐arm r and omized controlled trial to test whether administration of an extensively hydrolyzed casein formula ( EHCF ) containing the probiotic Lactobacillus rhamnosus GG ( LGG ) can reduce the occurrence of other AMs in children with CMA . Methods Children with IgE‐mediated CMA were r and omly allocated to the EHCF or EHCF+LGG groups and followed for 36 months . The main outcome was occurrence of at least 1 AM ( eczema , urticaria , asthma , and rhinoconjunctivitis ) . The secondary outcome was tolerance acquisition , which was defined as the negativization of a double‐blind food challenge results at 12 , 24 , and 36 months . AMs were diagnosed according to st and ardized criteria . Tolerance acquisition was evaluated every 12 months . Results A total of 220 children ( 147 boys [ 67 % ] ) with a median age of 5.0 months ( interquartile range , 3.0‐8.0 months ) were r and omized ; 110 children were placed in the EHCF group , and 110 children were placed in the EHCF+LGG group . In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was −0.23 ( 95 % CI , −0.36 to −0.10 ; P < .001 ) , and the absolute risk difference for the acquisition of cow 's milk tolerance was 0.20 ( 95 % CI , 0.05‐0.35 ; P < .01 ) at 12 months , 0.24 ( 95 % CI , 0.08‐0.41 ; P < .01 ) at 24 months , and 0.27 ( 95 % CI , 0.11‐0.43 ; P < .001 ) at 36 months . In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children . Conclusions EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE‐mediated CMA Objective : To study the preventive effect of a milk drink fermented with multistrain probiotics on antibiotic associated diarrhoea ( AAD ) . Design : Double-blind placebo controlled study . Setting : University Hospital of North Norway . Subjects and methods : Of 853 patients treated with antibiotics , 87 met the inclusion criteria , and were r and omized to ingestion of a fermented milk drink containing LGG , La-5 and Bb-12 ( n=46 ) or placebo with heat-killed bacteria ( n=41 ) , during a period of 14 days . A diary was recorded , and stool sample s were collected for microbiological analyses . Results : Sixty-three patients completed the study according to the protocol ; two patients ( 5.9 % ) in the treatment group and eight ( 27.6 % ) in the placebo group developed AAD ( P=0.035 ) . The relative risk of developing AAD was 0.21 ( 95 % confidence interval : 0.05–0.93 ) when given probiotic milk drink . Conclusion : A fermented multistrain probiotic milk drink may prevent four of five cases of AAD in adult hospitalized patients .Sponsorship : TINE BA , Oslo , Norway OBJECTIVE : Probiotic consumption effects on cold and influenza-like symptom incidence and duration were evaluated in healthy children during the winter season . METHODS : In this double-blind , placebo-controlled study , 326 eligible children ( 3–5 years of age ) were assigned r and omly to receive placebo ( N = 104 ) , Lactobacillus acidophilus NCFM ( N = 110 ) , or L acidophilus NCFM in combination with Bifidobacterium animalis subsp lactis Bi-07 ( N = 112 ) . Children were treated twice daily for 6 months . RESULTS : Relative to the placebo group , single and combination probiotics reduced fever incidence by 53.0 % ( P = .0085 ) and 72.7 % ( P = .0009 ) , coughing incidence by 41.4 % ( P = .027 ) and 62.1 % ( P = .005 ) , and rhinorrhea incidence by 28.2 % ( P = .68 ) and 58.8 % ( P = .03 ) , respectively . Fever , coughing , and rhinorrhea duration was decreased significantly , relative to placebo , by 32 % ( single strain ; P = .0023 ) and 48 % ( strain combination ; P < .001 ) . Antibiotic use incidence was reduced , relative to placebo , by 68.4 % ( single strain ; P = .0002 ) and 84.2 % ( strain combination ; P < .0001 ) . Subjects receiving probiotic products had significant reductions in days absent from group child care , by 31.8 % ( single strain ; P = .002 ) and 27.7 % ( strain combination ; P < .001 ) , compared with subjects receiving placebo treatment . CONCLUSION : Daily dietary probiotic supplementation for 6 months was a safe effective way to reduce fever , rhinorrhea , and cough incidence and duration and antibiotic prescription incidence , as well as the number of missed school days attributable to illness , for children 3 to 5 years of age OBJECTIVE To determine whether oral administration of the probiotic Lactobacillus GG under r and omized , double-blinded , placebo-controlled conditions would improve symptoms of irritable bowel syndrome ( IBS ) in children . STUDY DESIGN Fifty children fulfilling the Rome II criteria for IBS were given Lactobacillus GG or placebo for 6 weeks . Response to therapy was recorded and collected on a weekly basis using the Gastrointestinal Symptom Rating Scale ( GSRS ) . RESULTS Lactobacillus GG was not superior to placebo in relieving abdominal pain ( 40.0 % response rate in the placebo group vs 44.0 % in the Lactobacillus GG group ; P=.774 ) . There was no difference in the other gastrointestinal symptoms , except for a lower incidence of perceived abdominal distention ( P=.02 favoring Lactobacillus GG ) . CONCLUSIONS Lactobacillus GG was not superior to placebo in the treatment of abdominal pain in children with IBS but may help relieve such symptoms as perceived abdominal distention BACKGROUND Helicobacter pylori ( Hp ) eradication fails in about 10 % of patients because of the occurrence of resistance to antibiotics and side-effects . During anti H.pylori therapy , probiotics have been used to reduce the incidence of side-effects . OBJECTIVES To determine whether adding the probiotic Lactobacillus rhamhousus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effect burden . MATERIAL AND METHODS 66 subjects screening positive for H. pylori infection ( male/female : 45/21 , mean age 56,6 DS ± 16,7 year ) , 59 subjects receiving 7 days of Omeprazole 20 mg b.i.d , Amoxicillin 1000 mg b.i.d and Clarithromycin 500 mg b.i.d were r and omly assigned to Lactobacillus rhamnosus GG ( 6 x 9 ufc b.i.d ) ( n = 29 ) or placebo ( n = 30 ) . Patients completed question naires after the treatment to determine the type and 10 severity of side-effects . RESULTS Side effects occurred mainly during the eradication therapy ; none of them caused therapy discontinuation . Bloating , diarrhea , taste disturbance and epigastric discomfort were the most frequent side effects : ( 10.3 % versus 16 % , 13.8 % versus 20 % , 13.7 % versus 20 % and 13.7 % versus 20 % respectively ) . No significant differences were found between the two groups for individual symptoms . CONCLUSION In this study , probiotic supplementation did not diminish significantly the frequency of new or aggravated symptoms during H. pylori eradication & NA ; Probiotics are widely used by patients with Crohn 's disease ( CD ) in an attempt to improve their health , but few controlled studies have been done to evaluate the efficacy of these therapies . We conducted a r and omized , placebo‐controlled trial of the probiotic Lactobacillus rhamnosus strain GG ( LGG ) to see if the addition of LGG to st and ard therapy prolonged remission in children with CD . Concomitant medications allowed in the study included aminosalicylates , 6‐mercaptopurine , azathioprine , and low‐dose alternate day corticosteroids . Seventy‐five children ( age range , 5‐21 yr ) with CD in remission were r and omized to either LGG ( n = 39 ) or placebo ( n = 36 ) and followed for up to 2 years . The median time to relapse was 9.8 months in the LGG group and 11.0 months in the placebo group ( P = 0.24 ) ; 31 % ( 12/39 ) of patients in the LGG group developed a relapse compared with 6/36 ( 17 % ) of the placebo group ( P = 0.18 ) . The LGG was well tolerated , with a side effect profile comparable with placebo . This study suggests that LGG does not prolong time to relapse in children with CD when given as an adjunct to st and ard therapy OBJECTIVE To evaluate the impact of early prebiotic and probiotic intervention on preterm infants ' well-being , crying , growth , and microbiological programming . STUDY DESIGN Ninety-four preterm infants ( gestational age 32 - 36 weeks and birth weight > 1500 g ) r and omized to receive prebiotics ( mixture of galacto-oligosaccharide and polydextrose 1:1 ) , probiotics ( Lactobacillus rhamnosus GG ) , or placebo during the first 2 months of life were followed up for 1 year . Infants were categorized based on the extent of crying and irritability during the first 2 months of life , and their gut microbiota was investigated by fluorescence in situ hybridization ( n = 66 ) and quantitative polymerase chain reaction ( n = 63 ) . RESULTS A total of 27 of 94 infants ( 29 % ) infants were classified as excessive criers , significantly less frequently in the prebiotic and the probiotic groups than in the placebo group ( 19 % vs 19 % vs 47 % , respectively ; P = .02 ) . The placebo group had a higher percentage of Clostridium histolyticum group bacteria in their stools than did the probiotic group ( 13.9 % vs 8.9 % , respectively ; P = .05 ) . There were no adverse events related to either supplementation . CONCLUSIONS Early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants . This original finding may offer new therapeutic and preventive measures for this common disturbance in early life Background / Objectives : To determine whether long-term daily consumption of milk containing probiotic Lactobacillus rhamnosus GG ( GG ) decreases respiratory illness in children . Subjects/ Methods : A r and omized , double-blind , placebo-controlled trial was conducted with 523 children aged 2–6 years attending day care centers in Finl and . Subjects received either normal milk or the same milk with GG on three daily meals for 28 weeks . Daily recording of childrens ’ symptoms was done by parents . Primary outcome data from 501 subjects were available for analysis , and data from 128 subjects were analyzed as completed cases in terms of recovery of GG in fecal sample s. Results : Number of days with at least one respiratory symptom in all subjects was 5.03/month ( 95 % confidence interval ( CI ) : 4.92–5.15 ) in the GG group and 5.17/month ( 95 % CI : 5.05–5.29 ) in the placebo group incidence rate ratio ( IRR ) 0.97 ; 95 % CI : 0.94–1.00 ; P=0.098 ) . In the completed cases , the figures were 4.71 days/month ( 95 % CI : 4.52–4.90 ) in the GG group and 5.67 days/month ( 95 % CI : 5.40–5.94 ) in the placebo group ( IRR 0.83 ; 95 % CI : 0.78–0.88 ; P<0.001 ) . Conclusions : Consumption of GG reduced the occurence of respiratory illness in children attending day care centers in the completed cases subgroup , but not in the total population . Thus , future clinical trials are warranted to clarify the association between fecal recovery of a probiotic and the symptom prevalence Background : It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections ( UTIs ) , bacterial sepsis and necrotizing enterocolitis ( NEC ) in preterm infants . Methods : A double-blind study was conducted in 12 Italian NICUs . Newborn infants with a gestational age <33 weeks or birthweight < 1,500 g were r and omized to receive st and ard milk feed supplemented with Lactobacillus GG ( Dicoflor ® , Dicofarm , Rome , Italy ) in a dose of 6 × 109 colony-forming units ( cfu ) once a day until discharge , starting with the first feed or placebo . Results : Five hundred eighty-five patients were studied . The probiotics group ( n = 295 ) and the placebo group ( n = 290 ) exhibited similar clinical characteristics . The duration of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days , respectively . Although UTIs ( 3.4 vs. 5.8 % ) and NEC ( 1.4 vs. 2.7 % ) were found less frequently in the probiotic group compared to the control group , these differences were not significant . Bacterial sepsis was more frequent in the probiotics group ( 4.4 % , n = 11 ) than in the placebo group ( 3.8 % , n = 9 ) , but the difference was not significant . Conclusion : Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs , NEC and sepsis in preterm infants . Further studies are required to confirm our results in lower birthweight population Lactobacillus rhamnosus GG , ATCC ( LGG ) , has shown antagonism to many bacteria including mutans streptococci . This r and omized , double – blind , placebo – controlled intervention study was design ed to examine whether milk containing LGG has an effect on caries and the risk of caries in children when compared with normal milk . 594 children , 1–6 years old , from 18 municipal day – care centres were included . The children received the milk with meals from coded containers 5 days a week in the day – care centres for 7 months . The children ’s oral health was recorded at baseline and at the end , using WHO criteria . The caries risk was calculated based on clinical and microbiological data , comprising mutans streptococcus levels from dental plaque and saliva . The risk was classified as high if the child had a dmft/DMFT or initial caries score > 0 , and a mutans streptococcus count ≧105 CFU/ml . The results showed less dental caries in the LGG group and lower mutans streptococcus counts at the end of the study . LGG was found to reduce the risk of caries significantly ( OR = 0.56 , p = 0.01 ; controlled for age and gender , OR = 0.51 , p = 0.004 ) . The effect was particularly clear in the 3– to 4–year – olds . Thus , milk containing the probiotic LGG bacteria may have beneficial effects on children ’s dental health Background : Probiotic Lactobacillus reuteri and reduced allergen load may lessen the daily crying of colic infants , but the role of Lactobacillus rhamnosus GG ( LGG ) has remained obscure . Methods : Infants with colic ( n = 30 ) were enrolled during the first 6 wk of life . All families received behavioral support and allergen avoidance diet : breastfeeding mothers followed cow ’s milk elimination diet and formula-fed infants received extensively hydrolyzed casein formula . The r and omized , double-blind intervention employed of LGG 4.5 × 109 cfu/d or placebo for a 4-wk study period . Daily crying was recorded by diaries and parental interviews . Fecal calprotectin and gut microbiota composition by quantitative PCR were evaluated before and after the intervention . Results : Daily crying time was comparable between the probiotic ( 173 min ) and the placebo group ( 174 min ; P = 0.99 ) at the end of the intervention according to the parental diary . However , parents reported a decrease of 68 % ( 95 % confidence interval ( CI ) : 58–78 ) in daily crying in the probiotic and 49 % ( 95 % CI : 32–66 ) in the placebo group ( P = 0.05 ) . Conclusion : LGG in infants treated in t and em with behavioral support and a cow ’s milk elimination diet did not provide additional treatment effect for diary-verified colic crying although parental report of crying suggested the probiotic intervention effective Background : Preliminary trials of probiotics in preventing recurrent chronic pouchitis have been encouraging Objective : To determine the effectiveness of Lactobacillus GG ( LGG ) in children with Helicobacter pylori infection undergoing eradication therapy . Material s and Methods : We conducted a double-blind , placebo-controlled , r and omized trial comparing a 7-day , triple eradication regimen consisting of 2 antibiotics ( amoxicillin tablets , 25 mg/kg twice per day , and clarithromycin tablets , 10 mg/kg twice per day ) plus a proton pump inhibitor ( omeprazole capsules , 0.5 mg/kg twice per day ) supplemented with LGG ( 109 colony-forming units ) or placebo in 83 children with H pylori infection confirmed by 2 of 3 tests ( 13C-urea breath test , histopathology , rapid urease test ) . The primary outcome measure was the H pylori eradication rate . The secondary outcome measure was the proportion of patients who experienced therapy-related adverse effects during anti – H pylori treatment . Results : The groups did not differ with respect to H pylori eradication rates . Of the 34 children in the LGG group , 23 ( 69 % ) experienced eradication , compared with 22 of 32 children ( 68 % ) in the placebo group ( RR 0.98 , 95 % CI 0.7–1.4 ) . The groups did not differ with respect to adverse effects . Conclusions : In children with H pylori infection , supplementation of st and ard triple therapy with LGG did not significantly alter the eradication rate or side effects Goals : To evaluate the efficacy of Lactobacillus rhamnosus GG ( LGG ) supplementation in eliminating the gastrointestinal carrier state of vancomycin-resistant enterococci ( VRE ) in colonized children , and to evaluate the affect of the probiotic on Lactobacillus spp . counts in the gastrointestinal tract . Study : A r and omized , single-blind , placebo-controlled study . Children ( 0 to 18 y old ) hospitalized at the wards of the children ’s hospital who were diagnosed with gastrointestinal carrier state of VRE were r and omized to group receiving 3 billion colony forming unit of LGG/day or placebo for 21 consecutive days . A total of 61 children completed the study ( 32 in the treatment group and 29 in the control group ) . Rectal swabs for VRE and Lactobacillus spp . were collected at baseline , during supplementation at weekly intervals and 1 month after supplementation . Antibiotic supply was controlled throughout the duration of the analysis . Results : A significant difference in the number of children colonized with VRE between the groups was observed at 3 weeks ( P=0.002 ) . The VRE carrier state was lost by 20 of 32 participants in the treatment group and 7 of 29 in the control group . We also observed increased gastrointestinal counts of Lactobacillus spp . in children receiving LGG . A statistically significant difference in the occurrence of bacteria was observed from week 1 onwards , whereas in the aspect of growth intensity from week 2 onwards . Conclusions : LGG supplementation temporarily eliminates the VRE carrier state and increases gastrointestinal counts of Lactobacillus spp . in children versus placebo BACKGROUND Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants , the mechanisms are unclear , and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants . OBJECTIVE The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight . DESIGN In a bicentric , double-blind , r and omized controlled clinical trial that was stratified for center and birth weight , 45 infants received enteral probiotics ( Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG ; BB536-LGG ) and 49 received placebo . The primary endpoint was the percentage of infants receiving > 50 % of their nutritional needs via enteral feeding on the 14th day of life . A triangular test was used to perform sequential analysis . RESULTS The trial was discontinued after the fourth sequential analysis concluded a lack of effect . The primary endpoint was not significantly different between the probiotic ( 57.8 % ) and placebo ( 57.1 % ) groups ( P = 0.95 ) . However , in infants who weighed > 1000 g , probiotic supplementation was associated with a shortening in the time to reach full enteral feeding ( P = 0.04 ) . Other than colonization by the probiotic strains , no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed . No colonization by probiotic strains was detected in infants who weighed < or = 1000 g , presumably because of more frequent suspensions of enteral feeding , more courses of antibiotic treatment , or both . CONCLUSIONS Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing > 1000 g. This trial was registered at clinical trials.gov as NCT 00290576 Abstract Background Viral upper respiratory tract infections occur frequently among conscripts . Probiotics have reduced viral infections in children attending day care . Limited data are available on the effects of probiotics on the nasopharyngeal presence of respiratory viruses . Objectives To assess , whether probiotics could decrease nasopharyngeal occurrence of respiratory viruses in Finnish conscripts . Study design In a r and omized , double-blind , placebo-controlled 90- and 150-day intervention study , 239 nasopharyngeal swab sample s were collected from 192 symptomatic conscripts receiving daily chewable probiotic tablet containing Lactobacillus rhamnosus GG and Bifidobacterium animalis ssp . lactis BB-12 ( 46.9 % ) or control tablet ( 53.1 % ) on visits to a garrison 's health care center due to symptoms of infection . The presence of respiratory viruses was tested by PCR- methods , and viral findings were compared between the intervention groups . Results 184 ( 76.9 % ) nasopharyngeal sample s were positive for at least one respiratory virus . Picornaviruses were the most common viruses and were detected in 155 ( 84.2 % ) of sample s. Of these , 143 ( 92.3 % ) were rhinovirus-positive and 20 ( 12.9 % ) were enterovirus-positive . The control group had 83 ( 64 % ) and the probiotic group 72 ( 66 % ) picornavirus infections ( p = 0.79 ) . Monthly distribution of picornaviruses showed that there were less picornavirus findings after 3 months in the probiotic group than in the control group ( p = 0.0069 ) . However , probiotics did not reduce picornavirus occurrence in other months . Conclusions Overall , probiotics did not reduce viral occurrence in symptomatic conscripts . However , probiotics decreased the presence of picornaviruses after 3 months , which may imply that probiotics play a role against viruses causing common cold . Further investigations are necessary to clarify the mechanisms involved in order to target specific probiotics on specific respiratory viruses A novel combination of culturing and DNA-based terminal restriction fragment length polymorphism ( TRFLP ) analysis was used to investigate the effect of probiotics on antibiotic-induced gut microbiota alterations to determine if a probiotic preparation containing bifidobacteria and lactobacilli , taken during and after antibiotic therapy , can minimize antibiotic disturbance of faecal microbiota . Healthy subjects administered amoxicillin/clavulanate were r and omized and concomitantly received a placebo or probiotic mixture . The primary end point was similarity of faecal microbiota as determined by culturing and TRFLP from subjects taking probiotics compared to those taking a placebo measured by comparing data from baseline to post-treatment for each subject . TRFLP analysis revealed a high subject to subject variation in the baseline faecal microbiota . The most common antibiotic-induced disturbance was a relative increase in Clostridium , Eubacterium , Bacteroides and Enterobacteraceae . The mean similarity to the baseline increased over time in both treatment groups , although the probiotic group was less disturbed according to both TRFLP and culture data . The culture method revealed that post-antibiotic faecal microbiota in probiotic-consuming subjects were more similar to the baseline microbiota than the control group ( P=0.046 ) . Changes in Enterobactereaceae ( P=0.006 ) and Bifidobacterium ( P=0.030 ) counts were significantly different between the groups . Analysis of TRFLP data reinforced the trend between groups but was not statistically significant ( P=0.066 ) . This study indicates this mixture of probiotics promotes a more rapid return to pre-antibiotic baseline faecal bacterial microbiota Synbiotic supplements , which contain multiple functional ingredients , may enhance the immune system more than the use of individual ingredients alone . A double blind active controlled parallel trial over a 21 day exercise training period was conducted to evaluate the effect of Gut BalanceTM , which contains Lactobacillus paracasei subsp paracasei ( L. casei 431 ® ) , Bifidobacterium animalis ssp lactis ( BB-12 ® ) , Lactobacillus acidophilus ( LA-5 ® ) , Lactobacillus rhamnosus ( LGG ® ) , two prebiotics ( raftiline and raftilose ) and bovine whey derived lactoferrin and immunoglobulins with acacia gum on fecal microbiota , short chain fatty acids ( SCFA ) , gut permeability , salivary lactoferrin and serum cytokines . All subjects r and omized were included in the analysis . There was a 9-fold ( 1.2-fold to 64-fold ; 95 % confidence intervals p = 0.03 ) greater increase in fecal L. paracasei numbers with Gut BalanceTM compared with acacia gum supplementation . Gut BalanceTM was associated with a 50 % ( -12 % to 72 % ; p = 0.02 ) smaller increase in the concentration of serum IL-16 in comparison to acacia gum from pre- to post- study . No substantial effects of either supplement were evident in fecal SCFA concentrations , measures of mucosal immunity or GI permeability . Clinical studies are now required to determine whether Gut BalanceTM may exert beneficial GI health effects by increasing the recovery of fecal L. paracasei . Both supplements had little effect on immunity . Twenty-two healthy physically active male subjects ( mean age = 33.9 ± 6.5 y ) were r and omly allocated to either daily prebiotic or synbiotic supplementation for 21 day . Saliva , blood , urine and fecal sample s were collected pre- , mid- and post-intervention . Participants recorded patterns of physical activity on a self-reported question naire OBJECTIVE To assess the effect of probiotics on the incidence of necrotizing enterocolitis ( NEC ) in premature infants born to human immunodeficiency virus (HIV)-positive and HIV-negative women . PATIENTS AND METHODS HIV-exposed and HIV-unexposed premature infants were r and omized to either the probiotic or the placebo group . The probiotic consisted of 1 × 10(9 ) colony-forming units , Lactobacillus rhamnosus GG and Bifidobacterium infantis per day . RESULTS In total , 74 HIV-exposed and 110 HIV-unexposed infants were enrolled and r and omized . The incidence of death [ 4 ( 5.4 % ) vs. 7 ( 6 % ) ; p = 0.79 ] and NEC [ 4 ( 5 % ) vs. 5 ( 5 % ) ; p = 0.76 ] did not differ significantly between the HIV-exposed and HIV-unexposed groups . A significant difference was found for total NEC incidence between the study and control groups [ 3 ( 3 % ) vs. 6 ( 6 % ) ; p = 0.029 ] . The incidence of NEC in the HIV-exposed group differed significantly [ Bells I 2 ( 5 % ) vs. Bells III 2 ( 5 % ) ; p = 0.045 ) . CONCLUSION Probiotic supplementation reduced the incidence of NEC in the premature very low birth weight infants ; however , results failed to show a lower incidence of NEC in HIV-exposed premature infants . A reduction in the severity of disease was found in the HIV-exposed study group One‐week triple therapy is currently considered the golden st and ard against Helicobacter pylori . However , gastrointestinal side‐effects are among the major pitfalls in such regimens . Probiotic supplementation might help to prevent or reduce such drug‐related manifestations Purpose Probiotics have been shown to be able to restore a non-pathogenic digestive flora , to prevent digestive colonization by pathogenic bacteria , and to modulate immunity . The aim of this study was to assess the effects of prophylactic probiotic administration in patients ventilated for up to 2 days . Methods This study was performed as a double-blind , concealed r and omized , placebo-controlled trial in a French medical intensive care unit ( ICU ) . Adult patients mechanically ventilated for a period of more than 48 h received enterally administered probiotics ( Ergyphilus ® , 2 × 1010 lactic acid bacteria , mostly Lactobacillus rhamnosus GG , once a day ) or placebo until successful weaning . Results A total of 167 patients were included . The two groups were comparable at baseline . The 28-day mortality rates were not different in the probiotic ( 25.3 % ) and placebo groups ( 23.7 % ) . Mortality rates in ICU and at 90 days were also unaffected by the treatment . The incidence of ICU-acquired infections did not differ significantly except for that of catheter-related bloodstream infections that was lowered by probiotics . On a prespecified subgroup analysis , we found a reduction of the 28-day mortality among severe sepsis patients ( total n = 101 ) treated with probiotics ( n = 52 ) with an odds ratio ( OR ) for death at 0.38 ( 95 % CI 0.16–0.93 , p = 0.035 ) . By contrast , probiotics were associated with a higher mortality rate in non-severe sepsis patients ( OR 3.09 , 95 % CI 0.87–11.01 , p = 0.08 ) . Conclusions Although numerous uncertainties remain ( type and the number of strains to use , delay and length of administration ) , and despite an acceptable safety profile , the daily prophylactic administration of probiotics can not be encouraged in the critically ill patient This was a r and omized controlled pilot study of Lactobacillus rhamnosus GG versus st and ard of care to prevent gastrointestinal multidrug-resistant organism colonization in intensive care unit patients . Among 70 subjects , there were no significant differences in acquisition or loss of any multidrug-resistant organisms ( P>.05 ) and no probiotic-associated adverse events Objectives : Recurrent cholangitis may aggravate cholestatic liver cirrhosis in biliary atresia ( BA ) after the Kasai operation . This pilot study aim ed to investigate whether Lactobacillus casei rhamnosus has the prophylactic efficacy for recurrent cholangitis in comparison with the conventional neomycin prophylaxis . Methods : Twenty jaundice-free patients with BA ages 0 to 3 years who underwent a Kasai operation were enrolled and r and omized into 2 groups with 10 patients each : neomycin ( 25 mg · kg−1 · day−1 for 4 days/wk ) and L casei rhamnosus ( 8 × 108 colony-forming unit per day ) groups . The treatment duration was 6 months . Bacterial stool cultures were performed before treatment and 1 , 3 , and 6 months after starting treatment . In addition , 10 patients with BA with similar status but without prophylaxis served as the historical control group . Results : In the Lactobacillus group , 2 patients ( 20 % , mean 0.03 ± 0.07 episodes per month ) developed cholangitis during the study period , with the same frequency as in the neomycin group and significantly lower than that in the control group ( 80 % , P = 0.005 , mean 0.22 ± 0.16 episodes per month ) . The mean change in body weight z score during the 6 months in the Lactobacillus group was 0.97 ± 0.59 , which was significantly better than that in the control group ( −0.01 ± 0.79 , P = 0.006 ) . In bacterial stool cultures , the Lactobacillus and Escherichia coli population s significantly increased and decreased , respectively , in the Lactobacillus group . Conclusions : The use of L casei rhamnosus was as effective as neomycin in preventing cholangitis in patients with BA who underwent Kasai operation , and therefore could be considered as a potential alternative prophylactic regimen AIM To investigate the effects of a low fermentable , oligosaccharides , disaccharides , monosaccharides and polyols diet ( LFD ) and the probiotic Lactobacillus rhamnosus GG ( LGG ) in irritable bowel syndrome ( IBS ) . METHODS R and omised , unblinded controlled trial on the effect of 6-wk treatment with LFD , LGG or a normal Danish/Western diet ( ND ) in patients with IBS fulfilling Rome III diagnostic criteria , recruited between November 2009 and April 2013 . Patients were required to complete on a weekly basis the IBS severity score system ( IBS-SSS ) and IBS quality of life ( IBS-QOL ) question naires in a specially developed IBS web self-monitoring application . We investigated whether LFD or LGG could reduce IBS-SSS and improve QOL in IBS patients . RESULTS One hundred twenty-three patients ( median age 37 years , range : 18 - 74 years ) , 90 ( 73 % ) females were r and omised : 42 to LFD , 41 to LGG and 40 to ND . A significant reduction in mean ± SD of IBS-SSS from baseline to week 6 between LFD vs LGG vs ND was revealed : 133 ± 122 vs 68 ± 107 , 133 ± 122 vs 34 ± 95 , P < 0.01 . Adjusted changes of IBS-SSS for baseline covariates showed statistically significant reduction of IBS-SSS in LFD group compared to ND ( IBS-SSS score 75 ; 95%CI : 24 - 126 , P < 0.01 ) , but not in LGG compared to ND ( IBS-SSS score 32 ; 95%CI : 18 - 80 , P = 0.20 ) . IBS-QOL was not altered significantly in any of the three groups : mean ± SD in LFD 8 ± 18 vs LGG 7 ± 17 , LFD 8 ± 18 vs ND 0.1 ± 15 , P = 0.13 . CONCLUSION Both LFD and LGG are efficatious in patients with IBS The present r and omised , double-blind , placebo-controlled study was conducted to determine whether consumption of probiotic Lactobacillus rhamnosus GG ( GG ) would lead to the recovery of GG in tonsil tissue . After 3 weeks ’ daily consumption of GG as a single strain ( n 20 ) , GG as a part of a multispecies combination ( n 17 ) or placebo ( n 20 ) , tonsil tissue sample s were collected from fifty-seven young adults during tonsillectomy due to chronic or recurrent tonsillitis . Strain-specific real-time PCR was used to detect GG in the tonsil tissue . GG was recovered in the tonsil sample of 40 % of the subjects in the GG group , 41 % in the multispecies group and 30 % in the placebo group ( P value between groups 0.79 ) . In all subjects with positive recovery of GG in the tonsil tissue , GG was also recovered in the faecal sample taken at the start of the intervention and at the time of the tissue sample collection , which indicates more persistent adherence of the probiotic . To conclude , GG can be recovered from tonsil tissue after oral administration as a singlestrain probiotic or as a part of a multispecies probiotic combination . The present results suggest that individual variation exists in the ability of GG to adhere to tonsil tissue . Persistence of GG appears to be high in tonsil tissue as well , in addition to persistence in faecal sample s , which has been demonstrated previously . Further clinical trials are warranted to evaluate whether probiotic adherence in the tonsil tissue could have a role in respiratory symptom prevalence ABSTRACT Vancomycin-resistant enterococci ( VRE ) are endemic in health care setting s. These organisms colonize the gastrointestinal tract and can lead to infection which is associated with increased mortality . There is no treatment for VRE colonization . We conducted a r and omized , double-blind , placebo-controlled clinical trial to examine the safety and efficacy of administration of the probiotic Lactobacillus rhamnosus GG ( LGG ) for the reduction or elimination of intestinal colonization by VRE . Colonized adults were r and omized to receive LGG or placebo for 14 days . Quantitative stool cultures for LGG and VRE were collected at baseline and days 7 , 14 , 21 , 28 , and 56 . Day 14 stool sample s from some subjects were analyzed by quantitative PCR ( qPCR ) for LGG . Patients were closely monitored for adverse events . Eleven subjects , of whom 5 received LGG and 6 received placebo , were analyzed . No differences in VRE colony counts were seen at any time points between groups . No decline in colony counts was seen over time in subjects who received LGG . LGG was detected by PCR in all sample s tested from subjects who received LGG but was only isolated in culture from 2 of 5 subjects in the LGG group . No treatment-related adverse events were seen . We demonstrated that LGG could be administered safely to patients with comorbidities and is recoverable in some patients ' stool cultures . Concomitant administration of antibiotics may have result ed in an inability to recover viable organisms from stool sample s , but LGG DNA could still be detected by qPCR . LGG administration did not affect VRE colonization in this study . ( This study was registered at Clinical trials.gov under registration no. NCT00756262 . BACKGROUND & AIMS The aim of our study was to investigate the role of Lactobacillus GG ( LGG ) in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in 281 children who attend day care centers . They were r and omly allocated to receive LGG at a dose of 10(9 ) colony-forming units in 100ml of a fermented milk product ( LGG group , n=139 ) or placebo that was the same post-pasteurized fermented milk product without LGG ( placebo group , n=142 ) during the 3-month intervention period . RESULTS Compared to the placebo group , children in the LGG group had a significantly reduced risk of upper respiratory tract infections ( RR 0.66 , 95 % CI 0.52 to 0.82 , NNT 5 , 95 % CI 4 to 10 ) , a reduced risk of respiratory tract infections lasting longer than 3 days ( RR 0.57 , 95 % CI 0.41 to 0.78 , NNT 5 , 95 % CI 4 to 11 ) , and a significantly lower number of days with respiratory symptoms ( p<0.001 ) . There was no risk reduction in regard to lower respiratory tract infections ( RR 0.82 , 95 % CI 0.24 to 2.76 ) . Compared with the placebo group , children in the LGG group had no significant reduction in the risk of gastrointestinal infections ( RR 0.63 , 95 % CI 0.38 to 1.06 ) , vomiting episodes ( RR 0.60 , 95 % CI 0.29 to 1.24 ) , and diarrheal episodes ( RR 0.63 , 95 % CI 0.35 to 1.11 ) as well as no reduction in the number of days with gastrointestinal symptoms ( p=0.063 ) . CONCLUSION LGG administration can be recommended as a valid measure for decreasing the risk of upper respiratory tract infections in children attending day care centers OBJECTIVE : Our aim was to determine whether Lactobacillus rhamnosus GG ( LGG ) relieves symptoms in children with recurrent abdominal pain . PATIENTS AND METHODS : A total of 141 children with irritable bowel syndrome ( IBS ) or functional pain were enrolled in 9 primary care sites and a referral center . Children entered a r and omized , double-blind , placebo-controlled trial and received LGG or placebo for 8 weeks and entered follow-up for 8 weeks . The primary outcome was overall pain at the end of the intervention period . At entry and at the end of the trial , children underwent a double-sugar intestinal permeability test . RESULTS : Compared with baseline , LGG , but not placebo , caused a significant reduction of both frequency ( P < .01 ) and severity ( P < .01 ) of abdominal pain . These differences still were significant at the end of follow-up ( P < .02 and P < .001 , respectively ) . At week 12 , treatment success was achieved in 48 children in the LGG group compared with 37 children in the placebo group ( P < .03 ) ; this difference still was present at the end of follow-up ( P < .03 ) . At entry , 59 % of the children had abnormal results from the intestinal permeability test ; LGG , but not placebo , determined a significant decrease in the number of patients with abnormal results from the intestinal permeability testing ( P < .03 ) . These effects mainly were in children with IBS . CONCLUSIONS : LGG significantly reduces the frequency and severity of abdominal pain in children with IBS ; this effect is sustained and may be secondary to improvement of the gut barrier |
2,184 | 26,832,915 | In addition , EMPA as add-on to MET also had a favourable effect on body weight and blood pressure .
Conclusions EMPA as add-on to MET was well tolerated and provided additional benefits beyond glucose lowering , such as weight loss and blood pressure reduction . | Purpose To assess the efficacy and safety of empagliflozin ( EMPA ) as add-on to metformin ( MET ) in patients with type 2 diabetes mellitus ( T2DM ) . | Patients with type 2 diabetes mellitus ( T2DM ) with a glycated haemoglobin ( HbA1c ) level ≥7 and ≤10 % were r and omized to receive empagliflozin 12.5 mg twice daily ( n = 219 ) , 25 mg once daily ( n = 218 ) , 5 mg twice daily ( n = 219 ) or 10 mg once daily ( n = 220 ) , or placebo ( n = 107 ) as add‐on to stable‐dose metformin immediate release ( IR ) twice daily for 16 weeks . The primary endpoint was change from baseline in HbA1c at week 16 . At week 16 , change from baseline in HbA1c with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa . The adjusted mean ( 95 % confidence interval ) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11 % ( −0.26 , 0.03 ) , and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02 % ( −0.16 , 0.13 ) . All empagliflozin regimens were well tolerated ; thus , when used as add‐on to metformin IR in patients with T2DM , the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent OBJECTIVE To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin . RESEARCH DESIGN AND METHODS Subjects were r and omized to a combination of empagliflozin 25 mg/linagliptin 5 mg ( n = 137 ) , empagliflozin 10 mg/linagliptin 5 mg ( n = 136 ) , empagliflozin 25 mg ( n = 141 ) , empagliflozin 10 mg ( n = 140 ) , or linagliptin 5 mg ( n = 132 ) as add-on to metformin for 52 weeks . The primary end point was change from baseline in HbA1c at week 24 . RESULTS At week 24 , reductions in HbA1c ( mean baseline 7.90–8.02 % [ 62.8–64.1 mmol/mol ] ) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin ; adjusted mean ( SE ) changes from baseline were −1.19 % ( 0.06 ) ( −13.1 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg/linagliptin 5 mg , −1.08 % ( 0.06 ) ( −11.8 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg/linagliptin 5 mg , −0.62 % ( 0.06 ) ( −6.8 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg , −0.66 % ( 0.06 ) ( −7.2 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg , and −0.70 % ( 0.06 ) ( −7.6 mmol/mol [ 0.7 ] ) with linagliptin 5 mg ( P < 0.001 for all comparisons ) . In these groups , respectively , 61.8 , 57.8 , 32.6 , 28.0 , and 36.1 % of subjects with baseline HbA1c ≥7 % ( ≥53 mmol/mol ) had HbA1c < 7 % ( < 53 mmol/mol ) at week 24 . Efficacy was maintained at week 52 . The proportion of subjects with adverse events ( AEs ) over 52 weeks was similar across treatment arms ( 68.6–73.0 % ) , with no hypoglycemic AEs requiring assistance . CONCLUSIONS Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated Background Despite the number of medications for type 2 diabetes , many people with the condition do not achieve good glycaemic control . Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia . Type 2 diabetes tends to be a progressive disease , and most patients require treatment with combinations of glucose-lowering agents . The sodium glucose co-transporter 2 ( SGLT2 ) receptor inhibitors are a new class of glucose-lowering agents . Objective To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes . Data sources MEDLINE , Embase , Cochrane Library ( all sections ) ; Science Citation Index ; trial registries ; conference abstract s ; drug regulatory authorities ; bibliographies of retrieved papers . Inclusion criteria R and omised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy . Methods Systematic review . Quality assessment used the Cochrane risk of bias score . Results Seven trials , published in full , assessed dapagliflozin and one assessed canagliflozin . Trial quality appeared good . Dapagliflozin 10 mg reduced HbA1c by −0.54 % ( weighted mean differences ( WMD ) , 95 % CI −0.67 to −0.40 ) compared to placebo , but there was no difference compared to glipizide . Canagliflozin reduced HbA1c slightly more than sitagliptin ( up to −0.21 % vs sitagliptin ) . Both dapagliflozin and canagliflozin led to weight loss ( dapagliflozin WMD −1.81 kg ( 95 % CI −2.04 to −1.57 ) , canagliflozin up to −2.3 kg compared to placebo ) . Limitations Long-term trial extensions suggested that effects were maintained over time . Data on canagliflozin are currently available from only one paper . Costs of the drugs are not known so cost-effectiveness can not be assessed . More data on safety are needed , with the Food and Drug Administration having concerns about breast and bladder cancers . Conclusions Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes , although more safety data are needed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To investigate the long-term safety and efficacy of empagliflozin , a sodium glucose cotransporter 2 inhibitor ; sitagliptin ; and metformin in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS In this r and omized , open-label , 78-week extension study of two 12-week , blinded , dose-finding studies of empagliflozin ( monotherapy and add-on to metformin ) with open-label comparators , 272 patients received 10 mg empagliflozin ( 166 as add-on to metformin ) , 275 received 25 mg empagliflozin ( 166 as add-on to metformin ) , 56 patients received metformin , and 56 patients received sitagliptin as add-on to metformin . RESULTS Changes from baseline in HbA1c at week 90 were −0.34 to −0.63 % ( −3.7 to −6.9 mmol/mol ) with empagliflozin , −0.56 % ( −6.1 mmol/mol ) with metformin , and −0.40 % ( −4.4 mmol/mol ) with sitagliptin . Changes from baseline in weight at week 90 were −2.2 to −4.0 kg with empagliflozin , −1.3 kg with metformin , and −0.4 kg with sitagliptin . Adverse events ( AEs ) were reported in 63.2–74.1 % of patients on empagliflozin and 69.6 % on metformin or sitagliptin ; most AEs were mild or moderate in intensity . Hypoglycemic events were rare in all treatment groups , and none required assistance . AEs consistent with genital infections were reported in 3.0–5.5 % of patients on empagliflozin , 1.8 % on metformin , and none on sitagliptin . AEs consistent with urinary tract infections were reported in 3.8–12.7 % of patients on empagliflozin , 3.6 % on metformin , and 12.5 % on sitagliptin . CONCLUSIONS Long-term empagliflozin treatment provided sustained glycemic and weight control and was well tolerated with a low risk of hypoglycemia in patients with type 2 diabetes Chronic hyperglycemia impairs insulin action , result ing in glucotoxicity , which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors . Here , we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes . Eighteen diabetic men were r and omized to receive either dapagliflozin ( n = 12 ) or placebo ( n = 6 ) for 2 weeks . We measured insulin-mediated whole body glucose uptake and endogenous glucose production ( EGP ) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique . Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose . Insulin-mediated tissue glucose disposal increased by approximately 18 % after 2 weeks of dapagliflozin treatment , while placebo-treated subjects had no change in insulin sensitivity . Surprisingly , following dapagliflozin treatment , EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration . Together , our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity . However , glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP . These results provide support for the glucotoxicity hypothesis , which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes AIMS To evaluate the effects of the sodium glucose cotransporter 2 ( SGLT2 ) inhibitor empagliflozin added to metformin for 12 weeks in patients with type 2 diabetes . METHODS This dose-ranging , double-blind , placebo-controlled trial r and omized 495 participants with type 2 diabetes inadequately controlled on metformin [ haemoglobin A1c ( HbA1c ) > 7 to ≤10 % ] to receive 1 , 5 , 10 , 25 , or 50 mg empagliflozin once daily ( QD ) , or placebo , or open-label sitagliptin ( 100 mg QD ) , added to metformin for 12 weeks . The primary endpoint was change in HbA1c from baseline to week 12 ( empagliflozin groups versus placebo ) . RESULTS Reductions in HbA1c of -0.09 to -0.56 % were observed with empagliflozin after 12 weeks , versus an increase of 0.15 % with placebo ( baseline : 7.8 - 8.1 % ) . Compared with placebo , empagliflozin doses from 5 to 50 mg result ed in reductions in fasting plasma glucose ( -2 to -28 mg/dl vs. 5 mg/dl with placebo ; p < 0.0001 ) and body weight ( -2.3 to -2.9 kg vs. -1.2 kg ; p < 0.01 ) . Frequency of adverse events was generally similar with empagliflozin ( 29.6 - 48.6 % ) , placebo ( 36.6 % ) and sitagliptin ( 35.2 % ) . Hypoglycaemia rates were very low and balanced among groups . Most frequent adverse events with empagliflozin were urinary tract infections ( 4.0 % vs. 2.8 % with placebo ) and pollakiuria ( 2.5 % vs. 1.4 % with placebo ) . Genital infections were reported only with empagliflozin ( 4.0 % ) . CONCLUSIONS Once daily empagliflozin as add-on therapy to metformin was well tolerated except for increased genital infections and result ed in reductions in HbA1c , fasting plasma glucose and body weight in patients with type 2 diabetes inadequately controlled on metformin monotherapy To investigate the long‐term efficacy and safety of empagliflozin as add‐on to metformin in people with Type 2 diabetes Background Empagliflozin is a potent , selective inhibitor of sodium glucose cotransporter 2 in development for the treatment of patients with type 2 diabetes mellitus . Oral contraceptives may be co-administered with antidiabetic agents over long periods of time , therefore potential drug-drug interactions between oral contraceptives and antidiabetic drugs should be investigated . Objective The effect of multiple oral doses of empagliflozin 25 mg once daily ( qd ) on the steady-state pharmacokinetics of the combined oral contraceptive ethinylestradiol ( EE ) 30 μg/levonorgestrel ( LNG ) 150 μg qd was investigated . Study Design This was a phase I , open-label , two-period , fixed sequence study . Setting The study was performed at the Human Pharmacology Centre/Department of Translational Medicine , Boehringer Ingelheim , Biberach , Germany . Participants Eighteen healthy premenopausal women participated in the study .InterventionThere was a m and atory run-in period in which participants received EE 30 μg/LNG 150 μg qd for 21–48 days followed by a treatment-free interval of 7 days . Participants then received EE 30 μg/LNG 150 μg qd for 14 days ( reference ; period 1 ) , followed by EE 30 μg/LNG 150 μg qd plus empagliflozin 25 mg qd for 7 days ( test ; period 2).Main Outcome Measures The pharmacokinetics of EE and LNG at steady state based on the primary endpoints of area under the steady-state plasma concentration-time curve during a dosage interval τ ( AUCτ , ss ) and maximum steady-state plasma concentration during a dosage interval ( Cmax , ss ) were the main outcome measures . Results The pharmacokinetics of EE and LNG were not affected by co-administration with empagliflozin . Geometric mean ratios ( 90 % CI ) of AUCτ , ss and Cmax , ss for EE were 102.82 % ( 97.58 , 108.35 ) and 99.22 % ( 93.40 , 105.39 ) , respectively . For LNG , these values were 101.94 % ( 98.54 , 105.47 ) and 105.81 % ( 99.47 , 112.55 ) , respectively . The 90 % CIs were within the st and ard bioequivalence boundaries of 80–125 % . There were no relevant changes in the time to reach peak levels ( tmax , ss ) or terminal elimination half-life ( t½,ss ) of EE and LNG between test and reference treatments . Ten women in each treatment had at least one adverse event ( AE ) . Severe AEs were reported by three women in the reference period and one woman in the test period . There were no serious AEs or premature discontinuations . Conclusion The combination of EE 30 μg/LNG 150 μg and empagliflozin 25 mg was well tolerated . Based on st and ard bioequivalence criteria , empagliflozin had no effect on the pharmacokinetics of EE and LNG , indicating that no dose adjustment of EE 30 μg/LNG 150 μg is required when empagliflozin is co-administered BACKGROUND Metformin is the recommended first-line pharmacotherapy for patients with type 2 diabetes . There is no consensus on the optimum second-line pharmacotherapy . We compared the efficacy and safety of the sodium glucose cotransporter 2 inhibitor empagliflozin and the sulfonylurea glimepiride as add-on to metformin in patients with type 2 diabetes . METHODS In this double-blind phase 3 trial , patients ( aged ≥18 years ) with type 2 diabetes and HbA1c concentrations of 7 - 10 % , despite metformin treatment and diet and exercise counselling , were r and omly assigned in a 1:1 ratio with a computer-generated r and om sequence , stratified by HbA1c , estimated glomerular filtration rate ( eGFR ) , and region , to empagliflozin ( 25 mg once daily , orally ) or glimepiride ( 1 - 4 mg once daily , orally ) as add-on to metformin for 104 weeks . Patients and investigators were masked to treatment assignment . The primary endpoint was change from baseline in HbA1c levels at weeks 52 and 104 . Differences in the primary endpoint were first tested for non-inferiority ( based on a margin of 0·3 % ) . If non-inferiority was shown , differences in the primary endpoint at week 104 were then tested for superiority . Analysis was done on the full- analysis set-ie , patients who were treated with at least one dose of study drug and had a baseline HbA1c value . This study is registered with Clinical Trials.gov , number NCT01167881 . A 104-week extension is ongoing . FINDINGS Between August , 2010 , and June , 2011 , 1549 patients were r and omly assigned to receive empagliflozin ( n=769 ) or glimepiride ( n=780 ) ; four patients in the empagliflozin group did not receive the assigned treatment . Empagliflozin was non-inferior to glimepiride at both timepoints . At week 104 , adjusted mean difference in change from baseline in HbA1c with empagliflozin versus glimepiride was -0·11 % ( 95 % CI -0·19 to -0·02 ; p=0·0153 for superiority ) . Adverse events were reported in 661 ( 86 % ) patients treated with empagliflozin and 673 ( 86 % ) patients treated with glimepiride . Severe adverse events were reported in 72 ( 9 % ) patients in the empagliflozin group and 68 ( 9 % ) in the glimepiride group . Serious adverse events were reported in 119 ( 16 % ) patients in the empagliflozin group and 89 ( 11 % ) in the glimepiride group . Confirmed hypoglycaemic adverse events ( plasma glucose ≤3·9 mmol/L or requiring assistance ) at week 104 were reported in 19 ( 2 % ) patients treated with empagliflozin and 189 ( 24 % ) patients treated with glimepiride . INTERPRETATION Empagliflozin might be an effective and a well tolerated second-line treatment option for patients with type 2 diabetes who have not achieved good glycaemic control on metformin . FUNDING Boehringer Ingelheim and Eli Lilly BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes . We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors . METHODS In this r and omized study , 10,251 patients ( mean age , 62.2 years ) with a median glycated hemoglobin level of 8.1 % were assigned to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level from 7.0 to 7.9 % ) . Of these patients , 38 % were women , and 35 % had had a previous cardiovascular event . The primary outcome was a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up . RESULTS At 1 year , stable median glycated hemoglobin levels of 6.4 % and 7.5 % were achieved in the intensive-therapy group and the st and ard-therapy group , respectively . During follow-up , the primary outcome occurred in 352 patients in the intensive-therapy group , as compared with 371 in the st and ard-therapy group ( hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.78 to 1.04 ; P=0.16 ) . At the same time , 257 patients in the intensive-therapy group died , as compared with 203 patients in the st and ard-therapy group ( hazard ratio , 1.22 ; 95 % CI , 1.01 to 1.46 ; P=0.04 ) . Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group ( P<0.001 ) . CONCLUSIONS As compared with st and ard therapy , the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events . These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . |
2,185 | 25,875,025 | These effects were inversely associated with baseline BP values , and were robust in sensitivity analyses .
This meta- analysis of RCTs showed a significant effect of H. sabdariffa in lowering both SBP and DBP . | BACKGROUND Hibiscus sabdariffa L. is a tropical wild plant rich in organic acids , polyphenols , anthocyanins , polysaccharides , and volatile constituents that are beneficial for the cardiovascular system .
Hibiscus sabdariffa beverages are commonly consumed to treat arterial hypertension , yet the evidence from r and omized controlled trials ( RCTs ) has not been fully conclusive .
Therefore , we aim ed to assess the potential antihypertensive effects of H. sabdariffa through systematic review of literature and meta- analysis of available RCTs . | Hibiscus sabdariffa L. ( Malvaceae ) has been used in different countries as an antihypertensive . Pharmacological work has demonstrated that this effect is probably produced by a diuretic activity and inhibition of the angiotensin-converting enzyme ( ACE ) . Two clinical trials have confirmed the antihypertensive effect using watery infusions , in which a natriuretic effect was also detected . To compare therapeutic effectiveness , tolerability , and safety , as well as the effect on serum electrolytes and the ACE inhibitory effect of a herbal medicinal product prepared from the dried extract of H. sabdariffa calyxes ( HsHMP ) with those of lisinopril on patients with hypertension ( HT ) , a r and omized , controlled , and double-blind clinical trial was conducted . Patients of either sex , 25 - 61 years of age , with hypertension stage I or II , were daily treated for 4 weeks with the HsHMP , 250 mg of total anthocyanins per dose ( experimental group ) , or 10 mg of lisinopril ( control group ) . Outcome variables included effectiveness ( diastolic blood pressure [ DBP ] reduction , > or= 10 mmHg ) , safety ( absence of pathological modifications in the biochemical tests of hepatic and renal function ) , tolerability ( absence of intense side effects ) , effect on serum electrolytes , and effect on ACE activity . Basal analysis included 193 subjects ( 100 in the experimental group ) , while outcome variable analysis integrated 171 . Results showed that the experimental treatment decreased blood pressure ( BP ) from 146.48/97.77 to 129.89/85.96 mmHg , reaching an absolute reduction of 17.14/11.97 mmHg ( 11.58/12.21 % , p < 0.05 ) . The experimental treatment showed therapeutic effectiveness of 65.12 % as well as tolerability and safety of 100 % . BP reductions and therapeutic effectiveness were lower than those obtained with lisinopril ( p < 0.05 ) . Under the experimental treatment , the serum chlorine level increased from 91.71 to 95.13 mmol/L ( p = 0.0001 ) , the sodium level showed a tendency to decrease ( from 139.09 to 137.35 , p = 0.07 ) , while potassium level was not modified . ACE plasmatic activity was inhibited by HsHMP from 44.049 to 30.1 Units ( Us ; p = 0.0001 ) . In conclusion , the HsHMP exerted important antihypertensive effectiveness with a wide margin of tolerability and safety , while it also significantly reduced plasma ACE activity and demonstrated a tendency to reduce serum sodium ( Na ) concentrations without modifying potassium ( K ) levels . Further studies are necessary for evaluating the dose-dependency of HsHMP and for detecting lower effective doses ABSTRACT Introduction : The use of herbal medicines including different types of tea is among the different strategies for preventing and controlling the side-effects of diabetes . The aim of the present study was to compare the effect of sour tea and green tea on mildly hypertensive patients with diabetes . Methods : The present study was a r and omized clinical trial in which 100 mildly hypertensive patients with diabetes were r and omly assigned into sour tea group ( ST ) and green tea group ( GT ) . They were instructed to drink sour tea and green tea infusion , respectively , three times a day 2 hr after each meal for 4 weeks . The participants ’ blood pressure was measured at days 1 , 15 , and at the end of study . Results : The systolic pressure of both groups statistically decreased at the end of the study ; it decreased from 123.1 ± 15.5 to 116.8 ± 16.3 mmHg in the ST and from 119.4 ± 15.1 to 114.8 ± 15.9 mmHg in the GT . The diastolic pressure of both groups statistically decreased by the end of the study ; it decreased from 79.4 ± 11.1 to 74.5 ± 9.3 mmHg in the ST and from 78.9 ± 8.3 to 75.3 ± 7.7 mmHg in the GT . The therapeutic effectiveness of tea drinking by the end of intervention was 43.5 % in the ST and 39.6 % in the GT compared to the beginning . Conclusions : The present study revealed that mildly hypertensive type 2 diabetic individuals who drink three glasses of green or sour tea daily for 4 weeks show significant decreased systolic and diastolic blood pressures Epidemiological studies report that quercetin , an antioxidant flavonol found in apples , berries , and onions , is associated with reduced risk of coronary heart disease and stroke . Quercetin supplementation also reduces blood pressure in hypertensive rodents . The efficacy of quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated . We tested the hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients . We then determined whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress . Men and women with prehypertension ( n = 19 ) and stage 1 hypertension ( n = 22 ) were enrolled in a r and omized , double-blind , placebo-controlled , crossover study to test the efficacy of 730 mg quercetin/d for 28 d vs. placebo . Blood pressure ( mm Hg , systolic/diastolic ) at enrollment was 137 + /- 2/86 + /- 1 in prehypertensives and 148 + /- 2/96 + /- 1 in stage 1 hypertensive subjects . Blood pressure was not altered in prehypertensive patients after quercetin supplementation . In contrast , reductions in ( P < 0.01 ) systolic ( -7 + /- 2 mm Hg ) , diastolic ( -5 + /- 2 mm Hg ) , and mean arterial pressures ( -5 + /- 2 mm Hg ) were observed in stage 1 hypertensive patients after quercetin treatment . However , indices of oxidant stress measured in the plasma and urine were not affected by quercetin . These data are the first to our knowledge to show that quercetin supplementation reduces blood pressure in hypertensive subjects . Contrary to animal-based studies , there was no quercetin-evoked reduction in systemic markers of oxidative stress In vitro studies show Hibiscus sabdariffa L. , an ingredient found in many herbal tea blends and other beverages , has antioxidant properties , and , in animal models , extracts of its calyces have demonstrated hypocholesterolemic and antihypertensive properties . Our objective in this study was to examine the antihypertensive effects of H. sabdariffa tisane ( hibiscus tea ) consumption in humans . A r and omized , double-blind , placebo-controlled clinical trial was conducted in 65 pre- and mildly hypertensive adults , age 30 - 70 y , not taking blood pressure (BP)-lowering medications , with either 3 240-mL servings/d of brewed hibiscus tea or placebo beverage for 6 wk . A st and ardized method was used to measure BP at baseline and weekly intervals . At 6 wk , hibiscus tea lowered systolic BP ( SBP ) compared with placebo ( -7.2 + /- 11.4 vs. -1.3 + /- 10.0 mm Hg ; P = 0.030 ) . Diastolic BP was also lower , although this change did not differ from placebo ( -3.1 + /- 7.0 vs. -0.5 + /- 7.5 mm Hg ; P = 0.160 ) . The change in mean arterial pressure was of borderline significance compared with placebo ( -4.5 + /- 7.7 vs. -0.8 + /- 7.4 mm Hg ; P = 0.054 ) . Participants with higher SBP at baseline showed a greater response to hibiscus treatment ( r = -0.421 for SBP change ; P = 0.010 ) . No effects were observed with regard to age , gender , or dietary supplement use . These results suggest daily consumption of hibiscus tea , in an amount readily incorporated into the diet , lowers BP in pre- and mildly hypertensive adults and may prove an effective component of the dietary changes recommended for people with these conditions BACKGROUND To evaluate health benefits attributed to Hibiscus sabdariffa L. a r and omized , open-label , two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract ( HSE ) on the systemic antioxidant potential ( AOP ; assayed by ferric reducing antioxidant power ( FRAP ) ) with a reference treatment ( water ) in eight healthy volunteers . The biokinetic variables were the areas under the curve ( AUC ) of plasma FRAP , ascorbic acid and urate that are above the pre-dose concentration , and the amounts excreted into urine within 24 h ( Ae(0 - 24 ) ) of antioxidants as assayed by FRAP , ascorbic acid , uric acid , malondialdehyde ( biomarker for oxidative stress ) , and hippuric acid ( metabolite and potential biomarker for total polyphenol intake ) . RESULTS HSE caused significantly higher plasma AUC of FRAP , an increase in Ae(0 - 24 ) of FRAP , ascorbic acid and hippuric acid , whereas malondialdehyde excretion was reduced . Furthermore , the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers ' urine ( 0.02 % of the administered dose ) . CONCLUSION The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans . Furthermore , the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols , most likely caused by the colonic microbiota Considering the high prevalence of hypertension , its debilitating end organ damage , and the side effects of chemical drugs used for its treatment , we conducted this experimental study to evaluate the effect of sour tea ( Hibiscus sabdariffa ) on essential hypertension . For this purpose , 31 and 23 patients with moderate essential hypertension were r and omly assigned to an experimental and control group , respectively . Patients with secondary hypertension or those consuming more than two drugs were excluded from the study . Systolic and diastolic blood pressures were measured before and 15 days after the intervention . In the experimental group , 45 % of the patients were male and 55 % were female , and the mean age was 52.6 + /- 7.9 years . In the control group , 30 % of the patients were male , 70 % were female , and the mean age of the patients was 51.5 + /- 10.1 years . Statistical findings showed an 11.2 % lowering of the systolic blood pressure and a 10.7 % decrease of diastolic pressure in the experimental group 12 days after beginning the treatment , as compared with the first day . The difference between the systolic blood pressures of the two groups was significant , as was the difference of the diastolic pressures of the two groups . Three days after stopping the treatment , systolic blood pressure was elevated by 7.9 % , and diastolic pressure was elevated by 5.6 % in the experimental and control groups . This difference between the two groups was also significant . This study proves the public belief and the results of in vitro studies concerning the effects of sour tea on lowering high blood pressure . More extensive studies on this subject are needed Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease . Our previous report suggested that Hibiscus sabdariffa extracts ( HSE ) had a metabolic-regulating and liver-protecting potential . In this study , we performed a clinical trial to further confirm the effect of HSE . Subjects with a BMI ≧ 27 and aged 18 - 65 , were r and omly divided into control ( n = 17 ) and HSE-treated ( n = 19 ) groups , respectively , for 12 weeks . Our data showed that consumption of HSE reduced body weight , BMI , body fat and the waist-to-hip ratio . Serum free fatty acid ( FFA ) was lowered by HSE . Anatomic changes revealed that HSE improved the illness of liver steatosis . Ingestion of HSE was well tolerated and there was no adverse effect during the trial . No alteration was found for serum α-amylase and lipase . The clinical effect should mainly be attributed to the polyphenols of HSE , since composition analysis showed that branched chain-amino acids , which is associated with obesity , is not obviously high . In conclusion , consumption of HSE reduced obesity , abdominal fat , serum FFA and improved liver steatosis . HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver To compare the antihypertensive effectiveness of sour tea ( ST ; Hibiscus sabdariffa ) with black tea ( BT ) infusion in diabetic patients , this double-blind r and omized controlled trial was carried out . Sixty diabetic patients with mild hypertension , without taking antihypertensive or antihyperlipidaemic medicines , were recruited in the study . The patients were r and omly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month . Their blood pressure ( BP ) was measured on days 0 , 15 and 30 of the study . The mean of systolic BP ( SBP ) in the ST group decreased from 134.4±11.8 mm Hg at the beginning of the study to 112.7±5.7 mm Hg after 1 month ( P-value < 0.001 ) , whereas this measure changed from 118.6±14.9 to 127.3±8.7 mm Hg ( P-value=0.002 ) in the BT group during the same period . The intervention had no statistically significant effect on the mean of diastolic BP ( DBP ) in either the ST or BT group . The mean pulse pressure ( PP ) of the patients in the ST group decreased from 52.2±12.2 to 34.5±9.3 mm Hg ( P-value < 0.001 ) during the study , whereas in the BT group , it increased from 41.9±11.7 to 47.3±9.6 mm Hg ( P-value=0.01 ) . In conclusion , consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension . This study supports the results of similar studies in which antihypertensive effects have been shown for ST |
2,186 | 25,084,308 | In terms of antihypertensive medication , no favorable effects of stress-reduction techniques could be identified . | OBJECTIVE A systematic review and meta- analysis focusing on patient-relevant outcomes and blood pressure was conducted to assess the clinical effectiveness of stress-reduction techniques in adults with essential hypertension . | Objective : To examine the efficacy of a new device , which slows and regularises breathing , as a non-pharmacological treatment of hypertension and thus to evaluate the contribution of breathing modulation in the blood pressure ( BP ) reduction . Design and setting : R and omised , double-blind controlled study , carried out in three urban family practice clinics in Israel . Patients : Sixty-five male and female hypertensives , either receiving antihypertensive drug therapy or unmedicated . Four patients dropped out at the beginning of the study .Intervention : Self treatment at home , 10 minutes daily for 8 consecutive weeks , using either the device ( n = 32 ) , which guides the user towards slow and regular breathing using musical sound patterns , or a Walkman , with which patients listened to quiet music ( n = 29 ) . Medication was unchanged 2 months prior to and during the study period . Main outcome measures : Systolic BP , diastolic BP and mean arterial pressure ( MAP ) changes from baseline . Results : BP reduction in the device group was significantly greater than a predetermined ‘ clinical ly meaningful threshold ’ of 10.0 , 5.0 and 6.7 mm Hg for the systolic BP , diastolic BP and MAP respectively ( P = 0.035 , P = 0.0002 and P = 0.001 ) . Treatment with the device reduced systolic BP , diastolic BP and MAP by 15.2 , 10.0 and 11.7 mm Hg respectively , as compared to 11.3 , 5.6 and 7.5 mm Hg ( P = 0.14 , P = 0.008 , P = 0.03 ) with the Walkman . Six months after treatment had stopped , diastolic BP reduction in the device group remained greater than the ‘ threshold ’ ( P < 0.02 ) and also greater than in the walkman group ( P = 0.001 ) . Conclusions : The device was found to be efficacious in reducing high BP during 2 months of self-treatment by patients at home . Breathing pattern modification appears to be an important component in this reduction The purpose of the present study was to test the effectiveness of a cognitive-behavioral intervention as an adjunctive treatment of hypertension . To qualify for the study , subjects had to have an unmedicated clinic diastolic blood pressure > or = 95 mm Hg . After qualification , minimal drug requirements were established using a diuretic and a beta-blocker to control blood pressure at < or = 90 mm Hg . Subjects were then r and omized into a 6-week cognitive-behavioral intervention or a measurements -only control group . After the treatment phase , medication levels were reduced in all subjects by means of a systematic stepdown procedure . Subjects were followed for 1 year after the stepdown was completed . Addition of the cognitive-behavioral intervention was twice as effective as the control procedure in reducing drug requirements . At 12-months follow-up , 73 % of the treatment group were at lower levels of medication than at the time of r and omization , compared to 35 % in the control group . Moreover , 55 % of the treatment group remained completely free of medication , compared to 30 % of the control group , at the 12-month follow-up . The reductions in medication were associated with maintained controlled levels of clinic , ambulatory , and home blood pressure . The addition of a st and ardized and inexpensive group-administered cognitive-behavioral intervention to the drug treatment of hypertension is beneficial as an adjunctive treatment in reducing drug requirements for patients with hypertension , thereby reducing the costs and potential side effects of antihypertensive medications Thirty-three moderate hypertensives were converted to a 2-drug regimen of metoprolol and diuretic and BPs stabilized at a well-controlled level . They then completed one of three conditions over an 8-week interval : ( I ) 16 sessions of TBF ( h and and foot warming ) ; ( II ) 16 sessions of frontal EMG-BF ; ( III ) regular home monitoring of BP . Attempts were then made to withdraw the patients from the sympatholytic medication . Those successfully withdrawn were followed up for one year . There were no significant advantages for TBF over the other two conditions in the short term or with long-term follow-up . Only 27 % of treated patients ( including Condition III failures who were remedicated and treated with TBF ) were successfully off of the sympatholytic at a one-year follow-up . The generally poor results on clinical outcome were confirmed by clinic BPs , home BPs by patients , and 24-hour ambulatory BPs On screening 192 men and women aged 35 - 64 were identified as having two or more of the following risk factors : blood pressure greater than or equal to 140/90 mm Hg , plasma cholesterol concentration greater than or equal to 6.3 mmol/l ( 243.6 mg/100 ml ) , and current smoking habit greater than or equal to 10 cigarettes a day . They were r and omly allocated to a group for modification of behaviour or to serve as controls . Both groups were given health education leaflets containing advice to stop smoking , to reduce animal fats in the diet , and on the importance of reducing blood pressure . In addition , the treatment group had group sessions of one hour a week for eight weeks in which they were taught breathing exercises , relaxation , and meditation and about managing stress . It had previously been found that after eight weeks and eight months there was a significantly greater reduction in both systolic and diastolic blood pressures in the group taught to relax compared with the control group . After four years of follow up these differences in blood pressure were maintained . Plasma cholesterol concentration and the number of cigarettes smoked were lower in the treatment group at eight weeks and eight months but not at the four year follow up . At four years more subjects in the control group reported having had angina and treatment for hypertension and its complications . Incidence of ischaemic heart disease , fatal myocardial infa rct ion , or electrocardiographic evidence of ischaemia was significantly greater in the control group . If the results of this study could be obtained in a larger study the financial and health care implication s would be enormous & NA ; This industry‐based r and omized study compared the effects of behavioral treatment ( BT ) and blood pressure monitoring ( BPM ) on blood pressure ( BP ) change in 158 unmedicated persons with mild hypertension ( diastolic blood pressure 90 to 104 mm Hg ) . Participants recruited by a three‐stage screening were r and omly assigned to BT or BPM groups and stratified by entry diastolic blood pressure ( DBP ) , age , and sex . BT participants received relaxation training , with or without the addition of biofeedback , cognitive restructuring , and health behavior change components . During the study , all participants were followed by their usual care physicians and received medical advice . At 18 weeks into the study , after the BT groups completed training , both the BT and BPM groups showed significant reductions in systolic blood pressure ( SBP ) and DBP assessed in the company medical clinic ( 7.4 and 9.0 mm Hg SBP and 4.5 and 5.9 mm Hg DBP , respectively ) . These reductions were maintained throughout the 36‐week follow‐up period . Reductions in BP assessed at the participants ' worksite were similar for BT and BPM participants throughout most of the trial , indicating little advantage to the inclusion of behavioral interventions over monitoring alone . Differences in BP changes observed among participants receiving various combinations of behavioral treatment components indicated that the cognitive restructuring component reduced SBP in the worksite by an additional 5.4 mm Hg ( p less than 0.05 ) . Possible explanations for the BP changes observed in the BPM group and implication s of the results for the treatment of unmedicated mild hypertensives are discussed The present study compared the effectiveness of three procedures in the treatment of 34 individuals with essential hypertension : ( 1 ) stress management training plus relaxation imagery , which consisted of an adaptation of existing stress management techniques in conjunction with extensive relaxation training using relaxation imagery ; ( 2 ) relaxation imagery alone ; and ( 3 ) weekly blood pressure checks . The relaxation imagery technique involved visualization of a relaxing image along with concentration on suggestions of relaxation , heaviness , and warmth . Treatment was individualized and lasted 8 weeks . Results indicated stress management plus relaxation imagery and relaxation imagery alone were significantly more effective than blood pressure checks in reducing systolic and diastolic blood pressures during treatment and in maintaining diastolic blood pressure reductions during follow-up . However , no significant differences were found between the two treatment procedures . Clinical implication s of these findings are discussed BACKGROUND To our knowledge , no single investigation concerning the long-term effects of overweight status on the risk for hypertension , hypercholesterolemia , diabetes mellitus , and cardiovascular sequelae has been reported . METHODS Relations between categories of body mass index ( BMI ) , cardiovascular disease risk factors , and vascular disease end points were examined prospect ively in Framingham Heart Study participants aged 35 to 75 years , who were followed up to 44 years . The primary outcome was new cardiovascular disease , which included angina pectoris , myocardial infa rct ion , coronary heart disease , or stroke . Analyses compared overweight ( BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 25.0 - 29.9 ) and obese persons ( BMI > or = 30 ) to a referent group of normal-weight persons ( BMI , 18.5 - 24.9 ) . RESULTS The age-adjusted relative risk ( RR ) for new hypertension was highly associated with overweight status ( men : RR , 1.46 ; women : RR , 1.75 ) . New hypercholesterolemia and diabetes mellitus were less highly associated with excess adiposity . The age-adjusted RR ( confidence interval [ CI ] ) for cardiovascular disease was increased among those who were overweight ( men : 1.21 [ 1.05 - 1.40 ] ; women : 1.20 [ 1.03 - 1.41 ] ) and the obese ( men : 1.46 [ 1.20 - 1.77 ] ; women : 1.64 [ 1.37 - 1.98 ] ) . High population attributable risks were related to excess weight ( BMI > or = 25 ) for the outcomes hypertension ( 26 % men ; 28 % women ) , angina pectoris ( 26 % men ; 22 % women ) , and coronary heart disease ( 23 % men ; 15 % women ) . CONCLUSIONS The overweight category is associated with increased relative and population attributable risk for hypertension and cardiovascular sequelae . Interventions to reduce adiposity and avoid excess weight may have large effects on the development of risk factors and cardiovascular disease at an individual and population level Controlled studies have demonstrated that relaxation training can lead to significant in-clinic blood pressure ( BP ) reductions in patients with essential hypertension . We examined the BP-lowering effect of relaxation training during the working day . Forty-two patients being treated for essential hypertension with diastolic BPs greater than 90 mm Hg were r and omized into either a relaxation training program or no treatment . Multiple BP measurements were made during the working hours , using an ambulatory monitoring device , before and after training . Significant work-site differences between groups were evident after treatment both for systolic and diastolic pressures . These results suggest that relaxation therapy leads to a reduction in BP that is evident in the natural environment , providing new evidence that the procedure is a useful adjunct to the treatment of hypertensive patients & NA ; This article reports the findings of a study design ed to evaluate the long‐term effectiveness of an industry‐based relaxation training program in the treatment of hypertensives whose blood pressures were not well controlled by antihypertensive medication . Following a three‐stage screening process , 137 participants were r and omly allocated to either relaxation training ( RT ) or to blood pressure monitoring ( BPM ) at two worksites . Participants continued to receive medical care from their primary physicians during the course of the study . The advantage for participants receiving RT , in terms of mean blood pressure changes , was modest and of short duration . However , a larger proportion of participants in the RT group came into good control ( blood pressures below 90 mm Hg ) than in the BPM group following treatment ( 69.4 % vs 41.5 % , p less than 0.001 ) . This advantage continued to 24 months ' follow‐up ( 63.9 % vs 47.7 % , p less than 0.05 ) . At 30 months ' follow‐up there was no significant difference between the groups ( 75.0 % vs 70.8 % ) . Within‐group analyses revealed that the BPM group also achieved significant blood pressure lowering which was maintained during the study . The largest initial difference between the two groups was for individuals whose entry diastolic blood pressures were most out of control despite several years of pharmacologic treatment . No difference was found between the two groups in the prescription of antihypertensive medication Fifty-two pharmacologically treated hypertensive patients were r and omized to one of four treatment groups : ( 1 ) diastolic blood pressure biofeedback , ( 2 ) progressive deep muscle relaxation training , ( 3 ) self-directed relaxation training , or ( 4 ) medication alone . Data collection occurred during baseline , treatment , and 1-year follow-up phases in a laboratory , a medical clinic , and the patient 's own home . Patients from all four groups combined showed mean blood pressure reductions of −10.2/−5.5 mm Hg on clinic recordings and −2.4/−.7 mm Hg on home recordings , which were maintained throughout the follow-up period . There were no significant differences among the four groups in terms of blood pressure reduction . Patients given adjunctive behavioral treatment showed significantly larger reductions in medication usage compared to patients treated with medication alone , but there were no significant differences among the three behaviorally treated groups . Patients who showed medication reductions did not show subsequent blood pressure elevation . The results suggest that combined behavioral and pharmacological therapy may be superior to pharmacological therapy alone in the treatment of essential hypertension CONTEXT Although psychosocial factors are correlated , previous studies on risk factors for hypertension have typically examined psychosocial factors individually and have yielded inconsistent findings . OBJECTIVE To examine the role of psychosocial factors of time urgency/impatience ( TUI ) , achievement striving/competitiveness ( ASC ) , hostility , depression , and anxiety on long-term risk of hypertension . DESIGN , SETTING , AND STUDY POPULATION : A population -based , prospect i ve , observational study using participant data from the Coronary Artery Risk Development in Young Adults ( CARDIA ) study . A total of 3308 black and white adults aged 18 to 30 years ( when recruited in 1985 and 1986 ) from 4 US metropolitan areas and followed up through 2000 to 2001 . MAIN OUTCOME MEASURES Fifteen-year cumulative incidence of hypertension ( systolic blood pressure of 140 mm Hg or higher , diastolic blood pressure of 90 mm Hg or higher , or taking antihypertensive medication ) . RESULTS The incidence of hypertension at year 15 was 15 % from baseline and 13.6 % from year 5 . After adjusting for the same set of hypertension risk factors and each of the psychosocial factors of TUI , ASC , hostility , depression , and anxiety in 5 separate logistic regression models , higher TUI and hostility were significantly associated with risk of developing hypertension at 15-year follow-up for the total sample . Compared with the lowest score group , the adjusted odds ratio ( OR ) for TUI was 1.51 ( 95 % confidence interval [ CI ] , 1.12 - 2.03 ) for a score of 1 ; 1.47 ( 95 % CI , 1.08 - 2.02 ) for a score of 2 ; and 1.84 ( 95 % CI , 1.29 - 2.62 ) for a score of 3 to 4 ( P for trend = .001 ) . Compared with the lowest quartile group , the adjusted OR for hostility was 1.06 ( 95 % CI , 0.76 - 1.47 ) for quartile 2 ; 1.38 ( 95 % CI , 1.00 - 1.91 ) for quartile 3 ; and 1.84 ( 95 % CI , 1.33 - 2.54 ) for quartile 4 ( P for trend < .001 ) . No consistent patterns were found for ASC , depression , or anxiety . Race- and sex-specific analyses and multivariable models with simultaneous adjustment for all 5 psychosocial factors and other hypertension risk factors had generally similar results . CONCLUSION Among young adults , TUI and hostility were associated with a dose-response increase in the long-term risk of hypertension Thirty-one patients receiving medical treatment for essential hypertension were r and omly distributed into three groups : ( 1 ) relaxation therapy , ( 2 ) nonspecific therapy , and ( 3 ) medical treatment only . The nonspecific therapy group spent the same amount of time with the therapists as the relaxation group but was not given a specific therapy . Blood pressures were measured at a different time and in a different place from the behavioral treatments . The relaxation therapy group showed a significant reduction in blood pressure postreatment compared with the nonspecific therapy and medical treatment only groups , even when those patients whose medication was increased were excluded from the data analysis . At follow-up six months post-treatment , the relaxation group showed a slight decrement in treatment effects , while both the nonspecific therapy and medical treatment only groups showed continued improvement ; thus , there was not a significant difference between groups Ninety patients with essential hypertension were followed for 5 years . Initially the patients were r and omized into two groups : ( a ) an experimental group consisting of 44 patients who received autogenic training and ( b ) a control group of 46 patients who did not receive any behavioral intervention . By the end of the follow-up period , the experimental group was significantly different from the control group , with reduced blood pressure ( by 5.8 mm Hg systolic and 3.2 mm Hg diastolic vs. 4.3 mm Hg systolic and 2.0 mm Hg diastolic ) , a smaller increase in left-ventricular myocardial mass ( 14.6 g vs. 38.2 g ) , improved psychological indices , and a decrease in the number of sick days of leave . Autogenic training appeared to be more effective in patients with mild hypertension than in those with moderate hypertension and the results were comparable with those obtained with regular medication To see whether general practitioners could effectively carry out training in relaxation and management of stress to reduce mild hypertension a study was carried out with a sub sample of phase 2 of the Medical Research Council 's treatment of mild hypertension trial.1 In the main mild hypertension trial patients had been receiving either an active drug or placebo for six years . In phase 2 a sub sample of these patients were r and omly allocated either to continue or to stop receiving the active drug or placebo . In a further sub sample patients were again r and omised to receive or not to receive relaxation therapy . This factorial design presented an additional opportunity to assess whether patients controlled with active drugs might have their blood pressure maintained by this behavioural therapy once drug treatment was stopped and to assess whether blood pressure might be further reduced by this therapy in patients who had been under regular medical supervision for as long as six years and who had already received non-pharmacological advice . The therapy was conducted by general practitioners in group sessions once a week for eight weeks . The training in relaxation was accompanied by galvanic skin resistance biofeedback . At one year follow up blood pressure in the relaxation subgroups was either maintained ( in the group who had stopped receiving drugs ) or reduced further ( in the group who had continued receiving drugs and in both placebo groups ) , while in the control group it had increased in all the subgroups , but particularly in those who had stopped receiving drugs . Differences in changes in blood pressure between the relaxation and control groups were significant . There were five new cardiovascular events , including evidence of myocardial ischaemia in blindly coded electrocardiograms in the control group , compared with one in the treatment group . General practitioners , if motivated , can successfully apply this technique of training those with mild hypertension in relaxation and management of stress Employees of a large industry were screened for the presence of coronary risk factors . A total of 204 employees , aged 35 - 64 years , with two or more such factors ( serum cholesterol concentration greater than or equal to 6.3 mmol/l ( 243.6 mg/100 ml ) , blood pressure greater than or equal to 140/90 mm Hg , and current cigarette consumption greater than or equal to 10 cigarettes a day ) were r and omly allocated to a biofeedback group receiving training in relaxation and management of stress or a control group . Both groups received simple health education literature . After eight weeks of training , and again eight months later , the biofeedback group showed a significantly greater fall in systolic and diastolic blood pressures than the control group ( p less than 0.001 ) . Plasma renin activity and plasma aldosterone concentration were measured in a sub sample at entry to the study and again at eight weeks and eight months ; both showed a greater reduction in the biofeedback compared with the control group at eight weeks ' follow-up . The greater reduction in blood pressure in the subjects in the biofeedback group compared with the control group ( 11.0 mm Hg systolic and 8.8 mm Hg diastolic ) , persisting eight months after the training , suggests that relaxation-based behavioural methods might be offered as a first-time treatment to patients with mild hypertension Background The possibility that daily sessions of music-guided slow breathing may reduce 24-h ambulatory blood pressure ( ABP ) , and predictors of efficacy were explored in a r and omized , placebo-controlled trial with parallel design . Methods Age-matched and sex-matched hypertensive patients were r and omized to music-guided slow breathing exercises ( 4–6 breaths/min ; 1 : 2 ratio of inspiration : expiration duration ) ( Intervention ; n = 29 ) or to control groups who were thought to relax while either listening to slow music ( Control-M ; n = 26 ) or reading a book ( Control-R ; n = 31 ) . At baseline and at follow-up visits ( 1 week and 1 , 3 and 6 months ) , ABP monitoring was performed . Results At mixed model analysis , intervention was associated with a significant reduction of 24-h ( P = 0.001 ) and night-time ( 0100–0600 h ) ( P < 0.0001 ) systolic ABP . The average reduction of systolic 24-h ABP at 6 months was 4.6 mmHg [ confidence limits at 95 % 1.93–7.35 ] and 4.1 mmHg ( 95 % confidence limits 1.59–6.67 ) vs. Control-M and Control-R groups , respectively , ( P < 0.001 for both ) . Antihypertensive treatment was selected as negative predictor of BP reduction at multivariate stepwise analysis . When antihypertensive treatment was inserted as covariate in a generalized linear model , psychological subscales assessed at baseline by the Mental Health Inventory question naire were found to affect systolic blood pressure reduction at 6-month follow-up ( general positive affect P < 0.001 ; emotional ties , P < 0.001 ; loss of behavioral control , P = 0.035 ) . In particular , a level of general positive affect higher than the 75th percentiles was found to be significantly associated with low treatment efficacy ( odds ratio 0.09 ; 95 % confidence limits 0.01–0.93 ) . Conclusion Daily sessions of voluntary music-guided slow breathing significantly reduce 24-h systolic ABP , and psychological predictors of efficacy can be identified |
2,187 | 19,114,702 | CMV infections were not significantly reduced with either polyvalent IVIG or CMV-IVIG .
Interstitial pneumonitis was reduced with polyvalent IVIG in older studies but not in the more recent ones , nor in studies assessing CMV-IVIG .
Because there is no advantage in terms of survival or infection prevention , IVIG does not have a role in HSCT | PURPOSE Because the role of immunoglobulins ( IVIG ) prophylaxis in patients undergoing hematopoietic stem-cell transplantation ( HSCT ) has not been established in terms of survival and infection prevention , we conducted a meta- analysis evaluating these issues . | Polyclonal intravenous IgG ( IVIG ) was administered as an infusion 6 times every 3 weeks ( week 0 , 3 , 6 , 9 , 12 , 15 ) in doses of 0.1 , 0.4 and 0.8 g/kg BW to determine the dose causing an increase in 12 pneumococcal antibody types above the protective level of 200 ng/ml of antibody N. The dose of 0.4 g/kg BW was found to be optimal in patients with chronic lymphocytic leukaemia ( CLL ) . From the first infusion onwards at least 80 % of CLL patients had increases in all 12 antibodies . Five weeks after the last infusion the antibody levels were still elevated in 80 % of patients with CLL . The dose of 0.8 g/kg raised all 12 antibodies in 53 - 73 % of CLL patients when assessment s were made after each infusion . In multiple myeloma ( MM ) patients , 73 - 82 % and 73 - 91 % of patients had increased antibody levels , respectively , before and after the 4th-6th infusions at the 0.8 g/kg dose level . However , in only 45 - 50 % of patients did the antibodies remain increased 2 weeks after the treatment at this dose . The dose of 0.4 g/kg caused antibody increases in only 30 - 50 % of patients when measured before the 4th-6th infusion . Serum IgG increased significantly only in the CLL patients , whereas in the MM patients it was high from the beginning owing to the disease . Therefore , the pneumococcal antibody levels were a better marker for the purpose of dose finding . The dosage recommendation in CLL is 0.4 g/kg every 3 weeks until week 12 , when steady state is reached . The maintenance dose is 0.4 g/kg every 5 weeks . In MM patients , who have a faster elimination rate of antibodies , the recommended loading dose is 0.8 g/kg , followed by 0.4 g/kg every week as a continuous treatment . Treatment with IVIG in CLL and MM was generally well tolerated . Only 25 % of patients experienced minor side-effects , the most frequent being febrile reactions , shivering and headache Patients treated with allogeneic bone marrow transplantation ( BMT ) suffer from a deficient humoral immunity during the post-transplant period . To prevent infections patients may receive prophylactic intravenous immunoglobulin ( IVIG ) therapy from 1 week before to 3 months after BMT . We have studied the effect of IVIG treatment on reconstitution of immunoglobulin repertoires in transplanted patients . Sera obtained from 13 IVIG-treated and 31 non-IVIG-treated patients before and at different time points after BMT , ranging from 3 days to 3 years , and from 18 healthy controls , were analyzed using a quantitative immunoblot system . The average immunoglobulin (Ig)M and IgG reactivity profiles against antigens derived from human liver , muscle and skin as well as Staphylococcus epidermidis protein extracts were similar in both patient groups and in controls . Both IgG and IgM reactivity profiles are , however , less heterogeneous among the individuals in the IVIG-treated patient group . Around 1 year after BMT the heterogeneity of the IgM reactivity profiles against allogeneic protein extracts is much lower in the IVIG-treated group compared to the non-IVIG-treated group and the healthy controls . This effect remains months to years after the IVIG treatment has been completed . Our results suggest that IVIG influences selection of the natural antibody repertoire mediated by the variable (V)-region during reconstitution after BMT To determine whether intravenous immunoglobulin ( IVIg ) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection , chronic graft-vs.-host disease ( GVHD ) , and obliterative bronchiolitis after marrow transplantation , patients were assigned r and omly to receive either IVIg ( 500 mg/kg/month ) or no IVIg prophylaxis . Participants were registered before transplantation , and 250 patients ( 123 IVIg and 127 control ) were evaluable for events after day 100 . The two groups were balanced for age , marrow source , cytomegalovirus ( CMV ) seropositivity , pretransplantation conditioning , and prophylaxis for infection and GVHD . Between days 100 and 365 posttransplantation , the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls ( p = not significant ) . During the same period , the incidence of localized infection was marginally higher in control patients than in IVIg recipients ( 0.44 vs. 0.24 , respectively ; relative risk [ RR ] 1.46 , p < 0.07 ) . Administration of IVIg prophylaxis had no effect on survival , the incidence of obliterative bronchiolitis , severity of airflow obstruction , or the incidence or mortality of chronic GVHD . After discontinuing IVIg prophylaxis at day 360 , subsequent recovery of endogeneous humoral immunity was impaired ( serum IgG1 and IgA levels were significantly lower than controls at day 730 ) , and total infections were less common in the second year in control patients than in former IVIg recipients ( 0.12 vs 0.19 , respectively ; RR 0.61 , p = 0.03 ) . We conclude that in the absence of hypogammaglobulinemia , monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation In a study of 63 allogeneic and autologous bone marrow transplants , patients were r and omized to receive the IgM and IgA enriched intravenous immunoglobulin ( IVIG ) preparation ( Pentaglobin ) . Pentaglobin has been postulated to have anti-endotoxin properties and one of the aims of the study was to measure endotoxin levels in these patients together with the clinical sequelae of infection . The anti-endotoxin effects of Pentaglobin were found to reside in the IgM fraction . Those patients who received Pentaglobin were significantly protected from dying from infection in the first 100 days after the transplant , although it was not actually possible to document bacterial infections as the cause of death in the control patients . Peak endotoxin levels were significantly reduced ( p = 0.02 ) in those patients receiving Pentaglobin . Liver damage as assessed by liver enzyme abnormalities correlated significantly with the presence of endotoxaemia greater than 25 pg/ml and up to 70 % of pyrexial episodes were associated with endotoxaemia . Our results suggest that Pentaglobin is useful in reducing hepatic toxicity and this may be related to a reduction in endotoxaemia Overwhelming infections cause significant morbidity and mortality in the immunocompromised host . There is considerable in vitro and in vivo evidence that the immune deficient state which accompanies acute leukaemia , and , is exacerbated by intensive chemotherapy , contributes to the infection risk in these patients . The most easily documented and corrected is that of impaired humoral immunity . In order to study the clinical significance of the deficit a double blind , r and omised , placebo controlled pilot study was set up design ed to test the feasibility , efficacy and toxicity of using prophylactic intravenous immunoglobulin to prevent infective complications in this patient group . Patients received 150 mg/kg of Pentaglobin , an immunoglobulin preparation specifically enriched in IgM and IgA , on days 0 , 10 and 20 of the chemotherapy regimes . There were no adverse side effects . Patients in the placebo group had a 25 % fall in IgM level whilst IgG and IgA remained unchanged . The treatment group maintained a stable IgM and IgG concentration throughout but had a rise in IgA. There was no difference in the total number of septicaemic episodes in each group but the placebo group had an increased number of non Staphylococcal infections ( P < 0.04 ) . We conclude that intravenous Pentaglobin protects patients against a fall in IgM during induction chemotherapy for acute leukaemia and decreases the number of non Staphylococcal infections A r and omized crossover study of prophylactic immunoglobulin ( IgG ) therapy was performed in patients with chronic lymphocytic leukaemia ( CLL ) or non-Hodgkin 's lymphoma ( NHL ) . Twelve patients with hypogammaglobulinemia or a history of recurrent infections received infusions of IgG or placebo intravenously ( IV ) every 3 weeks for 1 year . They were then switched to the alternative preparation for another year . The number of serious bacterial infections was significantly less ( P = .001 ; Mainl and 's cross-over method ) in the months in which patients received IgG. Serious bacterial infections showed a trend to be associated with an IgG level less than 6.4 g/L ( P = .046 ; Fisher 's exact test ) Forty-two patients with chronic lymphocytic leukaemia ( CLL ) , serum IgG levels < 5.5 milligrams and a history of two or more recent infections , were r and omized to receive infusions of 18 g human intravenous immunoglobulin ( IVIg ) or human albumin placebo every three weeks . During the 12 month study 122 infections were documented but only four were associated with neutropenia . Ten patients ( 24 % ) with IgG levels < 3.0 milligrams experienced 65 % of the infections . In response to IVIg there were immediate and accumulative increases in serum IgG levels and an associated decrease in total and serious infections . If three further infections occurred , placebo patients were commenced on 18 g IVIg , and IVIg patients were increased to 24 g IVIg . Approximately 50 % of these cases subsequently remained infection free . The study shows the usefulness of prophylactic S and oglobulin in CLL patients with hypogammaglobulinaemia , and suggests that this may be justified in those with recurrent infections and serum IgG levels < 3 milligrams Treatment with intense myelosuppressive therapy ( including bone marrow transplantation ) has improved survival in patients with various malignant neoplasms [ 1 , 2 ] . Unfortunately , this treatment increases the incidence of infectious complications , primarily during the period of myelosuppression [ 3 ] . Various methods have been used to limit infection during myelosuppression [ 4 - 7 ] . Despite these pre caution s , bacteremia and fungemia continue to occur in at least one third of patients with sustained neutropenia . Intravenous immunoglobulin ( IVIG ) therapy prevents infections in patients with inborn B-cell deficiencies and hypogammaglobulinemia secondary to hematologic disorders such as chronic lymphocytic leukemia [ 8 - 10 ] . Intravenous immunoglobulin has also been used successfully to treat immune thrombocytopenic purpura , alloimmunity to platelets , and other immune-mediated disorders by a mechanism of immune system modulation [ 11 ] . After allogeneic bone marrow transplantation , IVIG is commonly used to prevent graft-versus-host disease [ 12 ] . During these bone marrow transplant trials , a reduction in bacterial infection was also observed in patients who were not necessarily hypogammaglobulinemic . This finding was initially reported in small anecdotal series but was later confirmed by large prospect i ve studies [ 12 - 17 ] . This effect of IVIG was observed during the pre-engraftment ( neutropenic ) and myelosuppression recovery phases . Most patients in these studies were undergoing allogeneic bone marrow transplantation , for which graft-versus-host disease and its treatment contribute to the rate of infection [ 18 ] . Intravenous immunoglobulin is not routinely used during autologous bone marrow transplantation or severely myelosuppressive therapy because prevention of graft-versus-host disease is unnecessary . Because IVIG prevents infection after allogeneic bone marrow transplantation , it might also do so in other patients undergoing intense myelosuppression and thus may serve as a general prophylactic agent for infections . Intravenous immunoglobulin is expensive and thus should not be used indiscriminately . We design ed a prospect i ve study that r and omized patients who were expected to develop severe and sustained myelosuppression to receive IVIG or no treatment . We specifically wished to determine whether IVIG could reduce the incidence of severe infections in patients with neutropenia but without allogeneic cofactors such as graft-versus-host disease . We therefore sought to determine whether the benefits of IVIG after allogeneic bone marrow transplantation occur as a direct effect of the drug or as an indirect result of a reduced incidence of graft-versus-host disease . Methods Study Design We conducted a stratified , r and omized comparison of patients who either underwent autologous bone marrow transplantation or received substantial myelosuppressive therapy for acute leukemia or other malignant conditions . The protocol and consent forms were approved by the Institutional Review Boards of the three participating institutions : Baylor University Medical Center , Dallas , Texas ; The University of Louisville , Louisville , Kentucky ; and V and erbilt University , Nashville , Tennessee . Patients were stratified for treatment ( autologous bone marrow transplantation or myelosuppressive therapy ) and were r and omized at each study center by a computer-generated scheme to receive IVIG or no treatment . Neither tumor-specific cytoreductive therapy nor state of disease were used as strata . Patients with an ongoing infection , those younger than 17 years , and those with a previous intolerance to IVIG were ineligible for the study . The main end points were the development of proven clinical infection , positive blood cultures for bacteria or fungi , and survival until hospital discharge . Other analyses included the number of platelet transfusions and the development of clinical alloimmunity to platelet transfusion . Patients Between February 1990 and December 1991 , 170 patients entered the study . All patients were evaluable for efficacy and were included in the analysis . The distribution of study patients is shown in ( Table 1 ) . The duration of neutropenia , the most important determinant for infection , was similar between the two groups ( P > 0.2 ) . Patients in the treatment arm and those in the control arm had statistically similar distributions of overall cytotoxic regimens and disease diagnoses ( data not shown ) . Table 1 . Patient Characteristics Treatment Protocol The IVIG used ( S and oglobulin , S and oz Pharmaceuticals , East Hanover , New Jersey ) was commercially purchased , reconstituted as a 5 % solution , and administered intravenously at an initial rate of 0.02 mL/kg per minute for 30 minutes and , if tolerated , was increased every 30 minutes to a maximum rate of 0.08 mL/kg per minute . Administration of IVIG was not blinded , and controls received no placebo . Immunoglobulin was given at a weekly dose of 500 mg/kg beginning at the start of cytotoxic treatment . It was discontinued when severe side-effects occurred or when neutropenia resolved ( as defined by a neutrophil count of more than 500 109/L [ 500/L ] for 1 day ) . Supportive Care The patients were hospitalized in HEPA-filtered single rooms , observed strict h and -washing rules , and received low-bacterial diets . Prophylactic oral antibacterial agents were allowed , but prophylactic parenteral antibacterial drugs were not . Patients who were seropositive for Herpes simplex virus received prophylactic acyclovir . All administered blood products were leukofiltered , and patients undergoing autologous bone marrow transplantation also received irradiated blood products . During periods of neutropenia , patients with fever greater than 38 C had two blood cultures taken and received empiric broad-spectrum antibacterial therapy as determined by the study center . Patients whose fever persisted were recultured . If fever persisted for 3 days and no bacterial cause was found , amphotericin B was administered at a dose of 0.5 mg/kg per day . Definitions and Evaluation of Infection The duration of neutropenia was defined as the interval from the first day the absolute neutrophil count decreased below 500 109/L ( 500/L ) until the first day the count exceeded 500 109/L ( 500/L ) . In patients with neutropenia , the interval was measured from the first day of cytotoxic therapy until recovery from neutropenia . Each platelet transfusion , whether with single-donor platelets or r and om-donor pooled platelets , was denoted as one episode . Clinical alloimmunity was diagnosed when platelet counts measured 1 hour after transfusion increased by less than 5000 109/L ( < 5000/L ) per unit of r and om- or single-donor platelets transfused on two consecutive occasions . The diagnosis of bacteremia and fungemia required one or more positive blood cultures in patients with suspected infection . The diagnosis of clinical infection required evidence of a localized tissue infection with supporting features such as fever , chills , pain , or erythema with or without isolation of a pathogen . Fever without localized evidence of infection or without positive blood cultures was not considered to represent clinical infection . Statistical Analysis Assuming an infection rate of 40 % , the study was design ed to detect an anticipated decrease to 20 % with a power of 0.80 and an -error of 0.05 . Results were analyzed according to the intention to treat . For comparisons of patient groups , the Pearson chi-square test or the Mann-Whitney rank-sum test were used . The Pearson chi-square test with confirmation by the confidence interval method of Simon was used to evaluate study end points [ 19 ] . Confidence intervals of 95 % were used . Binary logistic regression was used to evaluate the influence of various clinical and laboratory parameters on the end points of bacteremia or fungemia . These parameters included age , diagnosis , study center , duration of neutropenia , baseline IgG value , use of prophylactic oral antibacterials , and use of IVIG . To evaluate hypogammaglobulinemia , 5 g/L ( 500 mg/dL ) was chosen as the lower limit of normal . To evaluate the duration of neutropenia , a threshold of 7 days was chosen . The trial ended with the resolution of neutropenia because this patient population rarely experiences serious infections after leukocyte recovery and because survival after hematopoietic recovery is largely determined by the underlying disease . Survival was reported using actual proportions . Results Infections Proven clinical infections were frequent , as shown in Table 2 . Of all study patients , 43.5 % had documented clinical infections . Bacteremia and fungemia occurred in 35 % and 7.6 % of patients , respectively . The incidences of proven clinical infection , bacteremia , and fungemia were 43 % , 35 % , and 6 % in the IVIG group and 44 % , 34 % , and 9 % in the control group , respectively . These differences were not statistically significant ( P > 0.2 ) . Analysis of bacteremia by organism ( gram positive , gram negative , and mixed ) showed no statistical difference . The most common infection in the study was bacteremia due to coagulase-negative Staphylococci . This organism was isolated in 58 % of all cases of bacteremia and was the sole organism in 38 % of all cases of bacteremia . Twenty-eight percent of the documented bloodstream infections were polymicrobial . Table 2 . Treatment Results Only 8 % of patients in this study had hypogammaglobulinemia . The distribution of these patients was similar in the IVIG ( 9 % ) and control ( 8 % ) groups . In multiple regression analysis , the pretreatment value of IgG ( < 5 g/L [ 500 mg/dL ] compared with > 5 g/L ) did not predict the development of bacteremia or fungemia . Bloodstream infections were frequent , but most were controlled by broad-spectrum antibiotics . Death from infection occurred in 3.5 % of study patients ( 4.9 % in the IVIG group compared with 2.3 % in the control group ) , yielding a difference of 2.6 % ( 95 % CI , 3.0 % to 8.2 % ; P > 0.2 ) . Platelet Transfusion Patients in the IVIG BACKGROUND In a recently reported study , low doses of intravenous immunoglobulins ( IVIG ) were shown to be as effective as high doses in protecting chronic lymphocytic leukemia ( CLL ) patients against infections , although a control group was not included . With this background we started a crossover study of low-dose IVIG prophylaxis aim ed at investigating its superiority over empirical treatment of infections . MATERIAL S AND METHODS Forty-two CLL patients with hypogammaglobulinemia ( IgG < 600 mg/dL ) and /or a history of at least one episode of severe infection in the 6 months preceding inclusion in the study were r and omly allocated to receive either an infusion of 300 mg/kg IVIG every 4 weeks for 6 months or no treatment . Then they were switched to observation or IVIG for another 12 months ; finally , they received IVIG or no therapy for 6 more months . RESULTS A significantly lower incidence of infectious episodes was observed during IVIG prophylaxis in 30 patients who completed the 6-month period of either observation or IVIG therapy . The same applied to the 17 patients who completed 12 months of either observation or IVIG prophylaxis . Interestingly , the restoration of serum IgG levels obtained in 17 out of 25 patients ( mean percent value of IgG increase , 41.8 % ) did not parallel a decrease in the number of infectious episodes . CONCLUSIONS A protective effect against infections is demonstrated for low-dose IVIG in the present study . A benefit was shown in patients who completed either 12 or 6 months of IVIG prophylaxis ; however , even this low-dose treatment is not a cost effective way to prevent infection in CLL patients Endotoxin was measured in over 1000 plasma sample s from bone marrow transplant patients in a r and omized trial of the IgM-enriched intravenous immunoglobulin ( IVIG ) Pentaglobin . Peak endotoxaemia was significantly reduced ( P = 0.02 ) in patients receiving Pentaglobin and 70 % of all pyrexias of unknown origin were associated with endotoxaemia . Gut mucosal damage , assessed by lactulose/mannitol ratios , was significantly associated ( P = 0.02 ) with endotoxaemia . Specific IgM antibody to endotoxin core-glycolipid was significantly raised ( P < 0.01 ) in patients receiving the IVIG , and the IgM fraction of Pentaglobin was found to contain most of the anti-endotoxin antibody activity of the IVIG . These results suggest a role for IgM-enriched IVIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant patients The effects of prophylactic , polyvalent intravenous immune globulin on cytomegalovirus infection and interstitial pneumonia in allogenic marrow transplants were evaluated in an ongoing , r and omized controlled trial . Thirty-eight patients were given weekly doses ( 20 cc/kg ) of polyvalent intravenous immune globulin before and after transplantation , and 37 patients were controls . Both symptomatic cytomegalovirus infection ( 17 of 37 or 46 % vs. 8 of 38 or 21 % , p = 0.04 ) and interstitial pneumonia ( 17 of 37 or 46 % vs. 7 of 38 or 18 % , p = 0.02 ) occurred less frequently in the recipients of polyvalent intravenous immune globulin . In separate kinetic studies , a 5 cc/kg dose of a cytomegalovirus-specific hyperimmune globulin produced cytomegalovirus antibody titers in patients equivalent to those achieved after the 20 cc/kg dose of polyvalent intravenous immune globulin . All immune globulin preparations were well-tolerated . These preliminary results suggest that intravenous immune globulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in marrow transplants . Additional trials are now needed to define the minimal effective dose of intravenous immune globulin and to compare the effectiveness of different intravenous immune globulin formulations The most common complication of chronic lymphocytic leukaemia ( CLL ) is infection , which occurs mainly in advanced stages of disease or in those patients with hypogammaglobulinaemia . Intravenous immune globulin ( IVIG ) has been shown to be a useful prophylactic therapy against infections in such patients . A r and omized , double-blind study on 36 patients receiving either 500 mg/kg or 250 mg/kg IVIG every 4 weeks was undertaken to determine the dose regimen required . There was no significant difference in the two treatment groups and we found that CLL patients were equally protected with low-dose IVIG Context No placebo-controlled trials have evaluated potential benefits of immunoglobulin in patients undergoing hematopoietic stem-cell transplantation . Contribution This multicenter r and omized , double-blind trial involved 200 recipients of HLA-matched sibling transplants . At 6 months , the benefit of prophylactic immunoglobulin ( given weekly from day 7 to day 100 ) compared with placebo was not significant for the following outcomes : number of infections , interstitial pneumonia , graft-versus-host disease , and transplantation-related mortality . Implication s Prophylactic immunoglobulin is not indicated for patients undergoing allogeneic hematopoietic stem-cell transplantation from HLA-identical siblings . The Editors Despite controversy about the benefit of immunoglobulin in stem-cell transplantation , this agent has been given as part of most transplantation protocol s for more than 20 years . Several large controlled series showed that immunoglobulin prevented infection ( 1 , 2 ) , especially cytomegalovirus infection ( 3 ) , interstitial pneumonia ( 3 , 4 ) , and graft-versus-host disease ( 2 , 3 , 5 ) ; patients older than 20 years of age experienced the most benefit ( 1 , 6 ) . However , because of different products ( hyperimmune or polyvalent immunoglobulins ) , schedules , dosing regimens , and patient sample s , it has been difficult to definitively conclude that immunoglobulin is beneficial for transplant recipients . The varying conclusions of two large meta-analyses ( 6 , 7 ) have encouraged new trials to better define the optimal dose and duration of immunoglobulin therapy and its value . Immunoglobulin exposes patients to the potential transmission of new pathogens . It is very expensive in high doses and is not always well tolerated . Although immunoglobulin is still widely used , strong evidence supporting its use is lacking . None of the early trials , which led to the approval of immunoglobulin in most countries , were placebo controlled , and two recent trials comparing doses did not include a control group ( 8 , 9 ) . In addition , effective agents are now available to prevent and treat most of the infections that led to the original use of prophylactic immunoglobulin . To re-evaluate the benefit of immunoglobulin in allogeneic stem-cell transplantation using current protocol s , we conducted a r and omized , double-blind , dose effect , placebo-controlled study limited to recipients of transplants from an HLA-identical sibling . To our knowledge , this is the first placebo-controlled study evaluating immunoglobulin in this population . We assessed the value of immunoglobulin , given from day 7 to day 100 , in the prophylaxis of transplantation-related complications . Methods Study Design We design ed the study as a multi-institutional trial involving 19 centers of the Socit Franaise de Greffe de Molle in France ( Figure 1 ) . Patients were recruited at a visit 14 to 28 days before transplantation . They were r and omly assigned to receive 16 weekly doses , from day 7 to day 100 , of placebo ( group 1 ) or polyvalent immunoglobulin at 50 mg/kg of body weight ( group 2 ) , 250 mg/kg ( group 3 ) , or 500 mg/kg ( group 4 ) ; the proportion of patients in each group was equal . Day 0 was the day of transplantation . R and omization was central ized ; stratified by center , age , and disease status ; and performed 14 to 28 days before transplantation . The ethical committee of Hpital Piti-Salptrire , Paris , approved the protocol , and all patients gave informed consent . Data were collected prospect ively and verified on site with the original charts . Figure 1 . Flow diagram of the trial . R and omization We used a r and omization procedure with r and om permuted blocks to ensure the same number of patients at certain equally spaced points in the sequence of patient assignments in each center . The physicians responsible for recruitment in each center did not know the block size . Each sequence was computer generated . Eligibility Criteria We used the following inclusion criteria : age older than 2 years , first-time recipient of an allogeneic stem-cell transplant from an HLA-identical sibling , and no plans for T-cell depletion . Exclusion criteria were as follows : a syngeneic , unrelated , or haplo-mismatched donor ; nonmyeloablative conditioning ; previous autologous transplants conditioned with total-body irradiation or busulfan and cyclophosphamide ; active infection ; presence of hypogammaglobulinemia ( < 4 g/L ) at time of r and omization ; or presence of HIV . Immunoglobulin and Placebo Administration Immunoglobulin was provided from unselected , commercially available lots [ S and oglobulin , Novartis Pharma , Rueil-Malmaison ] . The placebo was a 5 % dextrose solution . We maintained blinding during the study by using two procedures : 1 ) The immunoglobulin was prepared by the pharmacist and delivered to the clinical unit in bottles with special plastic covers [ a small vertical slit allowed the nurse to watch the level of infusion without seeing the bubbles of the immunoglobulin infusion ] and 2 ) the final volume and flow rate of each infusion were adapted , according to manufacturer recommendations , to the highest immunoglobulin dose ( 500 mg/kg ) . The recommended flow rate was 0.5 mL/kg per hour during the initial 30 minutes of administration , and then , if tolerated , 4 mL/kg per hour . End Points The principal end point was the cumulative incidence of infection during the 6 months after transplantation . Secondary end points were time to first infection , occurrence and severity of acute or chronic graft-versus-host disease , occurrence and grade of veno-occlusive disease , interstitial pneumonia , treatment-related mortality at 6 months , overall survival at 2 years , and side effects . Concomitant Treatment , Anti-Infectious Prophylaxis , and Supportive Care All patients received prophylaxis against graft-versus-host disease with methotrexate ( 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6 ) and cyclosporine ( 2 mg/kg per day from the day before transplantation ) to at least day 100 . No patient received prophylactic steroids . All patients were housed in high-efficiency particulate air-filtered or laminar airflow rooms . Intestinal decontamination , according to French practice s , was performed with nonabsorbable antibiotics ( mostly oral colimycin and gentamicin ) and antifungal drugs ( oral polyenes ) during the neutropenic phase . Prophylactic acyclovir was allowed if all patients included in a given center received the same prophylactic strategy . All patients received leukodepleted and irradiated blood products and Pneumocystis carinii prophylaxis until at least day 100 . Patients did not receive prophylactic growth factors or anticytomegalovirus drugs . All patients , except those who were seronegative for cytomegalovirus with seronegative donors , were screened weekly for cytomegalovirus ( using pp65 antigenemia detection or polymerase chain reaction ) until day 100 . Preemptive treatment with ganciclovir or foscarnet for at least 14 days was begun on the basis of one positive test result for pp65 antigenemia or two consecutive positive polymerase chain reaction results within 7 days . Definitions Acute graft-versus-host disease was diagnosed and grade d ( from 0 to IV ) , according to st and ard criteria , on the presence and severity of skin , liver , and intestinal tract injury ( 10 ) . Chronic graft-versus-host disease was grade d as absent , limited , or extensive according to the criteria of Shulman and colleagues ( 11 ) . Veno-occlusive disease was diagnosed by different criteria depending on whether it occurred before or after day 20 ; the criteria were those of Shulman and colleagues ( 12 ) . Criteria for veno-occlusive disease occurring before day 20 were the presence of at least two of the three following manifestations : serum bilirubin level of 34.2 mol/L or greater ( 2.0 mg/dL ) , painful hepatomegaly , or abrupt weight gain of 5 % or more above baseline body weight . Criteria for veno-occlusive disease occurring after day 20 were based on histologic evidence obtained at liver biopsy . The severity of veno-occlusive disease was also grade d : grade 1 , spontaneous resolution of liver symptoms ; grade 2 ( moderate ) , resolution of symptoms with specific treatments ; or grade 3 ( severe ) , no resolution before day 100 or death , whichever occurred first ( 12 ) . Cytomegalovirus infection and disease were defined according to the criteria of the Multidisciplinary International Workshop ( 13 ) . Bacteremia was defined by fever associated with at least one positive blood culture , except for coagulase-negative staphylococci , for which two positive blood cultures from two different sites were required . The diagnosis of bacterial pneumonia required 103 or more colony-forming units/mL in a protected bronchial sample or 104 or more colony-forming units/mL in bronchoalveolar lavage fluid . A definitive diagnosis of Aspergillus pneumonia was made if Aspergillus species were isolated from bronchoalveolar lavage fluid or from a lung biopsy specimen ; the diagnosis was considered probable if an air-crescent sign or characteristic fungus ball was present or results of a serum galactomannane test were positive . Interstitial pneumonia was defined by the presence of nonbacterial , nonfungal pneumonitis and hypoxemia of 75 mm Hg or less while breathing room air . If no cause of infection was identified on at least one bronchoalveolar lavage or lung biopsy ( which included stains for P. carinii and viral tests ) , the diagnosis was idiopathic pneumonia . The severity of infection was grade d as follows : Grade 1 infections were all episodes treated at home or all episodes of fever of unknown origin in neutropenic patients receiving broad-spectrum antibiotics ; grade 3 infections had an expected death rate greater than 60 % ( based on data in the literature ) and included infections associated with Aspergillus , fungemia , and cytomegalovirus disease and any type of pneumonia with a Pao 2 less than 65 mm Hg ; and grade 2 infections were all others ( usually requiring treatment in a hematology ward ) . One author , BACKGROUND AND OBJECTIVE The role of high dose intravenous IgG ( HDIgG ) and of hyperimmune CMV IgG ( CMV-IgG ) in patients undergoing allogeneic hemopoietic stem cell transplantation ( HSCT ) is still unclear . The aim of this study was to compare prophylactic CMV-IgG with HDIgGin a r and omized prospect i ve trial in allogeneic HSCT recipients : primary end point of the study was the occurrence of post-transplant CMV antigenemia ( CMVAg-emia ) . Secondary end-points were severity of acute and chronic graft-versus-host disease ( GvHD ) , infections and transplant related mortality ( TRM ) . DESIGN AND METHODS Patients were r and omized to receive 100 mg/kg/week of CMV-IgG ( group A ; n = 64 ) or 400 mg/kg/week of HDIgG ( group B ; n = 64 ) from day -7 to day + 100 . The two groups were comparable for age , diagnosis , disease status , and acute graft-versus host ( aGvHD ) prophylaxis . RESULTS The actuarial risk at 1 year of CMV antigenemia was lower for CMV-IgG ( 61 % vs. 71 % ) but not significantly ( p = 0.37 ) ; CMVAg-emia occurred at the same interval from HSCT ( 47 vs. 48 days , p = 0.9 ) , with a comparable number of CMVAg positive cells ( 3 vs. 3 p = 0.9 ) . Eight patients died of interstitial pneumonia ( IP ) ( 4 in each group ) , two in group A of CMV-IP . Acute GvHD was scored as O-I , II and III-IV in 39 vs. 35 , 23 vs. 22 and 2 vs. 7 patients respectively for the two groups ( p = not significant ) . The actuarial risk of developing acute GvHD grade II-IV was lower for CMV-IgG ( 39 % vs. 45 % ) but not significantly ( p = 0.43 ) . Chronic GvHD scored as absent in 7 vs. 10 patients , limited in 39 vs. 37 and extensive in 19 vs. 17 patients respectively ( p = not significant ) . Numbered days with intravenous antibiotics , days in hospital , days of fever , number of local and disseminated infections , number of patients with fever of unknown origin were not significantly different . Actuarial 1 year TRM is 18 % vs. 19 % , respectively ( p = 0.9 ) . INTERPRETATION AND CONCLUSIONS This study confirms that CMV antigenemia is comparable in recipients of hyperimmune CMV-IgG and of polyvalent HDIgG , although the former had a 32 % lower cost . It also shows that the potential immunomodulating effect on acute GvHD and transplant mortality is similar with 100 or 400 mg of IgG/kg/week : this is relevant , in view of the high cost of prophylactic In a r and omised study the efficacy of a cytomegalic hyperimmune globulin preparation ( CMV-HIGP ) which had been treated with beta-propiolactone was analysed . The study included 85 patients with acute lymphoblastic leukemia ( ALL ) and Non-B-Non-Hodgkin-lymphoma ( NHL ) who were treated initially or underwent a relapse therapy . During the intense chemotherapeutical period within leukemia treatment the patients were passively immunised by the intravenous route with CMV-HIGP ( 1 ml per kilogram of body weight ) every two to three weeks at the latest . In the initial stages the basic immunisation protection was achieved by the application of double dose CMV-HIGP . The Frankfurt patients were recruited from the BFM-ALL- and the NHL- study since october 1982 . When they were admitted their CMV serostatus was determined by means of the ELA-ELISA or IFA- method . Seronegative patients were given the passive immunisation immediately or 48 hours after the first blood transfusions at the latest . The patients who had become CMV-IgG-positive by passive immunisation were r and omised when reaching long-term therapy according to the protocol . Because of a 30 % cytomegaly disease incidence rate in our patient population a r and omisation was unwarrantable at the beginning of leukemia treatment . During r and omisation one group of patients were immunised by the intravenous route with CMV-HIGP ( 2 ml per kg body weight one time in four weeks ) , the second group was a control group . ( ABSTRACT TRUNCATED AT 250 WORDS Between May 1987 and September 1989 , 72 patients undergoing marrow transplantation at a single institution were r and omized to receive 50 mg/kg of a commercial gammaglobulin preparation or placebo daily in four divided doses for 28 days following transplantation . Patients receiving oral gammaglobulin had significantly increased concentrations of stool IgG ( p = 0.01 ) compared with the placebo group . There was no difference in the amount of diarrhea , frequency of GVHD , duration of hospitalization or survival in the two groups . The present study demonstrates that orally administered IgG can survive passage through the gastrointestinal tract of bone marrow transplantation recipients but there was no effect of oral administration of immunoglobulin on morbidity or mortality following bone marrow transplantation The effects of immune globulin intravenous , 5 percent in 10 percent maltose , on cytomegalovirus infection and interstitial pneumonia in bone marrow transplants were evaluated in a r and omized controlled trial . Eighteen patients were given weekly doses ( 20 cc/kg ) of intravenous immunoglobulin before and after transplantation , and 18 patients were controls . The incidence of cytomegalovirus infection was similar in the control and intravenous immunoglobulin-treated groups , but symptomatic cytomegalovirus infection ( eight of 18 versus three of 18 , p = 0.14 ) and interstitial pneumonia ( 10 of 18 versus four of 18 , p = 0.08 ) occurred less frequently in the group receiving intravenous immunoglobulin . Cytomegalovirus pneumonia developed in eight control patients and in three patients receiving intravenous immunoglobulin ( p = 0.14 ) , whereas two control patients and one patient receiving intravenous immunoglobulin experienced idiopathic interstitial pneumonia . These preliminary results suggest that intravenous immunoglobulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in bone marrow transplant recipients In an attempt to prevent primary cytomegalovirus infection after marrow transplantation , we r and omly assigned 97 patients who were seronegative for antibody to cytomegalovirus before transplantation to receive one of the following : ( 1 ) both intravenous cytomegalovirus immune globulin and seronegative blood products ( 23 patients ) ; ( 2 ) seronegative blood products alone ( 28 patients ) ; ( 3 ) globulin alone ( 22 patients ) ; or ( 4 ) neither treatment ( 24 patients ) . Patients not assigned to receive seronegative blood products received unscreened blood products from r and om donors . The incidence of cytomegalovirus infection according to study group among patients in the study for at least 62 days was 5 percent , 13 percent , 24 percent , and 40 percent , respectively . Among 57 patients with seronegative marrow donors , those who received seronegative blood products had significantly less infection ( 1 of 32 ) than those who received st and ard blood products ( 8 of 25 , P less than 0.007 ) . In contrast , the use of seronegative blood products did not appear to prevent cytomegalovirus infection among patients with seropositive marrow donors . The possibility that cytomegalovirus immune globulin as used in this study can prevent cytomegalovirus infection or ameliorate cytomegalovirus disease was not confirmed , and it can not be recommended for routine use without additional study Intravenous immunoglobulin is approved for use in allogeneic bone marrow transplant recipients for prevention of graft-versus-host disease ( GVHD ) and infections , but the minimally effective dose has not been established . In this multicenter , r and omized , double-blind trial , patients undergoing allogeneic marrow transplantation were r and omized to receive 100 mg/kg , 250 mg/kg , or 500 mg/kg doses of intravenous immunoglobulin . Each dose was given weekly for 90 days and then monthly until 1 year after transplant . Six hundred and eighteen patients were evaluated . Acute GVHD ( grade s 2–4 ) occurred in 39 % of the patients ( 80 of 206 ) in the 100 mg/kg group , 42 % of the patients ( 88 of 208 ) in the 250 mg/kg group , and in 35 % of the patients ( 72 of 204 ) in the 500 mg/kg group ( P = 0.344 ) . Among patients with unrelated marrow donors , a higher dose of intravenous immunoglobulin ( 500 mg/kg ) was associated with less acute GVHD ( P = 0.07 ) . The incidences of chronic GVHD , infection and interstitial pneumonia were similar for all three doses of intravenous immunoglobulin . The dose of intravenous immunoglobulin also had no effect on the types of infection , relapse of hematological malignancy or survival . Except for more frequent chills ( P = 0.007 ) and headaches ( P = 0.015 ) in patients given the 500 mg/kg or 250 mg/kg dose of immunoglobulin , adverse events were similar for all three doses . These results suggest that 100 mg/kg , 250 mg/kg , and 500 mg/kg doses of intravenous immunoglobulin are associated with similar incidences of GVHD and infections in most allogeneic marrow transplants . These results should be considered when design ing cost-effective strategies for the use of intravenous immunoglobulin in allogeneic marrow transplants receiving other current regimens for prophylaxis of GVHD and infection . Bone Marrow Transplantation ( 2001 ) 28 , 187–196 60 children with acute lymphoblastic leukemia were sequentially r and omized at the time of diagnosis : Immunoglobulin ( Endobulin , Immuno ) was administered intravenously to 30 patients at a dose 100 mg/kg/week during the first 3 months , followed by 2 x 200 mg/kg/month immunoglobulin during the 4 . , 5 . , 6 . months . No immunoglobulin was administered to the control patients . We studied the effect of immunoglobulin prophylaxis on the number of days with fever , number of cases with bacteriologically proved infections , length and frequency of antibiotic therapy . Our data confirm the efficacy of immunoglobulin prophylaxis during the intensive phase of leukemia therapy in children The effects of high doses of polyvalent intravenous immune globulin given for prophylaxis of cytomegalovirus infection and interstitial pneumonia in recipients of allogeneic marrow transplants were evaluated in a r and omized controlled trial . Both symptomatic cytomegalovirus infection ( 21 % compared with 46 % , p = 0.03 ) and interstitial pneumonia ( 18 % compared with 46 % , p = 0.02 ) occurred less frequently in the recipients of intravenous immune globulin than in control patients . Prophylactic intravenous immune globulin was also associated with a lower incidence of graft-versus-host disease ( 34 % in recipients compared with 65 % in controls , p = 0.01 ) , but its reduction in rates of interstitial pneumonia was independent of graft-versus-host disease and occurred in both patients with and without graft-versus-host disease . The high doses of immune globulin were well tolerated . Prophylactic intravenous immune globulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia and possibly graft-versus-host disease in patients having allogeneic marrow transplantation BACKGROUND Graft-versus-host disease ( GVHD ) and infection are major complications of allogeneic bone marrow transplantation . Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders , we studied its antimicrobial and immunomodulatory role after marrow transplantation . METHODS In a r and omized trial of 382 patients , transplant recipients given immunoglobulin ( 500 mg per kilogram of body weight weekly to day 90 , then monthly to day 360 after transplantation ) were compared with controls not given immunoglobulin . By chance , the immunoglobulin group included more patients with advanced-stage neoplasms ; otherwise , the study groups were balanced for prognostic factors . RESULTS Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative , but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody ( median titer , 1:64 ) . Among the 61 seronegative patients who could be evaluated , none contracted interstitial pneumonia ; among the 308 seropositive patients evaluated , 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication ( P = 0.021 ) . Control patients had an increased risk of gram-negative septicemia ( relative risk = 2.65 , P = 0.0039 ) and local infection ( relative risk = 1.36 , P = 0.029 ) and received 51 more units of platelets than did immunoglobulin recipients . Neither survival nor the risk of relapse was altered by immunoglobulin . However , among patients greater than or equal to 20 years old , there was a reduction in the incidence of acute GVHD ( 51 percent in controls vs. 34 percent in immunoglobulin recipients ; P = 0.0051 ) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow ( 46 percent vs. 30 percent ; P = 0.023 ) . CONCLUSIONS Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD , associated interstitial pneumonia , and infections after bone marrow transplantation The safety and pharmacokinetics of the two neutralizing human IgG1 monoclonal antibodies to cytomegalovirus ( CMV ) SDZ 89 - 104 and 89 - 109 in bone marrow transplant ( BMT ) recipients was assessed in an open phase I trial . Thirteen patients , 8 seropositive and 5 seronegative for CMV , were treated with allogeneic or autologous bone marrow transplantation . SDZ 89 - 104 was given to 5 and SDZ 89 - 109 to 8 patients . Patients were divided into high- and low-dose groups . A fixed pre study dose of 0.1 mg/kg was given 4 days before BMT . On days 3 , 17 , 31 , 45 , 59 , and 73 , patients were treated with either 0.5 or 2 mg/kg of the respective antibody . Results indicate that doses of 2 mg/kg of SDZ 89 - 104 or SDZ 89 - 109 in alternating weeks can be safely administered to BMT patients . Serum trough levels measured by antiidiotype ELISA were approximately 10 micrograms/ml after administration of 0.5 mg/kg and approximately 50 micrograms/ml after treatment with 2 mg/kg of SDZ 89 - 104 or SDZ 89 - 109 . High serum levels defined by antiidiotype ELISA techniques closely paralleled increased neutralizing activity . Serum half-lives calculated from these data were approximately 6 days In an effort to prevent cytomegalovirus infection among seronegative patients having marrow transplants , a globulin with high antibody levels against cytomegalovirus was given before and for 11 weeks after transplantation in a r and omized trial . Among 36 patients who received no prophylactic granulocyte transfusions , globulin recipients had significantly fewer infections than controls ( 2 of 17 versus 8 of 19 , p = 0.05 by Fisher 's exact test and p = 0.03 by Mantel-Cox test ) . Conversely , infection rates were high and unchanged by globulin use among patients who received granulocytes from seropositive donors ( 7 of 8 recipients versus 6 of 7 controls ) . The lack of effect of the globulin among patients receiving transfusions of granulocytes from seropositive donors may suggest that the dose of antibody was insufficient or that antibody is ineffective against virus transmitted in granulocytes . We conclude that cytomegalovirus infection can be prevented by immunoprophylaxis in seronegative patients having marrow transplants who are not given granulocyte transfusions Cytomegalovirus ( CMV ) infection is a frequent cause of morbidity and mortality after allogeneic bone marrow transplantation [ 1 , 2 ] . Approximately 50 % of all allogeneic transplant recipients develop CMV infection , which is more common in CMV-seropositive patients [ 1 ] . Some patients with CMV infection are asymptomatic , but many develop pneumonia , gastroenteritis , fever and wasting , or hepatitis . In a recent review of CMV infection at several transplant centers , the average incidence of CMV pneumonia in allogeneic transplants was 15 % , and the mortality was 80 % to 90 % [ 1 ] . Treatment of CMV pneumonia with antiviral agents or intravenous immunoglobulin has generally been ineffective [ 1 ] , although the combination of ganciclovir and immunoglobulin has been reported to increase survival to 50 % to 60 % at some centers [ 3 - 5 ] . Attempts to prevent CMV infection and disease in bone marrow transplant recipients have produced mixed results . In CMV-seronegative patients , most CMV infections can be prevented by the use of CMV-seronegative blood products [ 6 ] . Prophylactic intravenous immunoglobulin also modifies the severity of CMV infection in CMV-seronegative patients and decreases the risk for acute graft-versus-host disease ( GVHD ) and interstitial pneumonia [ 7 , 8 ] . On the other h and , effective prophylaxis for CMV reactivation and pneumonia in patients who are CMV-seropositive at the time of transplantation has not been clearly established . Previous trials of prophylactic vidarabine , human leukocyte interferon , and low-dose acyclovir showed no clinical ly significant effect [ 1 ] . In a nonr and omized , controlled trial , high doses of prophylactic acyclovir were associated with a decreased incidence of CMV infection and CMV disease [ 9 ] . However , the incidence of CMV infection and CMV-related pneumonia was 59 % and 19 % , respectively , despite the high doses of acyclovir . The efficacy of CMV immune plasma or immunoglobulin in CMV-seropositive patients is also uncertain [ 7 , 10 , 11 ] . Ganciclovir , an acyclic nucleoside analog of guanosine , has recently become available for treatment of CMV infection in immunocompromised patients [ 12 ] . In vitro , ganciclovir is approximately 50 times more active than acyclovir against CMV isolates [ 13 ] . Thus , we initiated a placebo-controlled , double-blind , r and omized trial of prophylactic ganciclovir in CMV-seropositive allogeneic bone marrow transplants . Methods From May 1987 to August 1990 , patients hospitalized at the UCLA Center for the Health Sciences were enrolled in the study if they met the following criteria : undergoing allogeneic bone marrow transplantation for hematologic malignancy or aplastic anemia ; 12 years of age or older ; seropositive for CMV antibody ; and no evidence of pneumonia or other CMV clinical syndrome . Informed consent approved by the UCLA Human Subject Protection Committee was obtained from each patient . Patients undergoing a second bone marrow transplant were excluded . Only three patients meeting the eligibility criteria and subsequently approached for consent refused to participate in the study . Transplant Procedure Details on conditioning therapy before transplantation and clinical management after transplantation have been reported previously [ 14 - 16 ] . Patients were given high-dose chemotherapy alone or with radiation therapy followed by intravenous infusion of bone marrow from a related or unrelated donor . Cyclosporine alone or in combination with methotrexate , corticosteroids , T-cell depletion , or immunotoxin ( Xomazyme-CD5 ; Xoma Corporation , Berkeley , California ) was used to prevent GVHD . Patients who developed GVHD were evaluated by st and ard criteria and treated with either corticosteroids alone or corticosteroids plus immunotoxin [ 14 - 16 ] . Trimethoprim-sulfamethoxazole was administered to all patients between the seventh and second days before transplantation and then for 2 consecutive days of each week between day 40 and day 150 after transplantation to prevent Pneumocystis carinii pneumonia [ 1 ] . Neither prophylactic acyclovir nor intravenous immunoglobulin was used . All patients received unscreened blood products that were not tested for CMV antibody . Study Drugs Patients were r and omly assigned in a double-blind fashion to receive ganciclovir or placebo through a central intravenous catheter . The ganciclovir was given at a dosage of 2.5 mg per kg body weight every 8 hours intravenously , starting on the day that pretransplant conditioning therapy was initiated ( usually day 7 before transplant ) and continuing until the day before the bone marrow infusion . After transplantation , when the neutrophil count reached 1.0 109/L , the ganciclovir was resumed at a dosage of 6 mg/kg once per day , Monday through Friday , and continued until day 120 after transplant . The dosage was adjusted in patients with renal failure . For patients whose neutrophil count fell below 1.0 109/L while receiving the study drug , prophylaxis was temporarily discontinued . When the neutrophil count returned to a level greater than 1.0 109/L , the ganciclovir was restarted at a dosage of 6 mg/kg once per day on Monday , Wednesday , and Friday . If a patient developed documented interstitial pneumonia , gastrointestinal disease , or other clinical syndromes related to CMV , the primary physician could remove the patient from the study and treat the patient with ganciclovir . Laboratory Procedures The cytomegalovirus serologic status of patients and bone marrow donors was determined by latex agglutination ( CMV SCAN ; Becton Dickinson , Cockeysville , Maryl and ) . After transplantation , serologic studies for CMV antibody were done every 2 to 4 weeks on all patients by both complement-fixation and enzyme-linked immunosorbent assay ( ELISA ) ( CMV ELISA-IgG ; Pharmacia Diagnostics , Fairfield , New Jersey ) . Viral cultures of throat , urine , and buffy coat were obtained from marrow transplant recipients before entry into the study and then once a week . Whenever appropriate , viral cultures of suspicious lesions , bronchoalveolar lavage , biopsy material , and autopsy tissue were performed . Tissue cultures were initially screened for viral antigen by immunofluorescence using monoclonal antibodies to viral proteins and then observed for 4 weeks to detect characteristic cytopathic effects . Bronchoalveolar lavage and biopsy material were also examined histologically for typical viral inclusion s and immunohistochemically by indirect immunofluorescence using murine monoclonal antibodies to early and late CMV proteins . Complete blood counts and tests for serum creatinine , electrolytes , and liver function were done before , during , and after the study period to assess patients for treatment-related side effects . Diagnosis of Cytomegalovirus Infection and Disease Cytomegalovirus infection was diagnosed by isolation of CMV from a culture obtained from any site , a fourfold or greater increase in the CMV antibody titer on complement fixation , an increase in the CMV ELISA measurement to 1.1 units or greater , or the presence of typical CMV inclusion bodies in a tissue specimen . Interstitial pneumonia was diagnosed by tachypnea , hypoxemia , fever , and interstitial pulmonary infiltrates on a chest roentgenogram not explainable by other obvious causes . Cultures , histologic examination , and immunochemical staining of bronchoalveolar lavage or lung biopsy were done to determine the cause of interstitial pneumonia . Similarly , cultures , histologic examination , and immunochemical staining of an endoscopic biopsy of the gastrointestinal tract or a biopsy of the liver in a patient with associated symptoms and signs were used to diagnose CMV disease of the gastrointestinal tract and liver . The wasting syndrome related to CMV was defined as fever , anorexia , and weight loss not explainable by other causes in a patient with culture or serologic evidence of CMV infection . Statistical Analysis The Fisher exact test was used to compare differences in proportions . The Student t-test was used to compare means . Univariate comparisons of times to specific events were performed by the method of Kaplan and Meier and analyzed by the log-rank test . Confidence intervals ( CIs ) for 95 % of differences are given where appropriate . Results Patient Characteristics One hundred thirty patients were enrolled in the study . However , 45 patients ( 20 placebo patients , 25 ganciclovir patients ) were considered nonevaluable and were excluded from the efficacy analysis . Reasons for nonevaluability were as follows : early death within 9 to 34 days after the transplant ( 24 patients ) , marrow graft failure preventing administration of the study drug after transplant ( 9 patients ) , withdrawal of patient from the study ( 10 patients ) , and inadvertent enrollment of a patient undergoing a second transplant ( 2 patients ) . Fifteen placebo patients and 18 ganciclovir patients were not evaluable due to either early death or graft failure . Eight of the 45 patients removed from the study subsequently developed CMV infection ( asymptomatic CMV excretion in five patients , fever and wasting in one patient , and pneumonia in two patients ) . The one patient with a CMV wasting syndrome and one of the two patients with pneumonia were initially r and omized to receive ganciclovir . The other patient with CMV pneumonia was r and omized to receive placebo . None of these patients received study drug after the transplant , and none was taking study drug when CMV disease developed . All determinations of evaluability were done blindly without knowledge of the patient 's treatment assignment and before the study code was broken . The characteristics of the 85 evaluable patients are summarized in Table 1 . Forty-five patients received placebo , and 40 patients were given ganciclovir . The two groups of patients were similar in terms of age , sex , underlying disease , marrow source , GVHD prophylaxis , and the marrow donor 's CMV serologic status . More patients in the ganciclovir group received HLA-mismatched marrow ( 95 % CI , 29 % to 2 % ; P = 0.04 ) The effects of passive immunization on cytomegalovirus infection and interstitial pneumonia in marrow transplants were evaluated in a r and omized , controlled trial . Twenty-four patients received cytomegalovirus immune plasma before and after transplantation , and 24 patients were controls . Although the incidence of cytomegalovirus infection was similar in the control and plasma groups , symptomatic infection ( 12 of 24 versus five of 24 , p = 0.07 ) and interstitial pneumonia ( 11 of 24 versus five of 24 , p = 0.12 ) occurred less frequently in the group receiving plasma . Cytomegalovirus infection occurred in 11 of 13 recipients of leukocyte transfusions and in 16 of 35 patients not given leukocyte transfusions ( p = 0.02 ) . Among patients not given leukocyte transfusions , the incidence of cytomegalovirus infection was similar in the control and plasma groups , but symptomatic infection ( eight of 18 versus one of 17 , p = 0.03 ) and interstitial pneumonia ( nine of 18 versus one of 17 , p = 0.01 ) were significantly less in the group receiving plasma . These results suggest that passive immunization modifies cytomegalovirus infection in humans and prevents interstitial pneumonia in marrow transplants especially when leukocyte transfusions are not used Patients with plateau-phase multiple myeloma have an increased risk of life-threatening bacterial infections and polyclonal humoral immune suppression . We conducted a r and omised , double-blind , placebo-controlled , multicentre trial of intravenous immunoglobulin ( IVIg ) as prophylaxis against infection . 82 patients with stable multiple myeloma received monthly infusions of IVIg at 0.4 g/kg body weight or an equivalent volume of placebo ( 0.4 % albumin ) intravenously for 1 year . Other interventions , including chemotherapy , were not affected ; no patient received prophylactic antibiotics . There were no differences at entry or on study in clinical or laboratory variables between patients in the two groups . There were no episodes of septicaemia or pneumonia in patients receiving IVIg compared with 10 in placebo patients ( p = 0.002 ) . There were 57 serious infections ; 38 occurred in 470 patient-months on placebo , compared with 19 in 449 patient-months on IVIg ( p = 0.019 ) . IVIg also protected against recurrent infections ( p = 0.021 ) in 60 patients who completed a year . Before treatment , 54 patients were immunised with Pneumovax and specific IgG responses were measured . A poor pneumococcal IgG antibody response ( less than 2-fold increase ) identified patients who had maximum benefit from IVIg . Mild adverse reactions were noted in 12 % of IVIg infusions and 5 % of placebo infusions . IVIg can be given safely to plateau-phase myeloma patients . It protects against life-threatening infections and significantly reduces the risk of recurrent infections . The individuals who benefit most can be identified prospect ively by measuring IgG antibody responses to pneumococcal immunisation A r and omized multicentre study was conducted to evaluate the effect of anti-CMV hyperimmune globulin in the prophylaxis of CMV infections in CMV seronegative allogeneic BMT patients who received a transplant from a seropositive donor or who had received blood products unscreened for CMV during the treatment before BMT . Twenty-eight patients were included in the study . Thirteen were r and omized to receive and 15 not to receive intravenous CMV hyperimmune globulin . A dose of 0.4 g/kg of immunoglobulin was given on day −8 and 0.2 g/kg on days −1 , + 7 , + 14 , + 21 , + 28 , + 35 , + 42 , + 56 and + 70 in relation to the day of transplantation . Among the 15 patients not given immunoglobulin CMV was isolated in three , and two of them developed clinical CMV disease . In addition , one more patient developed CMV antibodies without virus isolation . In five of the 13 patients given immunoglobulin the virus could be isolated , and four of them developed CMV disease . One additional patient showed seroconversion but no other findings of CMV infection . The incidence of acute and chronic GVHD was similar in the two arms . There was no significant difference in survival . In conclusion , the present results do not indicate a beneficial effect of CMV hyperimmune globulin infusions in the prophylaxis of CMV infection or disease in seronegative allogeneic bone marrow transplant recipients from a seropositive donor We have completed a r and omized trial to evaluate the safety and effectiveness of hyperimmune cytomegalovirus intravenous human globulin in prevention of cytomegalovirus infection and related problems in bone marrow transplant recipients . Prophylactic intravenous administration of this native , intact , hyperimmune , cytomegalovirus IgG , at a dose of 200 mg/kg 25 , 50 , and 75 days following transplant result ed in complete protection against cytomegalovirus infection during the 120 days covered by the treatment ( p = 0.009 ) . There was no interstitial pneumonia or mortality in the group receiving the hyperimmune IgG. This is significant at the p = 0.014 when compared with the supporting treatment control group . In bone marrow transplant recipients , prophylaxis with a total dosage of 0.6 g/kg of an intravenous hyperimmune cytomegalovirus globulin was safe and afforded effective protection against cytomegalovirus infection and interstitial pneumonia in this high-risk population MSL-109 is a monoclonal antibody specific to the cytomegalovirus ( CMV ) glycoprotein H with high neutralizing capacity . In a prospect i ve , r and omized , double-blind study , allogeneic hematopoietic stem cell transplantation ( HSCT ) recipients with positive donor and /or recipient serology for CMV before transplantation received either 60 mg/kg MSL-109 ( n = 59 ) , 15 mg/kg MSL-109 ( n = 60 ) , or placebo ( n = 60 ) intravenously every 2 weeks from day -1 until day 84 after transplantation . CMV pp65 antigenemia , CMV-DNA load in plasma , and viremia by culture were tested weekly . Primary end points were development of pp65 antigenemia at any level and /or viremia for which ganciclovir was given . There was no statistically significant difference in CMV pp65 antigenemia or viremia among patients in the 60-mg group ( pp65 antigenemia , 47 % ; viremia , 15 % ) , the 15-mg group ( 52 % ; 23 % ) , and the placebo group ( 45 % ; 17 % ) . There was also no difference in maximum levels of pp65 antigenemia , time to clearance of pp65 antigenemia after start of ganciclovir , CMV disease , invasive bacterial and fungal infections , time to neutrophil and platelet engraftment , acute graft-versus-host disease , days of hospitalization , and overall survival rate among the 3 groups . However , a subgroup analysis of CMV-seronegative recipients with a seropositive donor ( D+/R- ) showed a transiently improved survival rate by day 100 in MSL-109 recipients ( mortality : 60-mg group , 1/13 ; 15-mg group , 1/12 ; placebo group , 6/10 [ P = .02 for 60-mg versus placebo groups ; P = .08 for 15-mg versus placebo groups ] ) ; by the end of follow-up , the difference was no longer statistically significant . The improved survival rate in D+/R- patients could not be attributed to a reduction in CMV disease ; however , MSL-109 was associated with improved platelet engraftment and less grade III to IV acute graft-versus-host disease in this subgroup . In a subgroup analysis of CMV-seropositive recipients of MSL-109 ( D+/R+ and D-/R+ ) , overall mortality was increased compared to that of the placebo group ( P = .12 for the 60-mg versus placebo groups , P = .05 for the 15-mg versus placebo groups , and P = .04 for the dose levels combined versus placebo ) . MSL-109 was well tolerated and no immune response to the drug was observed . Thus , MSL-109 was safe but did not reduce CMV infection in allogeneic HSCT recipients . The transient survival advantage seen early after transplantation in CMV D+/R- patients and the negative effect on survival in seropositive patients remain unexplained . Thus , there is no evidence that MSL-109 is beneficial in CMV-seropositive HSCT recipients Intravenous immunoglobulin has been used after bone marrow transplants to prevent infections and acute graft-versus-host disease . However , the minimum dose required for protection is unknown . This may have significant economic implication s. A multicenter r and omized clinical trial compared the impact of two intravenous immunoglobulin doses on systemic infections and acute graft-versus-host disease in transplant recipients . Either 250 mg/kg or 500 mg/kg was given weekly from day −8 to day + 111 . Multivariate analysis was used to assess the effect of dose and other risk factors on event-free survival , systemic infection , and acute graft-versus-host disease . The two-dose cohorts had similar event-free survival and infection frequencies . The higher dose was associated with less acute graft-versus-host disease ( P = 0.03 ) Cytomegalovirus (CMV)-specific immunoglobulin ( IVIG ) was evaluated in a r and omized controlled trial in CMV-seronegative marrow transplant patients with seropositive marrow donors for the prevention of primary CMV infection during the first 100 days after transplant . Patients received 200 mg/kg CMV IVIG on days 8 and 6 before transplant , the day after transplant , weekly for the first month , and then every 2 weeks to complete 10 doses . Patients were followed with weekly CMV cultures and serologic studies and for clinical and histologic evidence of CMV disease . Sixty patients were evaluable in each group . There was significantly less CMV excretion ( P = .04 ) and viremia ( P = .01 ) in the treatment group . However , the incidence of CMV disease including CMV pneumonia , CMV enteritis , and CMV syndrome ( fever , leukopenia , hepatitis ) was not statistically different . There was also no difference in median time of onset of CMV infection or disease , median number of hospital days , or survival between the two groups Ninety-seven patients r and omized to receive ( 45 patients ) or not to receive ( 52 patients ) intravenous cytomegalovirus immune globulin before and after allogeneic marrow transplantation were evaluated retrospectively for the occurrence of bacterial and fungal septicemia in the first 100 days post-transplant . In a proportional hazards regression test , infection prevention regimens , immunoglobulin administration , age and occurrence of acute graft-versus-host disease were tested simultaneously for the occurrence of septicemia in the pre- and post-engraftment period . Of these factors , only patients receiving immunoglobulin had significantly fewer episodes of septicemia following engraftment with 11 ( 26 % ) patients in the globulin group having 14 episodes compared to 22 ( 42 % ) patients in the control group having 27 episodes ( p = 0.039 ) . None of the patients experienced complications with the immunoglobulin infusions . These results suggest that the administration of intravenous immunoglobulin may be a practical and effective method to decrease the incidence of septicemia following marrow transplantation Zymosan opsonisation was determined in sera of 38 normal individuals and 20 children with acute lymphocytic leukemia ( ALL ) . All patients underwent chemotherapy according to the CoALL 82 protocol . Intravenous gammaglobulin ( ivGG ) was given prophylactically to replace deficient specific antibodies . Zymosan opsonisation in normal sera ranged from 65 % to 133 % of a serum pool , whereas sera of children with ALL exhibited markedly decreased opsonisation ranging from 7 % to 141 % ( of the pooled serum st and ard ) at different times during an observation period of 20 months . No significant changes could be observed over time , neither induced by the ivGG infusion itself ( short term effect ) nor during the 20 months observation period ( long term effect ) . Before ivGG therapy was initiated , a positive correlation was found between zymosan opsonisation and complement parameters ( CH 50 : p less than 0.01 ; AP 50 ; p less than 0.001 ; C3 : p less than 0.05 ) . No correlation could be noted between zymosan opsonisation and IgG concentration . Experiments with complement deficient sera clearly demonstrated the dependence of zymosan opsonisation from complement function . In contrast , sera with little or no IgG but intact complement , showed normal zymosan opsonisation . Deficient zymosan opsonisation might contribute to the immune deficiency of ALL patients . The present study suggests , that the zymosan opsonisation can not be corrected by ivGG infusions The effects of i.v . cytomegalovirus ( CMV ) immunoglobulin given for prophylaxis of CMV infections in recipients of allogeneic and autologous marrow transplants were evaluated in a r and omized trial : 60 patients were r and omly assigned to receive ( 30 patients ) or not to receive ( 30 patients ) CMV immunoglobulin for a period of 90 days after transplantation . As to the allografted patients , the cumulative incidence of asymptomatic and symptomatic CMV infections was significantly reduced in the CMV immunoglobulin-treated group as compared to the control group ( 56.5 % versus 92.9 % , P less than 0.05 ) . No other statistically significant effect of CMV immunoglobulin could be found . In particular , the incidence of symptomatic CMV infections ( including interstitial pneumonia ) , the mean delay of post-transplant viraemia and haematopoietic recovery were similar in the control and CMV immunoglobulin-treated groups . We conclude that prophylactic CMV immunoglobulin administration , as design ed in our study , is no more than marginally effective and can not be recommended without additional trials Children receiving cytotoxic drugs were given 7 S IgG or placebo before the period of neutropenia ( less than 500/mm3 neutrophils ) in a double-blind study . Though the IgG levels differed significantly , fever as the most reliable sign of infection occurred not less often than in the placebo-group . There is no indication for the routinely prophylactic administration of immunoglobulins to oncological patients . The therapeutic benefit of immunoglobulin substitution in cancer patients needs verification Recent reports using historical controls or registry cohorts suggest , respectively , either an increase in the mortality or a decrease in the incidence of hepatic veno-occlusive disease ( VOD ) with the administration of intravenous immunoglobulin ( i.v . Ig ) after bone marrow transplantation . These divergent results prompted us to conduct a retrospective analysis of two r and omized clinical trials conducted at our center to determine the effect of i.v . Ig infusions on the development and severity of VOD . Patients were r and omized to receive ( n=318 ) or not to receive ( n=315 ) i.v . Ig prophylaxis after human leukocyte antigen-identical sibling ( n=414 ) , mismatched or unrelated ( n=178 ) , or autologous or syngeneic ( n=41 ) marrow transplantation . To determine the relationship of i.v . Ig to the development and severity of VOD , a single observer review ed data displays created for each patient for grading VOD without knowledge of patient i.v . Ig use . In this analysis , VOD was defined as hyperbilirubinemia > or = 2.0 mg/dL before day 20 and abrupt weight gain > or = 2 % before day 14 posttransplant in the absence of other causes of liver disease . Hepatic VOD developed in 235 ( 37 % ) of the 633 r and omized patients . No evidence for VOD was found in 230 ( 36 % ) patients . The remaining 168 ( 27 % ) patients were classified as having liver disease of uncertain etiology . Hepatic VOD was judged to be severe in 63 ( 10 % ) and mild or moderate in 172 ( 27 % ) patients . The number of patients developing any VOD or severe VOD was similar between those r and omized to i.v . Ig prophylaxis and untreated controls ( 115 vs. 120 and 32 vs. 31 , respectively ) . Logistic regression models identified several covariates as significant ( p < 0.01 ) factors associated with the development of severe VOD . Increased risk occurred with elevated pretransplant serum aspartate aminotransferase ( odds ratio [ OR ] = 2.64 ) and earlier year of transplant ( OR = 3.73 ) ; decreased risk occurred with autologous or twin donors ( OR = 0.09 ) and acute myeloid leukemia ( OR = 0.39 ) . The development of any VOD was associated with an elevated pretransplant alkaline phosphatase ( OR = 4.1 ) , pretransplant use of vancomycin ( OR = 1.6 ) or amphotericin ( OR = 3.0 ) , posttransplant use of cyclosporine ( OR = 2.5 ) , older patient age ( OR = 1.03 ) , and obesity ( OR = 0.78 ) . We concluded from the controlled trials of 633 patients that the administration of i.v . Ig did not influence the development or severity of VOD after bone marrow transplantation Graft-vs.-host disease ( GVHD ) and infection are major complications of allogeneic bone marrow transplantation . Intravenous immunoglobulin ( IVIg ) given at a dose of 500 mg/kg/wk has been shown to decrease the risk of acute GVHD , interstitial pneumonia , and infection in adults early after allogeneic transplantation . The current study is a controlled trial to determine whether a lower total dose of IVIg given with pretransplant loading reduces the incidence of transplant-related complications . In a r and omized trial of 241 patients > or = 20 years of age who were given related donor marrow allografts , 121 individuals receiving Ig prophylaxis ( 500 mg/kg/d loading from day -6 to -1 and then 100 mg/kg every 3 days from day 3 to 90 ) were compared with 120 control patients who did not receive IVIg . R and omization was stratified by human leucocyte antigen-matching , remission status of malignancy , GVHD prophylaxis , and cytomegalovirus ( CMV ) serology . The study was powered to detect a reduction in acute GVHD by 18 % and a decrease in transplant-related mortality by 17 % . Pretransplant IVIg loading and posttransplant maintenance achieved median serum IgG levels > 1350 mg/dL , which were approximately twofold greater than the untreated controls ( p<0.01 ) . White blood cell and platelet recoveries were similar for the two groups , although control patients required fewer units of platelets per day ( 2.5 vs. 3.3 , p = 0.008 ) . No significant differences in the incidence of CMV infection , interstitial pneumonia , or bacteremia were observed . The incidence of acute GVHD did not differ between the two groups ; however , acute GVHD was less frequent among IVIg recipients achieving maximum serum IgG levels > 3000 mg/dL ( 60 vs. 79 % ) . Neither transplant-related mortality nor disease-free survival was significantly altered by Ig prophylaxis . However , the cumulative incidence of relapse of malignancy was higher in IVIg recipients than in controls ( 31 vs. 18 % , p = 0.03 ) . Multivariable regression analysis demonstrated a 1.89 increased relative risk of relapse for individuals given IVIg ( p = 0.021 ) . We conclude that pretransplant loading and a shorter course and lower total dose of IVIg prophylaxis did not appear to decrease the risk of acute GVHD or mortality among adults receiving related donor marrow transplants . Note , IVIg administration may be associated with an increased risk of recurrent malignancy , a finding that warrants further investigation Bone marrow transplantation recipients who were cytomegalovirus ( CMV ) seropositive and /or had a CMV seropositive donor were r and omized for treatment with CMV hyperimmune plasma ( n = 27 ) or no treatment at all ( n = 27 ) . The CMV hyperimmune plasma had neutralization titers greater than 250 and enzyme-linked immunosorbent assay titers greater than 18,000 . Plasma ( 200 mg/kg body weight ) was given on four occasions ( during 2 days ) from day 3 to day 76 after transplantation . Patient characteristics were similar in the two groups . After transplantation , the median CMV titers increased with greater than 100 % in the group receiving the CMV plasma and decreased to less than 50 % in the controls ( p less than 0.01 ) . Asymptomatic CMV infections occurred in 26 % of the patients in the plasma group and 33 % of the controls . The frequency of patients with symptomatic CMV infections was also the same in the two groups ( 51 % vs 33 % ) . Three patients each in the two groups developed CMV-associated interstitial pneumonitis . Patient survival and causes of death were similar in the two groups . To conclude , no beneficial effect of CMV hyperimmune plasma was seen in patients at high risk of developing CMV infections In an attempt to reduce the incidence of lethal cytomegalovirus ( CMV ) interstitial pneumonitis after allogenic bone marrow transplantation 49 patients were r and omized in a multicenter controlled study to receive either CMV-hyperimmune globulin or a control immune globulin with low anticytomegalovirus titer . Immune globulin was administered intravenously 6 times with 20 days interval , starting on day 7 before transplantation . Patients receiving CMV hyperimmune globulin or control immune globulin were comparable with regard to age , diagnosis , pretransplant anti-CMV titer , incidence of graft-versus-host disease and transfusions . In each group , the incidence of histologically proven CMV interstitial pneumonitis during the first 110 days post BMT was recorded . Six of 23 patients in the control group versus 1 of 26 in the CMV hyperimmune globulin group died of CMV interstitial pneumonitis ( p less than 0.05 ) . No significant effect on idiopathic pneumonitis or survival was observed Intravenous immunoglobulin replacement therapy reduces the number of bacterial infections in B-cell chronic lymphocytic leukaemia ( B-CLL ) patients . However , due to the complexity of immunodeficiency in B-CLL and the cost-effectiveness of replacement therapy , it is important to identify patients who are likely to benefit from the treatment and to investigate which dose should be used . 15 patients with hypogammaglobulinaemia and a history of recurrent infections received a fixed dose of 10 grams of gammaglobulin intravenously every 3 weeks . Serum IgG levels were significantly higher after three doses ( p = 0.0002 ) , and stabilized just above lower reference value after 11 doses . The total number of infection-related events during 168 months before therapy was compared to the total number of infection-related events in 169 months during therapy . The number of antibiotic prescriptions was reduced from 78 to 54 ( N.S. ) , the number of admissions to hospital due to infections was reduced from 16 to 5 ( p = 0.047 ) and the number of febrile episodes was reduced from 63 to 31 ( p = 0.004 ) . We conclude that a fixed low dose of gammaglobulin intravenously can restore normal serum IgG levels in hypogammaglobulinaemic B-CLL patients , and leads to a decreased number of febrile episodes and admissions to hospital due infections Thirty-two patients undergoing allogeneic hematopoietic stem-cell transplantation were given respiratory syncytial virus ( RSV ) immune globulin ( RSVIG ) at the time of transplantation and again 3 weeks later . Antibody titers to RSV , human parainfluenza virus 3 , measles , and influenza H1N1 , H3N2 , and B were measured prior to administration of RSVIG and 6 more times over the course of the subsequent 6 weeks . Baseline antiviral titers and increases in antibody after administration of RSVIG were extremely variable for all the viruses . In 18 patients in whom the baseline titers of antibody titers to RSV-F protein were 1:640 - 1:2048 , there was a 7.7-fold initial increase in these titers after the first dose of RSVIG , compared with a 2.1-fold increase in 14 patients with baseline titers of 1:4096 - 1:20,840 ; increases in titers of antibody against the other viruses after the first dose of RSVIG reflected similar variability . The subset of patients with the lowest titers appear to receive the greatest benefit from administration of RSVIG BACTERIAL infection is one of the leading causes of morbidity and mortality in patients with multiple myeloma.1 , 2 Although most patients have large amounts of homogeneous myeloma immunoglobulin p The efficacy of i.v . immunoglobulin plus CMV-seronegative blood products or CMV-seronegative blood products alone for prevention of CMV infection , symptomatic CMV disease , other infections and GVHD after BMT was evaluated in a r and omized , controlled trial . Fifty-one CMV-seronegative allogeneic BMTs with a CMV-seronegative or CMV-seropositive marrow donor were r and omly assigned to receive either i.v . immunoglobulin ( 1.0 g/kg once weekly for 120 days after transplant ) plus CMV-seronegative blood products or CMV-seronegative blood products alone . CMV infection occurred in 2 of 25 patients ( 7 % ) receiving i.v . immunoglobulin plus CMV-seronegative blood and in 2 of 23 patients ( 9 % ) receiving CMV-seronegative blood alone . All CMV infections were asymptomatic and characterized by viral excretion with or without CMV seroconversion . There were no cases of CMV-related interstitial pneumonia . Grade > or = II GVHD was less frequent in patients given i.v . immunoglobulin ( 5 of 25 patients ( 20 % ) vs. 11 of 23 patients ( 48 % ) , p = 0.04 ) . The number of bacterial and fungal infections was similar in both groups . Fewer non-CMV viral infections ( 9 of 27 patients ( 33 % ) vs. 15 of 24 patients ( 63 % ) , p = 0.03 ) and fewer deaths associated with infection ( 1 of 27 patients ( 4 % ) vs. 5 of 24 patients ( 21 % ) , p = 0.07 ) occurred in recipients of immunoglobulin . Neither survival nor risk of leukemia relapse was changed by the immunoglobulin . The high doses of i.v . immunoglobulin were well tolerated . These results suggest that CMV-seronegative blood products alone prevent most CMV infections and CMV disease in CMV-seronegative allogeneic BMT recipients , even when the marrow donor is CMV-seropositive . ( ABSTRACT TRUNCATED AT 250 WORDS We have used sample s from the in vivo situation to compare antibody levels provided by the infusion of different IVIG products , a measure , albeit indirect , of potential therapeutic efficacy . The further correlation of in vivo antibody titers with functional activities of these antibodies ( eg , opsonization and viral neutralization ) would provide additive valuable information about the usefulness of this therapy The pharmacokinetics of an intravenous immunoglobulin ( IVIG ) , Gammagard ( Baxter Healthcare Corp. , Glendale , CA ) , were measured in 31 cytomegalovirus ( CMV ) antibody negative bone marrow transplant ( BMT ) patients as part of a multicenter efficacy trial of 2 weekly dose regimens . Since all patients lacked antibody to CMV and received only screened CMV negative blood products , the half-life of the exogenous CMV antibody could be measured with an ELISA assay . The CMV antibody titer was related to the immunoglobulin concentration using a st and ard curve . Compared with the 22-day half-life in normal subjects , the half-life in BMT patients was approximately 6 days for either the 250 mg/kg or 500 mg/kg dose regimen . The half-life did not change over the subsequent 3 weekly doses . Peak concentrations were 3.5 + /- 1.4 and 2.6 + /- 0.7 mg/mL of IVIG in week 1 as well as 5.5 + /- 2.6 and 3.4 + /- 1.2 mg/mL in week 3 after the 250 mg/kg and 500 mg/kg , respectively . Total body clearance of IVIG was 0.61 and 0.46 mL/kg/hr for the 500 mg/kg and 250 mg/kg , respectively |
2,188 | 24,429,420 | Switching improved serum lipids significantly .
Of the studied triple-NRTI combinations only abacavir/lamivudine/zidovudine was sufficiently potent .
Triple-NRTI maintenance after successful induction with two-class cART appeared successful in treatment-naive subjects and remains a useful option in specific circumstances , especially when other drugs are not available or drug interactions are an issue | BACKGROUND Single-drug class regimens with nucleoside/nucleotide reverse transcriptase inhibitors ( NRTIs ) are generally not recommended as initial therapy because they are inferior compared with therapy with two NRTIs plus efavirenz .
However , triple-NRTI combinations can be useful in specific circumstances such as in tuberculosis coinfection , pregnancy or dyslipidaemia .
Here , we review the potential of such combinations to maintain viral suppression after induction of suppression by st and ard combination antiretroviral therapy ( cART ) and to evaluate the trade-off of NRTI-only regimens for metabolic control . | OBJECTIVE To examine the antiviral potency and tolerability profile of a single-class four drug ( quadruple ) nucleoside reverse transcriptase inhibitor ( NRTI ) regimen compared with a 2-class st and ard-of-care regimen . METHODOLOGY A three-centre , r and omized , open-label comparative pilot study of zidovudine/lamivudine/efavirenz ( triple ) versus abacavir/lamivudine/zidovudine/tenofovir ( quadruple ) therapy in HIV-1-infected , treatment-naive individuals . Both regimens were taken without regard to food and consisted of a twice-daily regimen and 3 pills/day . The study power was based on time-weighted average changes in HIV-1 RNA load . RESULTS A total of 114 individuals ( 56 triple , 57 quadruple ) received at least one dose of medication . Patients were well matched at baseline for viral load ( mean 5.26 log10 versus 5.13 log10 , respectively ) and CD4 cell count ( median 193 versus 153 cells/mm3 , respectively ) . The two regimens performed similarly with regards to all endpoints . At week 48 , by intention-to-treat , missing = failure analysis , 68 % of triple- and 67 % of quadruple-drug treated patients had an HIV-1 RNA < 50copies/ml ( P>0.05 ) . On-treatment analysis showed 40/40 ( 100 % ) of triple- and 39/40 ( 97.5 % ) of quadruple-drug treated patients ( P=0.996 ) had responded to < 50copies/ml . No unexpected adverse events were reported . Changes in total cholesterol and triglycerides were modest but significantly favoured the quadruple therapy regimen at multiple time points . CONCLUSION This pilot study suggests a quadruple NRTI-based regimen provides similar antiviral potency , tolerability and administrative characteristics to a 2-class triple therapy regimen . These findings should be confirmed in a more fully powered study . Potent quadruple NRTI-based regimens may have advantages for some individuals with regards to salvageability , tolerability and drug interactions CONTEXT Abacavir , a nucleoside analogue , has demonstrated suppression of human immunodeficiency virus ( HIV ) replication alone and in combination therapy . However , the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a st and ard protease inhibitor-containing regimen for initial antiretroviral treatment . OBJECTIVE To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen . DESIGN AND SETTING A multicenter , phase 3 , r and omized , double-blind trial with an enrollment period from August 1997 to June 1998 , with follow-up through 48 weeks at 73 clinical research units in the United States , Canada , Australia , and Europe . PATIENTS Five hundred sixty-two antiretroviral-naive , HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. INTERVENTIONS Patients were stratified by baseline HIV RNA level and r and omly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo . After 16 weeks , patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving r and omized treatment or receive open-label therapy . MAIN OUTCOME MEASURE Virologic suppression , defined as HIV RNA concentration of 400 copies/mL or less at week 48 . RESULTS The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group ( 51 % [ 133/262 ] ) and in the indinavir group ( 51 % [ 136/265 ] ) with a treatment difference of -0.6 % ( 95 % confidence interval [ CI ] , -9 % to 8 % ) . In patients with baseline HIV RNA levels greater than 100 000 copies/mL , the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45 % ( 45/100 ) vs 31 % ( 30/96 ) and a treatment diference of -14 % ( 95 % CI , -27 % to 0 % ) . The 2 treatments were comparable with respect to their effects on CD4 cell count . There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities . One death in the abacavir group was attributed to hypersensitivity reaction , which occurred following rechallenge with abacavir , approximately 3 weeks after initiating study treatment . CONCLUSIONS In this study of antiretroviral-naive HIV-infected adults , the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks BACKGROUND The most effective highly active antiretroviral therapy ( HAART ) to prevent mother-to-child transmission of human immunodeficiency virus type 1 ( HIV-1 ) in pregnancy and its efficacy during breast-feeding are unknown . METHODS We r and omly assigned 560 HIV-1-infected pregnant women ( CD4 + count , > or = 200 cells per cubic millimeter ) to receive coformulated abacavir , zidovudine , and lamivudine ( the nucleoside reverse-transcriptase inhibitor [ NRTI ] group ) or lopinavir-ritonavir plus zidovudine-lamivudine ( the protease-inhibitor group ) from 26 to 34 weeks ' gestation through planned weaning by 6 months post partum . A total of 170 women with CD4 + counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine ( the observational group ) . Infants received single-dose nevirapine and 4 weeks of zidovudine . RESULTS The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery ( 96 % in the NRTI group , 93 % in the protease-inhibitor group , and 94 % in the observational group ) or throughout the breast-feeding period ( 92 % in the NRTI group , 93 % in the protease-inhibitor group , and 95 % in the observational group ) . By 6 months of age , 8 of 709 live-born infants ( 1.1 % ) were infected ( 95 % confidence interval [ CI ] , 0.5 to 2.2 ) : 6 were infected in utero ( 4 in the NRTI group , 1 in the protease-inhibitor group , and 1 in the observational group ) , and 2 were infected during the breast-feeding period ( in the NRTI group ) . Treatment-limiting adverse events occurred in 2 % of women in the NRTI group , 2 % of women in the protease-inhibitor group , and 11 % of women in the observational group . CONCLUSIONS All regimens of HAART from pregnancy through 6 months post partum result ed in high rates of virologic suppression , with an overall rate of mother-to-child transmission of 1.1 % . ( Clinical Trials.gov number , NCT00270296 . BACKGROUND We investigated virological response and the emergence of resistance in the Nevirapine or Abacavir ( NORA ) sub study of the Development of Antiretroviral Treatment in Africa ( DART ) trial . METHODS Six hundred symptomatic antiretroviral-naive human immunodeficiency virus (HIV)-infected adults ( CD4 cell count , < 200 cells/mm(3 ) ) from 2 Ug and an centers were r and omized to receive zidovudine-lamivudine plus abacavir or nevirapine . Virology was performed retrospectively on stored plasma sample s at selected time points . In patients with HIV RNA levels > 1000 copies/mL , the residual activity of therapy was calculated as the reduction in HIV RNA level , compared with baseline . RESULTS Overall , HIV RNA levels were lower in the nevirapine group than in the abacavir group at 24 and 48 weeks ( P < .001 ) , although no differences were observed at weeks 4 and 12 . Virological responses were similar in the 2 treatment groups for baseline HIV RNA level < 100,000 copies/mL. The mean residual activity at week 48 was higher for abacavir in the presence of the typically observed resistance pattern of thymidine analogue mutations ( TAMs ) and M184V ( 1.47 log(10 ) copies/mL ) than for nevirapine with M184V and nonnucleoside reverse-transcriptase inhibitor mutations , whether accompanied by TAMs ( 0.96 log(10 ) copies/mL ) or not ( 1.18 log(10 ) copies/mL ) . CONCLUSIONS There was more extensive genotypic resistance in both treatment groups than is generally seen in re source -rich setting s. However , significant residual activity was observed among patients with virological failure , particularly those receiving zidovudine-lamivudine plus abacavir Objective To compare the safety/tolerability of abacavir and nevirapine in HIV-infected adults starting antiretroviral ( ARV ) therapy in Ug and a. Methods Twenty-four-week r and omized double-blind trial conducted with 600 symptomatic ARV-naive adults with CD4 < 200 cells/mm3 allocated to zidovudine/lamivudine plus 300 mg abacavir ( A ) and nevirapine placebo ( n = 300 ) or 200 mg nevirapine ( N ) and abacavir placebo ( n = 300 ) twice daily . The primary endpoint was any serious adverse event ( SAE ) definitely/probably or uncertain whether related to blinded nevirapine/abacavir . Secondary endpoints were adverse events leading to permanent discontinuation of blinded nevirapine/abacavir , and grade 4 events . Results Seventy-two per cent participants were women ; 19 % had WHO stage 4 disease ; the median age was 37 years ( range 18–66 ) ; the median baseline CD4 count was 99 cells/mm3 ( 1–199 ) . Ninety-five per cent completed 24 weeks : 4 % died and 1 % were lost to follow-up . Thirty-seven SAEs occurred on blinded drug in 36 participants . Twenty events [ 6 ( 2.0 % ) abacavir , 14 ( 4.7 % ) nevirapine participants ] were considered serious adverse reactions definitely/probably/uncertain whether related to blinded abacavir/nevirapine [ HR = 0.42 ( 95 % CI 0.16–1.09 ) P = 0.06 ] . Only 2.0 % of abacavir participants [ six patients ( 0.7–4.3 % ) ] experienced a suspected hypersensitivity reaction ( HSR ) . In total 14 ( 4.7 % ) abacavir and 30 ( 10.0 % ) nevirapine participants discontinued blinded abacavir/nevirapine ( P = 0.02 ) : because of toxicity ( 6A , 15N ; P = 0.07 , all rash/possible HSR and /or hepatotoxicity ) , anti-tuberculosis therapy ( 6A , 13N ) , or for other reasons ( 2A , 2N ) . Conclusions There was a trend towards a lower rate of serious adverse reactions in Ug and an adults with low CD4 starting ARV regimens with abacavir than with nevirapine . This suggests that abacavir could be used more widely in re source -limited setting s without major safety concerns Background Hyperlipidemia secondary to protease inhibitors ( PI ) may abate by switching to anti-HIV medications without lipid effects . Method An open-label , r and omized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia ( fasting serum total cholesterol > 200 mg/dL ) who were r and omized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily ( n = 52 ) or a regimen in which their PI was continued ( n = 52 ) for 28 weeks . All patients had undetectable viral loads ( HIV-1 RNA < 50 copies/mL ) at baseline and were naïve to abacavir and non-nucleoside reverse transcriptase inhibitors . Results At baseline , the mean total cholesterol was 243 mg/dL , low density lipoprotein (LDL)-cholesterol 149 mg/dL , high density lipoprotein (HDL)-cholesterol 41 mg/dL , and triglycerides 310 mg/dL. Mean CD4 + cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms , respectively . At week 28 , the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol ( -42 vs -10 mg/dL , P < 0.001 ) , LDL-cholesterol ( -14 vs + 5 mg/dL , P = 0.016 ) , and triglycerides ( -134 vs -36 mg/dL , P = 0.019 ) than the PI-continuation arm , with no differences in HDL-cholesterol ( + 0.2 vs + 1.3 mg/dL , P = 0.583 ) . A higher proportion of patients in the abacavir-switch arm had decreases in protocol -defined total cholesterol and triglyceride toxicity grade s , whereas a smaller proportion had increases in these toxicity grade s. At week 28 , an intent-to treat : missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA < 400 or < 50 copies/mL or adjusted mean change from baseline in CD4 + cell count . Two possible abacavir-related hypersensitivity reactions were reported . No significant changes in glucose , insulin , insulin resistance , C-peptide , or waist-to-hip ratios were observed in either treatment arm , nor were differences in these parameters noted between treatments . Conclusion In hyperlipidemic , antiretroviral-experienced patients with HIV-1 RNA levels < 50 copies/mL and CD4 + cell counts > 500 cells/mm3 , substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period , and it simplifies treatment BACKGROUND Observational and retrospective clinical trial cohorts have reported conflicting results for the association of abacavir use with risk of myocardial infa rct ion ( MI ) , possibly related to issues that may bias estimation of treatment effects , such as time-varying confounders , informative dropout , and cohort loss due to competing events . METHODS We analyzed data from 5056 individuals initiating r and omized antiretroviral treatment ( ART ) in AIDS Clinical Trials Group studies ; 1704 started abacavir therapy . An intent-to-treat analysis adjusted for pretreatment covariates and weighting for informative censoring was used to estimate the hazard ratio ( HR ) of MIs after initiation of a regimen with or without abacavir . RESULTS Through 6 years after ART initiation , 36 MI events were observed in 17,404 person-years of follow-up . No evidence of an increased hazard of MI in subjects using abacavir versus no abacavir was seen ( over a 1-year period : P=.50 ; HR , 0.7 [ 95 % confidence interval { CI } , 0.2 - 2.4 ] ) ; over a 6-year period : P=.24 ; HR , 0.6 [ 95 % CI , 0.3 - 1.4 ] ) ; these results were robust over as-treated and sensitivity analyses . Although the risk of MI decreased over time , there was no evidence to suggest a time-dependent abacavir effect . Classic cardiovascular disease ( CVD ) risk factors were the strongest predictors of MI . CONCLUSION We find no evidence to suggest that initial ART containing abacavir increases MI risk over short-term and long-term periods in this population with relatively low MI risk . Traditional CVD risk factors should be the main focus in assessing CVD risk in individuals with human immunodeficiency virus infection Background Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection , but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine . We aim ed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy . Methodology /Principal Findings Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a r and omized single blinded clinical trial . R and omisation was between zidovudine-containing therapy ( zidovudine/lamivudine+lopinavir/ritonavir ) and zidovudine-sparing therapy ( nevirapine+lopinavir/ritonavir ) . Main outcome measures were body composition assessed by computed tomography and dual-energy X-ray absorptiometry scan and lipid profile before and after 3 , 12 , 24 months of antiretroviral therapy . In the zidovudine/lamivudine+lopinavir/ritonavir group , from 3 months onward limb fat decreased progressively by 684±293 grams ( estimated mean±st and ard error of the mean)(p = 0.02 ) up to 24 months whereas abdominal fat increased , but exclusively in the visceral compartment ( + 21.9±8.1 cm2 , p = 0.008 ) ) . In contrast , in the nevirapine+lopinavir/ritonavir group , a generalized increase in fat mass was observed . After 24 months no significant differences in high density lipoprotein and total/high density lipoprotein cholesterol ratio were found between both treatment groups , but total and low density lipoprotein cholesterol levels were higher in the nevirapine+lopinavir/ritonavir group ( 6.1±0.2 versus 5.3±0.2 and 3.6±0.1 versus 2.8±0.1 mmol/l respectively , p<0.05 ) . Virologic response and safety were comparable in both groups . Conclusions / Significance Zidovudine/lamivudine+lopinavir/ritonavir , but not nevirapine+lopinavir/ritonavir in antiretroviral therapy-naïve patients , is associated with lipoatrophy and greater relative intraabdominal lipohypertrophy , suggesting that zidovudine/lamivudine contributes to both these features of lipodystrophy . These findings support to no longer consider zidovudine/lamivudine as one of the preferred possible components of first-line antiretroviral therapy where alternative treatments are available . Trial Registration Clinical Trials.gov NCT We evaluated a single-class quadruple nucleoside/nucleotide regimen in a 96-week prospect i ve one-arm pilot study in adult HIV-infected naive patients with CD4 > 100 cells/microl . St and ard zidovudine/lamivudine/abacavir and tenofovir doses were given . Virologic efficacy was evaluated by intent-to-treat ( ITT ) , switch = failure and on-treatment ( OT ) analyses . A total of 54 patients were included ( median CD4 count 254 cells/microl , VL 79,706 copies/ml ) . A median drop in VL of 2 log at 14 days and > 3 log since week 12 was observed . A total of 34/54 ( 63 % ) patients ( ITT ) and 34/39 ( 87 % ) patients ( OT ) had VL < 50 copies/ml at 96 weeks . Four ( 7 % ) patients switched therapy due to adverse events , 5 ( 9 % ) had virologic failure , and 1 died . Similar efficacy results were observed irrespective of baseline VL ( > or < 5 log ) or CD4 cells ( > or < 250/microl ) . A median CD4 gain of + 223 cells/microl was achieved . K65R + 41L + 219Q were detected in one patient at virologic failure . Only two patients presented fat loss on clinical evaluation . A decrease in total cholesterol ( p = 0.007 ) and LDLc ( p = 0.016 ) was observed . Our data suggest that zidovudine/lamivudine/abacavir plus tenofovir is a simple , effective , and well-tolerated NNRTI/PI-sparing regimen , even for patients with high viral loads . Larger trials comparing this option with st and ard initial antiretroviral regimens should be conducted Background Traditional first line regimens containing a non-nucleoside reverse transcriptase inhibitor or protease inhibitor may not be suitable for a subset of antiretroviral-naïve patients such as those with certain co-morbidities , women of child-bearing potential , and intolerability to components of st and ard first line therapy . This study was conducted to determine if alternate treatment options may meet the needs of both general and special patient population s. The ACTION study was a r and omized , open-label , multicenter , 48-week trial that compared the safety and efficacy of a triple nucleoside regimen versus a protease inhibitor plus a dual nucleoside regimen in HIV-1 treatment-naïve subjects . Results 279 HIV-infected subjects with HIV-1 RNA ( VL ) > 5000 but < 200,000 copies/mL ( c/mL ) and CD4 + count ≥ 100 cells/mm3 were r and omized ( 1:1 ) to receive abacavir sulfate/lamivudine/zidovudine ( ABC/3TC/ZDV ) twice-daily or atazanavir ( ATV ) once-daily plus lamivudine/zidovudine ( 3TC/ZDV ) twice-daily . Protocol -defined virologic failure was based on multiple failure criteria .Non-inferiority of ABC/3TC/ZDV to ATV+3TC/ZDV was established with 62 % vs. 59 % of subjects achieving a VL < 50 c/mL at week 48 , [ ITT(E ) , M/S = F , 95 % CI : -5.9 , 10.4 ] . Similar results were observed in the 230 ( 82 % ) subjects with baseline VL<100,000 c/mL ( ABC/3TC/ZDV vs. ATV+3TC/ZDV ) , 66 % vs. 59 % ; 95 % CI : -5.6 , 19.5 . However , ABC/3TC/ZDV did not meet the non-inferiority criterion compared to ATV+3TC/ZDV in the 48 subjects with baseline VL ≥ 100,000 c/mL , 39 % vs. 60 % ; 95 % CI : -49.2 , 7.4 , respectively . Protocol -defined virologic failure was similar between groups . Conclusion ABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks . In those with a baseline VL ≥ 100,000 c/mL , subjects in the ATV+3TC/ZDV showed better virologic efficacy . Both regimens offer benefits in select therapy-naïve subjects . Trial Registration [ Clinical Trials Identifier , NCT00082394 ] This r and omized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens ( n=79 ) or a change to the simplified regimen of abacavir-lamivudine-zidovudine ( n=84 ) in patients with suppressed human immunodeficiency virus type 1 ( HIV-1 ) RNA for > or = 6 months who did not have the reverse transcriptase 215 mutation . After a median follow-up of 84 weeks , virologic failure was 6 % in the continuation and 15 % in the simplified group ( P=.081 ) . Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure . Study treatment was discontinued because of adverse events in 20 % of the continuation and 7 % of the simplified group ( P=.021 ) . Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels ; however , this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen BACKGROUND We assessed the strategy of substituting nevirapine , efavirenz , or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 ( HIV-1 ) in whom virologic suppression had been achieved . METHODS We r and omly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine ( 155 patients ) , efavirenz ( 156 ) , or abacavir ( 149 ) . The primary end point was death , progression to the acquired immunodeficiency syndrome , or an increase in HIV-1 RNA levels to 200 copies or more per milliliter . RESULTS At 12 months , the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group , 6 percent in the efavirenz group , and 13 percent in the abacavir group ( P=0.10 according to an intention-to-treat analysis ) . HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication ( 72 percent ) , and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients . Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors . Fewer patients in the abacavir group ( 6 percent ) than in the nevirapine group ( 17 percent ) or the efavirenz group ( 17 percent ) discontinued the study medication because of adverse events ( P=0.01 ) . The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group , but the prevalence of clinical lipodystrophy did not change significantly in the three groups . CONCLUSIONS When therapy was switched from a protease inhibitor to nevirapine , efavirenz , or abacavir in patients with virologic suppression , there was a trend toward a higher rate of virologic failure among those given abacavir Background : The mechanisms by which dyslipidemia and lipoatrophy develop during antiretroviral therapy are not clear . No treatment of lipoatrophy is currently established . Methods : This was an open‐label r and omized study of HIV‐positive individuals on a first‐line therapy containing stavudine ( d4 T ) with either a protease inhibitor ( PI ) or nonnucleoside reverse transcriptase inhibitor ( NNRTI ) and with hypercholesterolemia ( defined as total cholesterol > 5.2 mmol/L or > 180 mg/dL ) and /or lipoatrophy and with a viral load of < 50 copies/mL. Patients switched d4 T to abacavir ( ABC ) ( group 1 ) , a PI or NNRTI to ABC ( group 2 ) , or d4 T and PI or NNRTI to ABC plus AZT ( group 3 ) . Patients were followed‐up with fasting blood levels , dual‐energy X‐ray absorptiometry ( DXA ) , and computed tomography ( CT ) scans for 48 weeks . Results : Thirty patients were included , with 27 completing 48 weeks of therapy . One ABC hypersensitivity reaction was the only serious adverse event . All patients ' viral loads remained at < 50 copies/mL. CD4 cell counts rose in groups 2 and 3 but fell modestly in group 1 . Total and low‐density lipoprotein cholesterol improved significantly in groups 2 and 3 . Triglycerides fell significantly in group 2 . In contrast , total , arm , and leg fat mass ( by DXA ) rose significantly in group 1 but fell modestly in groups 2 and 3 . Visceral adiposity ( by CT scan ) was unaffected in all groups . Conclusions : Abacavir represents a virologically effective replacement for d4 T , PI , or NNRTI in persons on successful first‐line therapy . Replacement of a PI or NNRTI with ABC leads to modest improvement in both cholesterol and triglycerides . Replacement of d4 T with ABC leads to modest improvements in fat mass BACKGROUND Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 ( HIV-1 ) infection , but data from direct comparisons are limited . METHODS This r and omized , double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1 : zidovudine-lamivudine-abacavir , zidovudine-lamivudine plus efavirenz , and zidovudine-lamivudine-abacavir plus efavirenz . RESULTS We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 ( 71,434 ) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled . A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups . After a median follow-up of 32 weeks , 82 of 382 subjects in the triple-nucleoside group ( 21 percent ) and 85 of 765 of those in the combined efavirenz groups ( 11 percent ) had virologic failure ; the time to virologic failure was significantly shorter in the triple-nucleoside group ( P<0.001 ) . This difference was observed regardless of the pretreatment HIV-1 RNA stratum ( at least 100,000 copies per milliliter or below this level ; P < or = 0.001 for both comparisons ) . Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups . CONCLUSIONS In this trial of the initial treatment of HIV-1 infection , the triple-nucleoside combination of abacavir , zidovudine , and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides Objective : HIV‐1 protease inhibitors ( versus no protease inhibitors ) and stavudine ( versus zidovudine ) are independently associated with a higher risk of lipoatrophy in HIV‐infected patients . We sought to determine whether the revision of stavudine and /or protease inhibitor‐containing regimens to combivir/abacavir would result in prevention and /or reversibility of lipoatrophy in HIV‐1‐infected patients . Design : The investigation was a prospect i ve , r and omized , controlled , open‐label study . Subjects : The subjects included 37 HIV‐1‐infected individuals with stable undetectable HIV‐1 loads who were taking a regimen containing either stavudine or zidovudine with lamivudine and a protease inhibitor . Intervention : Subjects were r and omized to continue therapy or switch stavudine to zidovudine and protease inhibitor to abacavir , such that the universal switch regimen was combivir ( zidovudine/lamivudine ) and abacavir . Main Outcome Measures : Total body , leg , and arm fat mass was measured at baseline , 24 weeks , and 48 weeks using whole‐body dual‐energy x‐ray absorptiometry . Single‐cut L4 computed tomography and assays of multiple metabolic parameters were also performed . Results : There was an average gain in fat mass of 0.009 kg/(leg·mo ) in switch patients versus a loss of 0.010 kg/(leg·mo ) in controls ( p = .04 , on‐treatment analysis ) over 48 weeks . Significant arm fat restoration was observed in patients who switched regimens , with an average gain of 0.014 kg/(arm·mo ) ( p = .004 ) , whereas controls did not have a significant change from baseline . Analyses of percentage changes in arm and leg fat masses showed similar findings . No significant effects on intra‐abdominal fat , blood lipid levels , glycemic indices , and lactate levels were detected , although most baseline mean values were normal in study subjects . Combivir/abacavir maintained virological control in all but one case , and three ( 13.6 % ) of 22 individuals had adverse reactions to abacavir therapy . Conclusions : A switch to combivir/abacavir therapy was associated with objective evidence of limb fat‐sparing and fat restoration compared with continued treatment with stavudine and /or protease inhibitor OBJECTIVE To compare the efficacy and safety of a triple nucleoside combination to a protease inhibitor-containing triple regimen as first-line antiretroviral therapy ( ART ) in HIV-1-infected patients . DESIGN Open-label study in HIV-1-infected ART-naive adults , r and omized to receive either Combivir ( lamivudine 150 mg/zidovudine 300 mg twice daily ) + abacavir ( 300 mg twice daily ) , or Combivir + nelfinavir ( 750 mg every 8 h ) for 48 weeks . Plasma HIV-1 RNA , CD4 cell count and adverse events were assessed at baseline and weeks 4 , 8 , 16 , 24 , 32 , 40 and 48 . RESULTS 195 subjects ( 131 men , 64 women ) , median age 34 years , were r and omized : 98 received combivir/abacavir and 97 combivir/nelfinavir . Baseline median plasma HIV-1 RNA was 4.2 log10 copies/ml [ Interquartile range ( IQR ) : 3.7 - 4.5.2 ] and 4.1 log10 copies/ml ( IQR : 3.8 - 4.6 ) , respectively . Baseline median CD4 cell count was 387 cells/mm3 ( IQR : 194 - 501 ) and 449 cells/mm3 ( IQR : 334 - 605 ) , respectively . Nine patients ( 3 vs 6 , respectively ) did not start treatment or did not have any available efficacy data . At week 48 , using the intent to treat analysis ( switch/missing equals failure ) , plasma HIV-1 RNA was < 50 copies/ml in 54/95 ( 57 % ) and 53/91 ( 58 % ) of subjects , respectively . Median CD4 increase was + 110 and + 120 cells/mm3 , respectively . Possible hypersensitivity reactions to abacavir were reported in four subjects ( 4 % ) . CONCLUSION The triple nucleoside combination combivir/abacavir is well tolerated as a first-line ART regimen in HIV-1-infected adults , with comparable antiviral activity to a nelfinavir-containing regimen at week 48 Background : Highly active antiretroviral therapy containing three nucleoside reverse transcriptase inhibitors has been somewhat successful , but the clinical efficacy is unclear . Methods : R and omized , controlled , open-label trial of 180 antiretroviral drug-naive HIV-infected patients allocated to a regimen of abacavir , stavudine and didanosine ( A/S/D , n = 60 ) , ritonavir and saquinavir ( R/S 400/400 mg twice daily ; n = 60 ) or nelfinavir and nevirapine ( N/N 1250/200 mg twice daily ; n = 60 ) ; the latter two in combination with lamivudine and zidovudine . The primary endpoint was HIV plasma RNA ⩽ 20 copies/ml after 48 weeks . Results : At baseline , the median CD4 cell count was 161 × 106 cells/l ( range , 0–920 ) and the HIV RNA was 5.0 log10 copies/ml ( range , 2.7–6.7 ) . At 48 weeks , 43 % in the A/S/D arm had a HIV RNA ⩽ 20 copies/ml , compared with 69 % in the N/N arm ( P < 0.01 ) and 62 % in the R/S arm ( P < 0.05 ) . In a multivariate analysis , the A/S/D arm had an odds ratio of obtaining a viral load of ⩽ 20 copies/ml at week 48 of 0.25 [ 95 % confidence interval ( CI ) 0.10–0.59 ] versus N/N and 0.53 ( 95 % CI , 0.33–0.83 ) versus R/S. The A/S/D arm had a particularly poor outcome in patients with higher viral load and AIDS at baseline : 63 % had to discontinue A/S/D ( any drug ) . Side effects were more frequent in the A/S/D arm and included neuropathy 27 % , suspicion of hypersensitivity 12 % , and increase in lactate accompanied by systemic symptoms 8 % . Conclusion : The A/S/D regimen had a low efficacy and a high frequency of adverse events and can not be recommended BACKGROUND Risk factors for loss of virological response in patients receiving lopinavir/ritonavir ( LPV/r ) monotherapy as maintenance treatment have not been determined . METHODS In 121 patients enrolled in the OK and OK04 clinical trials assigned to receive monotherapy with LPV/r , we attempted to identify factors associated with loss of virological suppression at 48 weeks , defined as confirmed serum HIV type-1 RNA>50 copies/ml , with missing data or changes caused by toxicity censored . Univariate and multivariate Cox proportional hazard models were used to calculate hazard ratios for the risk of loss of virological suppression . RESULTS At week 48 , 15 patients experienced loss of virological suppression . Probability of loss of virological suppression was 12.7 % . Less than 9 months of maintenance of virological suppression prior to monotherapy , a lower baseline haemoglobin and low adherence measured by self-reported total missed doses in the week prior to study visit were associated with loss of virological suppression in the univariate analyses . Independent factors associated with loss of virological suppression by multivariate analyses were > or = 2 visits with self-reported missed doses in the week prior to the study visit , a lower baseline haemoglobin and a nadir CD4(+ ) T-cell count < 100 cells/microl . CONCLUSIONS Suboptimal adherence , lower baseline haemoglobin and a nadir CD4(+ ) T-cell count < 100 cells/microl were the main risk factors for losing virological suppression in patients r and omized to monotherapy with LPV/r In a prospect i ve , open-label , 104-week study , patients who were infected with human immunodeficiency virus type 1 ( virus load , < 50 copies/mL ) and who were receiving protease inhibitor-based therapy were r and omly assigned to continue treatment with a protease inhibitor or to replace it with abacavir or efavirenz . Treatment failure , defined as virological failure ( virus load , > 500 copies/microL ) or any clinical or biochemical adverse event with a grade of > or=3 ( on the basis of the World Health Organization [ WHO ] or American Heart Association [ AHA ] scales ) , was the primary outcome measurement . Failure rates were more frequent in the group treated with protease inhibitors ( P<.01 ) , and there were no significant differences in the rate of treatment failure between the group treated with efavirenz and the group treated with abacavir . Tolerability was better in the groups treated with abacavir or with efavirenz versus those treated with protease inhibitors . Fewer patients who received efavirenz experienced viral rebound . Among all groups , the mean increase in the CD4 cell count was 131 cells/microL ( P<.001 ) , with no significant difference between groups . This switching strategy maintains optimal levels of virological suppression and may improve lipid profiles in most patients Background : Treatment simplification in antiretroviral-experienced patients receiving protease inhibitor (PI)-containing antiretroviral regimens seems safe , but r and omized trials have limited power to detect differences in virological rebound ( VR ) between different switch strategies . Methods : From the French Hospital Data base on HIV , we selected 2462 patients with undetectable viral load ( VL ) who switched from a first PI-containing antiretroviral combination ( cART ) to a combination containing efavirenz ( EFV ) , nevirapine ( NVP ) or abacavir ( ABC ) . Factors associated with VR and with immunological efficacy ( gain of ≥ 50 CD4 + cells/μl ) were identified by using Cox models . Results : The 12-month Kaplan – Meier probabilities of VR were 6.8 , 13.7 and 12.3 % in patients switching to EFV-cART , NVP-cART and ABC-cART , respectively . Factors associated with VR were female sex , younger age , antiretroviral exposure before the first cART , time on first cART , higher VL at first cART initiation , a stavudine/didanosine backbone ( rather than zidovudine/lamivudine ) after the switch , and a switch to NVP or ABC [ respective adjusted hazard ratio versus EFV : 1.53 ; 95 % confidence interval ( CI ) , 1.21–1.94 ; and 1.53 ; 95 % CI , 1.12–2.08 ] . When the analyses were restricted to patients who were antiretroviral-naive before their first cART , NVP ( but not ABC ) was associated with VR . Immunological outcomes did not differ among the three switch regimens . Conclusion : When VL is undetectable on a first PI-cART regimen , switching to an EFV-containing regimen is more likely to avoid VR than switching to an ABC or NVP-containing regimen . ABC may be an alternative to EFV for patients who were not exposed to antiretroviral before their first cART regimen , after checking for ABC resistance mutations BACKGROUND Antiretroviral therapy is complicated by drug interactions and contraindications . Novel regimens are needed . METHODS This open label study r and omly assigned treatment-naive , human immunodeficiency virus (HIV)-infected subjects to receive tenofovir-emtricitabine with efavirenz ( Arm I ) , with ritonavir-boosted atazanavir ( Arm II ) , or with zidovudine/abacavir ( Arm III ) . Pair-wise comparisons of differences in time-weighted mean change from baseline plasma HIV-RNA to week 48 formed the primary analysis . Treatment arms were noninferior if the upper limit of the 95 % confidence interval ( CI ) was < 0.5 log(10 ) copies/mL. Secondary objectives included virologic , immunologic and safety end points . RESULTS The intention-to-treat population comprised 322 patients ( Arm I , n = 114 ; Arm II , n = 105 ; and Arm III , n = 103 ) . Noninferiority for the primary end point was established . Analysis for superiority showed that Arm III was significantly less potent than Arm I ( -0.20 log(10 ) copies/mL ; 95 % CI , -0.39 to -0.01 log(10 ) copies/mL ; P = .038 ) . The proportions of patients on each of Arm I ( 95 % ) and Arm II ( 96 % ) with < 200 copies/mL were not different ( P = .75 ) , but the percentage of patients in Arm III with < 200 copies/mL ( 82 % ) was significantly lower ( P = .005 ) . CD4 + cell counts did not differ . Serious adverse events were more frequent in Arm III ( n = 30 ) than in Arm I or Arm II ( n = 15 for each ; P = .062 ) . CONCLUSIONS A novel quadruple nucleo(t)side combination demonstrated significantly less suppression of HIV replication , compared with the suppression demonstrated by st and ard antiretroviral therapy regimens , although it did meet the predetermined formal definition of noninferiority . Secondary analyses indicated statistically inferior virologic and safety performance . Efavirenz and ritonavir-boosted atazanavir arms were equivalent in viral suppression and safety Patients who have not received previous antiretroviral treatment ( ART ) have a high failure rate on the combination treatment of abacavir , lamivudine , and tenovir . We assessed the virological failure rate in eight patients with HIV-1 who switched to this combination after having complete virological suppression from their previous long-term ART ( median 8.0 months , range 7.5 - 18.0 ) . Five of the eight patients showed virological failure . Four of these five patients had either the K65R mutation , the M184V/I mutation , or both . This combination of drugs can not therefore be recommended as alternative treatment in patients with HIV-1 who are fully virologically suppressed Background : Induction-maintenance strategies were associated with a low response rate . We compared the virological response with two different induction regimens with trizivir plus efavirenz or lopinavir/ritonavir . Methods : A r and omized , multicentre , open-label clinical trial with 209 antiretroviral-naive HIV-infected patients assigned to trizivir plus either efavirenz or lopinavir/ritonavir during 24–36 weeks . Patients reaching undetectable plasma viral loads during induction entered a 48-week maintenance on trizivir alone . The primary endpoint was the proportion of patients without treatment failure at 72 weeks using an intent to treat ( ITT ) analysis ( switching equals failure ) . Results : Patients were r and omly assigned ( efavirenz 104 ; lopinavir/ritonavir 105 ) , and 114 ( 55 % ) entered the maintenance phase ( efavirenz 54 ; lopinavir/ritonavir 60 ) . Baseline characteristics were balanced between groups . The response rate at 72 weeks was 31 and 43 % ( ITT analysis , P = 0.076 ) and 63 and 75 % ( on-treatment analysis , P = 0.172 ) in the efavirenz and lopinavir/ritonavir arms , respectively . Virological failure occurred in 27 patients : six during induction ( efavirenz , three ; lopinavir/ritonavir , three ; P = 1.0 ) and 21 during maintenance ( efavirenz , 14 ; lopinavir/ritonavir , seven ; P = 0.057 ) . Thirty-four patients in the efavirenz arm switched treatment because of adverse events compared with 25 in the lopinavir/ritonavir arm ( P = 0.17 ) . Conclusion : Trizivir plus either efavirenz or lopinavir/ritonavir followed by maintenance with trizivir achieved a low but similar response at 72 weeks , with a high incidence of adverse events leading to drug discontinuation during the induction phase in both arms . The study showed a trend towards an increased virological failure rate in the efavirenz arm during the maintenance phase Objective To assess the antiviral efficacy , safety and adherence in patients switched to an abacavir-containing nucleoside reverse transcriptase inhibitor ( NRTI ) regimen after long-term HIV-1 RNA suppression with a dual NRTI/protease inhibitor ( PI ) combination . Methods In an open-label , multicentre study , patients receiving 2NRTI plus PI for at least 6 months , with a history of undetectable plasma HIV-1 RNA since the initiation of therapy and plasma HIV-1 RNA < 50 copies/ml at screening , were r and omly assigned to replace the PI with abacavir ( n = 105 ) or continue the same treatment ( n = 106 ) . Clinical assessment s included plasma HIV-1 RNA , chemistry , haematology , lymphocyte counts , and adverse event reports . Adherence to treatment was assessed by patient self-report . Results A significantly longer time to treatment failure was demonstrated in the abacavir arm compared with the PI arm ( P = 0.03 ) while treatment failure was experienced by significantly more patients in the PI arm : 24 ( 23 % ) versus 12 ( 12 % ) ( P = 0.03 ) . Therapy-limiting toxicity led to treatment failure in eight versus 14 cases in the abacavir and PI arms , respectively , whereas virological rebound was the cause in four versus two cases . Significant reductions in cholesterol and non-fasting triglyceride plasma levels at 48 weeks were observed in the abacavir arm ( P < 0.001 and P = 0.035 , respectively ) . The number of patients reporting no difficulty in taking their therapy showed a marked increase from baseline in the abacavir arm . Conclusion The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression , significant improvements in lipid abnormalities and enhanced ease of dosing Objective : To compare one protease inhibitor (PI)-based and two PI-sparing antiretroviral therapy regimens . Methods : International , open label , r and omized study of antiretroviral drug-naive patients , with CD4 lymphocyte counts ⩾ 200 × 106 cells/l and plasma HIV-1 RNA levels > 500 copies/ml . Treatment assignment to stavudine and didanosine plus indinavir or nevirapine or lamivudine . Primary study endpoint was the percentage of patients with plasma HIV-1 RNA levels < 500 copies/ml after 48 weeks in the intention-to-treat analysis ( ITT ) . Results : In total , 298 patients were enrolled . After 48 weeks , the percentage of patients in the indinavir , nevirapine and lamivudine arms with HIV-1 RNA < 500 copies/ml was 57.0 % , 58.4 % and 58.7 % , respectively , in an ITT analysis . After 96 weeks of follow-up , these percentages were 50.0 % , 59.6 % and 45.0 % , respectively . The percentage of patients with HIV-1 RNA < 50 copies/ml was significantly less for those allocated to lamivudine in an on-treatment analysis after 48 and 96 weeks of follow-up . Patients in the nevirapine arm experienced a smaller increase in the absolute number of CD4 T lymphocytes . There were no significant differences in the incidence of serious adverse events . Conclusions : A comparable virological response can be achieved with first-line PI-base and PI-sparing regimens . The triple nucleoside regimen utilized may be less likely to result in viral suppression to < 50 copies/ml , while the nevirapine-based regimen is associated with a lower increase in CD4 T lymphocytes BACKGROUND The long-term effectiveness of potent three-drug antiretroviral regimens for the treatment of human immunodeficiency virus type 1 ( HIV-1 ) infection is limited by problems related to compliance and tolerability . We investigated whether two-drug maintenance therapy would suppress viral replication after a three-month period of aggressive triple-drug induction therapy . METHODS A total of 378 HIV-1-infected adults who had not received previous antiretroviral treatment received three months of induction therapy consisting of 300 mg of zidovudine every 12 hours , 150 mg of lamivudine every 12 hours , and 800 mg of indinavir every 8 hours . The 279 patients in whom the plasma HIV-1 RNA titer fell below 500 copies per milliliter after two months of triple-drug therapy , and who completed the induction phase , were r and omly assigned at month 3 to one of the following three open-label maintenance regimens : zidovudine , lamivudine , and indinavir ; zidovudine and lamivudine ; or zidovudine and indinavir . The primary end point was an increase in HIV-1 RNA levels to 500 copies or more per milliliter during the maintenance phase . RESULTS The proportion of patients who reached the primary end point was significantly higher among patients receiving zidovudine plus lamivudine ( 29 of 93 patients , P<0.001 ) or zidovudine plus indinavir ( 21 of 94 , P=0.01 ) than among patients receiving continued triple-drug therapy ( 8 of 92 ) . This higher failure rate in the groups treated with the two-drug maintenance regimens was also observed in the subgroup of patients with maximally suppressed HIV-1 RNA ( below 50 copies per milliliter ) at the time of r and omization to maintenance therapy . CONCLUSIONS In HIV-1-infected adults not previously treated with antiretroviral drugs whose plasma HIV-1 RNA levels fell below 500 copies per milliliter after three months of induction therapy with zidovudine , lamivudine , and indinavir , two-drug maintenance therapy was less effective in sustaining a reduced viral load than continued three-drug therapy Objective : To assess the virological , immunological and metabolic effects of switching from an efficacious first-line protease inhibitor (PI)-based HAART to a simplified triple nucleoside reverse transcriptase inhibitor ( NRTI ) regimen in children vertically infected with HIV . Design : Prospect i ve , open-label , before – after study of 20 vertically infected children with at least 12 consecutive months of undetectable viral load under a PI-based HAART and no previous history of NRTI treatment . Methods : At study entry , HAART was shifted to a triple-NRTI combination . Results : The children were aged 2 to 18 years ( median , 7.9 ) and were followed for 96 weeks . All were receiving a PI-based regimen for an average duration of 4 years before enrollment . At study entry , 12 patients ( 60 % ) switched to abacavir , 5 ( 25 % ) to lamivudine ; 2 ( 10 % ) to zidovudine and 2 to didanosine ( 10 % ) . All but one patient maintained plasma HIV RNA < 50 copies/ml during the entire follow-up . No immunological failure was observed at week 96 . A trend of normalization ( P < 0.001 ) of T cell receptor Vβ families of the CD8 cell subset was detected in 19/20 ( 95 % ) , with an increased HIV-specific CD8 T cell response ( P < 0.01 ) in 17/20 ( 85 % ) . Dyslipidaemia significantly improved during the follow up ( P < 0.001 ) . No new cases of lipodystrophy were detected . Conclusions : Switching to triple-NRTI regimens in selected HIV-infected children with an extremely low likelihood of harbouring nucleoside-associated mutations maintains viral suppression and immunological function , improving metabolic abnormalities and the effort to take medication for up to 96 weeks OBJECTIVE To study the antiviral efficacy and the mutations selected by a triple therapy with zidovudine ( AZT ) , lamivudine ( 3TC ) and tenofovir disoproxil fumarate ( TDF ) . METHODS Antiretroviral-naive patients received 300 mg AZT/150 mg 3TC twice a day plus 300 mg TDF once a day in an open pilot study . Follow-up was assessed at baseline therapy ( MO ) and at months 1 , 3 , 6 , 9 and 12 . Reverse transcriptase ( RT ) genotypic resistance analysis and in selected cases , a recombinant drug susceptibility and replication capacity assay were performed from plasma RNA at baseline and in case of virological failure ( VF ) ; that is , rebound of viral load > 50 copies/microl on therapy . RESULTS Twenty-four patients were included . At baseline , the median CD4 + T-cell count was 443 cells/microl and the median plasma viral load ( VL ) was 4.38 log10 copies/ml . RT resistance mutations were observed at MO in 4 patients . At M12 , the proportion of patients with a VL < 50 copies/ml reached 88 % using an on-treatment analysis and 67 % with an intent-to-treat analysis . The median increase in CD4 + T cells at M12 was 94 cells/microl . Four patients had a VF on therapy : two with wild-type viruses , one with selection of M184V and thymidine analogue mutations ( TAMs ) on a background of TAMs , and one with selection of K65R and M184V , with a replication capacity at 2.4%/o . CONCLUSION The virological response in our study demonstrates the antiviral efficacy of the AZT/3TC/TDF combination therapy , which needs further evaluation . The moderate frequency of selection of K65R could be due to the presence of AZT in the regimen Abstract Background : To assess the efficacy and safety of the triple NRTI combination of abacavir ( ABC ) , lamivudine ( 3TC ) , and tenofovir ( TDF ) in a once-daily regimen . Method : 38 HIV-naive patients ( pts ) were treated in a prospect i ve open-arm study over 48 weeks ( W48 ) . Virological failure was defined as never achieving plasma HIV-1 RNA < 400 copies/mL or rebound of ≥0.7 log10 . Results : 12/36 ( 33 % ) pts had virologic failure at W24 and 10 additional pts had HIV RNA > 50 copies/mL at W12 or W24 . There was a significant association between baseline viral load ( VL ) and virologic failure in 0 % , 29 % , and 64 % pts with baseline VL levels < 4 , 4 - 5 , and > 5 log10 copies/mL , respectively ( p = .014 ) . 76 % of pts developed K65R and M184V/I mutations by W24 , and 19 % developed M184V/I alone . At W4 , 86 % of pts had adequate plasma Cmin for the 3 drugs . 14 pts with K65R and M184V/I were given a rescue therapy with a successful outcome ( < 50 copies/mL ; median follow-up 48 weeks ) . Conclusion : Convergent genetic pathway to resistance , in conjunction with lower antiretroviral potency , may explain the high rate of selection K65R and M184V mutations . These mutations did not appear to have a negative effect on rescue therapy with a variety of regimens Abstract Purpose : To assess the safety and efficacy of a 4-drug , 3-tablet , once-daily ( qd ) regimen consisting of abacavir/lamivudine/zidovudine ( ABC/3TC/ZDV ; 2 tablets ) and tenofovir ( TDF ) in antiretroviral-naïve patients with plasma HIV-1 RNA ⩾30,000 copies/mL at 48 weeks . Method : All participants received ABC/3TC/ZDV ( 300/150/300 mg ) and TDF ( 300 mg ) qd in this pilot , open-label , multicenter study . Intent-to-treat ( ITT ) analyses were conducted to evaluate virologic and immunologic efficacy . Results : Of the 123 participants enrolled , 52 ( 42 % ) prematurely discontinued study for adverse events ( 14 ) , were lost to follow-up ( 13 ) , had virologic nonresponse ( 12 ) , and withdrew for other reasons ( 13 ) . At week 48 , by ITT missing = failure analysis , 41 % ( 51/123 ) and 51 % ( 63/123 ) of participants had plasma HIV-1 RNA < 50 copies/mL and < 400 copies/mL , respectively ; by ITT-observed analysis , 75 % ( 51/68 ) and 93 % ( 63/68 ) had plasma HIV-1 RNA < 50 copies/mL and < 400 copies/mL , respectively ; 11 % ( 14/123 ) met virologic nonresponse criteria . Median week 48 change in CD4 + cell count from baseline was + 127 cells/mm3 . Median week 48 changes from baseline for fasting lipids were as follows : cholesterol ( –9 mg/dL ) , HDL ( + 1 mg/dL ) , LDL ( –9 mg/dL ) , and triglycerides ( –4 mg/dL ) . Conclusion : A high rate of premature discontinuations contributed to the overall suboptimal virologic response to ABC/3TC/ZDV+TDF qd ; however , the regimen was not associated with high rates of virologic failure previously observed with TDF+ABC/3TC Prison inmates with human immunodeficiency virus ( HIV ) infection can be difficult to treat because of the complexity and intrusiveness of many combination antiretroviral therapy regimens . NZTA4007 , a 24-week open-label , single-arm clinical trial involving 108 antiretroviral therapy-naive , incarcerated , HIV-infected persons , was conducted to evaluate a compact regimen ( 4 tablets per day ) consisting of 1 lamivudine-zidovudine ( 150 mg/300 mg ) combination tablet ( COM ) and one 300-mg abacavir tablet administered twice daily under directly observed treatment conditions . In the intent-to-treat observed analysis , the plasma HIV type 1 ( HIV-1 ) RNA level remained at < or = 400 copies/mL in 85 % of the patients and at < 50 copies/mL in 75 % of the patients . Median change from baseline was -2.41 log(10 ) copies/mL for the HIV-1 RNA level and + 111 cells/mm(3 ) for the CD4 cell count . The overall adherence to prescribed doses was 94 % for patients who remained enrolled in the study . COM-abacavir given twice daily was generally well tolerated , and adverse events prompted only 4 patients to withdraw from the study BACKGROUND Combination antiretroviral therapy with indinavir , zidovudine , and lamivudine can suppress the level of human immunodeficiency virus ( HIV ) RNA in plasma below the threshold of detection for two years or more . We investigated whether a less intensive maintenance regimen could sustain viral suppression after an initial response to combination therapy . METHODS HIV-infected subjects who had CD4 cell counts greater than 200 per cubic millimeter , who had been treated with indinavir , lamivudine , and zidovudine , and who had less than 200 copies of HIV RNA per milliliter of plasma after 16 , 20 , and 24 weeks of induction therapy were r and omly assigned to receive either continued triple-drug therapy ( 106 subjects ) , indinavir alone ( 103 subjects ) , or a combination of zidovudine and lamivudine ( 107 subjects ) . The primary end point was loss of viral suppression , which was defined as a plasma level of at least 200 copies of HIV RNA per milliliter on two consecutive measurements during maintenance therapy . RESULTS During maintenance treatment , 23 percent of the subjects receiving indinavir and 23 percent of those receiving zidovudine and lamivudine , but only 4 percent of those receiving all three drugs , had loss of viral suppression ( P<0.001 for the comparison between triple-drug therapy and the other two maintenance regimens ) . Subjects with greater increases in CD4 cell counts during induction therapy , higher viral loads at base line ( i.e. , at the beginning of induction therapy ) , and slower rates of viral clearance were at greater risk for loss of viral suppression . The presence of zidovudine-resistance mutations in HIV RNA at base line was strongly predictive of the loss of viral suppression in subjects treated with zidovudine and lamivudine . CONCLUSIONS The suppression of plasma HIV RNA after six months of treatment with indinavir , zidovudine , and lamivudine is better sustained by the continuation of these three drugs than by maintenance therapy with either indinavir alone or zidovudine and lamivudine Background : High rates of virologic failure have been reported in antiretroviral-naive patients receiving triple-nucleoside reverse transcriptase inhibitor ( NRTI ) combinations containing tenofovir disoproxil fumarate ( TDF ) with lamivudine ( 3TC ) and didanosine or 3TC and abacavir ( ABC ) . A regimen of once-daily zidovudine ( ZDV ) , 3TC , ABC , and TDF showed an acceptable virologic success rate , however . Methods : This was a pilot prospect i ve cohort study . Treatment-naive subjects were offered a fixed-dose combination of ZDV/3TC ( 300 mg/150 mg ) twice daily and 300 mg of TDF once daily . Results : Fifty-one patients were enrolled between April 2002 and March 2005 . At baseline , the median CD4 count was 230 cells/μL ( range : 23 - 425 cells/μL ) , 20 ( 39 % ) of 51 subjects had CD4 counts of < 200 cells/μL , the median HIV-1 viral load was 4.89 log ( 3.14 to > 5.87 log ) , and 24 ( 47 % ) of 51 subjects had a viral load > 5 log . The median follow-up was 12 months ( range : 1 week to 38 months ) . On-treatment analysis showed a median HIV RNA load decrease of −1.7 log after 1 to 2 weeks of treatment and −2.41 log after 1 month , and 34 ( 89 % ) of 38 subjects had a viral load < 50 copies/mL at month 6 , 21 ( 78 % ) of 27 at month 12 , and 13 ( 81 % ) of 16 after 18 months ( intent-to-treat results were 34 [ 72 % ] of 47 subjects , 21 [ 56 % ] of 36 subjects , and 13 [ 50 % ] of 25 subjects at months 6 , 12 , and 18 , respectively ) . The median CD4 count increase at month 18 was 142 cells/μL. Nine ( 17.6 % ) of 51 treatment interruptions for adverse effects were seen . Six viral failures occurred , including 2 with K65R mutations ( alone or associated with Y115F and M184V ) . Conclusion : The combination of ZDV/3TC + TDF in treatment-naive HIV-infected subjects induces a rapid and sustained HIV-1 RNA decrease and is associated with a good immunologic response . No severe adverse events occurred . This triple-NRTI combination needs to be evaluated further Background : Patients with antiretroviral therapy (ART)-associated lipodystrophy frequently have disturbances in glucose metabolism associated with insulin resistance . It is not known whether changes in body composition are necessary for the development of these disturbances in ART-naive patients starting treatment with different combination ART regimens . Methods : Glucose metabolism and body composition were assessed before and after 3 months of ART in a prospect i ve r and omized clinical trial of HIV-1-positive ART-naive men taking lopinavir/ritonavir within either a nucleoside reverse transcriptase inhibitor (NRTI)-containing regimen ( zidovudine/lamivudine ; n = 11 ) or a NRTI-sparing regimen ( nevirapine ; n = 9 ) . Glucose disposal , glucose production and lipolysis were measured after an overnight fast and during a hyperinsulinaemic – euglycaemic clamp using stable isotopes . Body composition was assessed by computed tomography and dual-energy X-ray absorptiometry . Results : In the NRTI-containing group , body composition did not change significantly in 3 months ; insulin-mediated glucose disposal decreased significantly ( 25 % ; P < 0.001 ) ; and fasting glycerol turnover increased ( 22 % ; P < 0.005 ) . Hyperinsulinaemia suppressed glycerol turnover equally before and after treatment . The disturbances in glucose metabolism were not accompanied by changes in adiponectin or other glucoregulatory hormones . In contrast , glucose metabolism did not change in the NRTI-sparing arm . Glucose disposal significantly differed over time between the arms ( P < 0.01 ) . Conclusions : Treatment for 3 months with a NRTI-containing , but not a NRTI-sparing , regimen result ed in a 25 % decrease in insulin-mediated glucose disposal and a 22 % increase in fasting lipolysis . In the absence of discernable changes in body composition , NRTI may directly affect glucose metabolism , the mechanism by which remains to be eluci date BACKGROUND Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy . We compared 2 regimens dosed as 2 pills once daily . METHODS This was a r and omized , open-label , multicenter study of tenofovir disoproxil fumarate versus efavirenz , both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects . After reports of early nonresponse , an unplanned interim analysis was performed . Virologic nonresponse was defined as ( 1 ) a < 2.0-log(10 ) copies/mL decrease in HIV-1 RNA level by week 8 , ( 2 ) an HIV-1 RNA rebound of > or = 1.0 log(10 ) copies/mL above the nadir , or ( 3 ) for subjects with 2 consecutive HIV-1 RNA measurements < 50 copies/mL , a subsequent increase to > 400 copies/mL on 2 consecutive occasions . RESULTS We r and omized 340 subjects . Median baseline HIV-1 RNA level and CD4 + cell count were 4.7 log(10 ) copies/mL and 251 cells/mm3 , respectively ; 194 subjects with HIV-1 RNA data from > or = 8 weeks were included in the interim analysis . Virologic nonresponse occurred in 50 ( 49 % ) of 102 subjects in the tenofovir disoproxil fumarate arm , compared with 5 ( 5 % ) of 92 of subjects in the efavirenz arm ( P<.001 ) . Within 12 weeks , viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 ( 98 % ) of 41 subjects and K65R and M184V or mixtures in 22 ( 54 % ) of 41 subjects . The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm . The efavirenz arm continued unchanged ; after 48 weeks , 120 ( 71 % ) of 169 subjects achieved HIV-1 RNA levels < 50 copies/mL. CONCLUSION The tenofovir disoproxil fumarate/abacavir/lamivudine regimen result ed in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used Maintenance with a triple nucleoside reverse transcriptase Inhibitor ( NRTI ) regimen after successful induction with a dual NRTI/protease inhibitor ( PI ) combination may be advantageous , because of low pill burden , favorable lipids , and less drug interactions . This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested . We performed a r and omized , open-label , multicenter , 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 < or=350 cells/mm(3 ) and HIV-1 RNA concentrations ( viral load [ VL ] ) greater than 30,000 copies per milliliter . Patients were r and omized after reaching VL less than 50 copies per milliliter on two consecutive occasions between 12 and 24 weeks after start of zidovudine/lamuvidine and lopinavir/ritonavir combination . Eligible subjects switched to abacavir/lamivudine/zidovudine ( TZV ) or continued the PI-containing regimen . Here we present the 48-week data with virologic success rate ( failure : VL > 50 copies per milliliter ) . Two hundred seven patients had similar baseline ( BL ) characteristics : median CD4 180 cells/mm(3 ) , median VL 5.19 log(10 ) copies per milliliter . One hundred twenty subjects ( 58 % ) met r and omization criteria . Baseline VL differed significantly between dropouts and r and omized subjects ( median 5.41 versus 5.06 log(10 ) copies per milliliter , p = 0.017 ) , as did CD4 cells ( median 160 and 200 cells/mm(3 ) , p = 0.044 ) . Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI . At week 48 , 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression ( log rank test ; p = 0.379 ) . CD4 counts increased significantly in both arms . In ART-naïve patients , TZV maintenance had similar antiviral efficacy compared to continued st and ard ART at 48 weeks after baseline . Patients on successful st and ard ART can be safely switched to a NRTI-only regimen , at least for the tested time period Objectives : To assess the virologic noninferiority of an antiretroviral treatment simplification with coformulated zidovudine/lamivudine/abacavir ( group 1 ) vs. coformulated zidovudine/lamivudine plus nevirapine ( group 2 ) in HIV-1-infected patients receiving successful first-line highly active antiretroviral therapy . Methods : This is a prospect i ve , multicenter , open-label , comparative , r and omized , noninferiority study . A delta of 15 % for differences in virologic suppression < 200 copies/mL between groups was prespecified with a 1-sided 0.025 significance level . Results : A total of 134 patients were included into this study : 68 were allocated to group 1 and 66 to group 2 . By intention-to-treat analysis ( switch equals failure ) , the percentage of virologic suppression < 200 copies/mL ( < 50 copies/mL ) at week 48 was 71.0 % ( 65.1 % ) and 73.0 % ( 63.3 % ) in groups 1 and 2 , respectively ( estimate for differences [ < 200 copies/mL ] : −2.1 , 95 % CI : −17.4 - 13.1 , P = 0.783 ) . Thirteen and 14 patients in groups 1 and 2 , respectively , discontinued therapy due to adverse events . Dyslipidemia improved in both groups , with a higher improvement in low-density lipoprotein cholesterol ( P = 0.049 ) in group 1 . Conclusions : Group 1 is not inferior to group 2 regarding virologic suppression < 200 copies/mL. Both strategies improve lipid profile A r and omized controlled study exploring an induction-maintenance strategy was performed with a quadruple-drug regimen : zidovudine/lamivudine/abacavir/nevirapine . The study was prematurely interrupted due to the high proportion of adverse events . The median time on protocol -defined therapy was 110 days ; 13/28 ( 46 % ) patients interrupted therapy and 2/6 tested patients selected praecox viral mutants . Despite this , we observed a significant ( p < /= .001 ) increment of CD4 . The theoretical advantages of induction-maintenance strategies are tempered by an increased risk of adverse experiences OBJECTIVE To assess the antiviral efficacy , safety , and adherence in subjects who switched to Trizivir following long-term HIV-1 RNA suppression . STUDY DESIGN A r and omized , open-label , multicentre , 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months , with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening . METHODS Subjects were r and omized 1:1 to continue their current treatment or to switch to a simplified treatment with Trizivir administered twice daily . Assessment s included plasma HIV-1 RNA , lymphocyte counts , clinical laboratory evaluations , adverse events , and adherence to treatment ( obtained via subject self-report ) . Treatment failure was defined as a plasma viral load of > /= 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of r and omized treatment . RESULTS At week 48 , the proportion of treatment failures in Trizivir arm ( 23/106 , 22 % ) was noninferior to that observed in continued arm ( 23/103 , 22 % ) with a treatment difference stratified by prior ART of 1.2%[-10.1 ; 12.5 ] . Incidence of adverse events was similar in both treatment groups . The incidence of possible hypersensitivity reaction in the Trizivir trade mark arm was 10 % . Significant reductions in cholesterol and triglyceride plasma levels were observed in the Trizivir arm ( P < 0.001 and P = 0.006 , respectively ) . CONCLUSION Switching to Trizivir offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy SUMMARY Objective : An equivalence ( non-inferiority ) trial comparing antiviral response , tolerability , and adherence with a triple nucleoside regimen containing abacavir 300 mg ( ABC ) plus a lamivudine 150-mg/zidovudine 300-mg combination tablet ( COM ) twice daily vs. a regimen containing the protease inhibitor indinavir ( IDV ) 800 mg three times daily plus COM twice daily ( IDV/COM ) in antiretroviral-naïve , HIV-infected patients . Methods : Adult patients with plasma HIV-1 RNA levels ≥ 5000 copies/mL and CD4 + cell counts ≥ 100 cells/mm3 were r and omized to receive open-label ABC/COM ( n = 169 ) or IDV/COM ( n = 173 ) for 48 weeks . The intent-to-treat ( ITT ) population was the primary population evaluated . ITT : switch/missing equals failure ( ITT : S/M = F ) and as-treated ( AT ) analyses were used for assessing the proportion of patients achieving plasma HIV-1 RNA level < 400 and < 50 copies/mL at each clinic visit . In the ITT : S/M = F analysis , patients who switched treatment or had missing values were considered treatment failures ; the AT analysis examined virologic data only while patients received study treatment . ABC/COM was considered equivalent ( non-inferior ) to IDV/COM if the lower limit of the 95 % confidence intervals ( CIs ) about the difference in proportions of ABC/COM- vs. IDV/COM-treated patients attaining plasma HIV-1 RNA < 400 copies/mL exceeded –15 % at week 48 . Results : The study population was diverse with respect to ethnicity ( 38 % Asian , 27 % Hispanic , 28 % white , 3 % black , 4 % other ) and gender ( 39 % women , 61 % men ) . Baseline median HIV-1 RNA was 4.80 log10 copies/mL and CD4 + cell count was 315 cells/mm3 . ABC/COM met the criterion of equivalence to IDV/COM . In the ITT : S/M = F analysis at Week 48 , a greater proportion of ABC/COM-treated patients achieved HIV-1 RNA < 400 copies/mL ( 66 % [ 109/164 ] vs. 50 % [ 82/165 ] ; treatment difference 16.6 % , 95 % CI ( 6.0 , 27.2 ) , p = 0.002 ) and HIV-1 RNA < 50 copies/mL ( 60 % [ 99/164 ] vs. 50 % [ 83/165 ] ; treatment difference 9.6 % , 95 % CI [ –1.1 , 20.2 ] ) , whereas the AT analysis showed similar proportions achieving these endpoints ( < 400 copies/mL : 85 vs. 83 % ; < 50 copies/mL : 79 vs 81 % ) . Comparable proportions of patients with screening HIV-1 RNA values > 100 000 copies/mL achieved HIV-1 RNA < 400 copies/mL ( ABC/COM : 60 % [ 35/58 ] ; IDV/COM : 51 % [ 33/65 ] ; treatment difference 9.6 % , 95 % CI [ –7.9 , 27.1 ] ; ITT : S/M = F analysis ) . A significantly greater proportion taking ABC/COM were ≥ 95 % adherent ( 72 % [ 109/151 ] vs. 45 % [ 70/154 ] with IDV/COM , p < 0.001 ) . Median increases from baseline in CD4 + cell counts were similar in the two treatment groups ( + 148 vs. + 152 cells/mm3 ) . Significantly more patients on IDV/COM reported drug-related adverse events ( 87 % [ 142/165 ] vs. 65 % [ 108/164 ] with ABC/COM , p < 0.001 ) , similar proportions discontinued treatment due to adverse events ( 13 vs. 10 % ) , and a slightly greater proportion in the ABC/COM group reported serious adverse events ( 13 vs. 8 % ) . About half of the latter comprised suspected ABC-related hypersensitivity reactions ( overall rate , 6 % ) . Most adverse events were gastrointestinal in nature in both treatment groups . Conclusion : ABC/COM was at least equivalent to IDV/COM over 48 weeks in the treatment of antiretroviral-naïve patients . ABC/COM was associated with a significantly higher adherence rate and lower incidence of drug-related adverse events than IDV/COM . The study was limited in that it was not powered to determine equivalence of treatments within high vs. low viral load strata , adherence was not monitored electronically , and bias could not be ruled out due to the open-label study design Background : The ESS40013 study tested 4-drug induction followed by 3-drug maintenance as initial antiretroviral therapy ( ART ) to reduce HIV RNA rapidly and then to simplify to an effective yet more convenient and tolerable regimen . Methods : Four hundred forty-eight antiretroviral-naive adults were treated with abacavir/lamivudine/zidovudine ( ABC/3TC/ZDV ) and efavirenz ( EFV ) for the 48-week induction phase . Two hundred eighty-two patients were r and omized in a 1:1 ratio to continue ABC/3TC/ZDV + EFV or to simplify to ABC/3TC/ZDV for the 48-week maintenance phase . Results : The baseline median HIV RNA level and CD4 cell count were 5.08 log10 copies/mL ( 56 % ≥100,000 copies/mL ) and 210 cells/mm3 ( 48 % < 200 cells/mm3 ) , respectively . No significant differences were noted between ABC/3TC/ZDV + EFV and ABC/3TC/ZDV for an HIV RNA level < 50 copies/mL ( 79 % vs. 77 % [ intent to treat ( ITT ) , missing = failure ] ; P = 0.697 ) or time to treatment failure ( P = 0.75 ) at week 96 . Drug-related adverse events were more commonly reported for ABC/3TC/ZDV + EFV than for ABC/3TC/ZDV ( 15 % vs. 6 % ) . Improvements in total cholesterol , low-density lipoprotein cholesterol , and triglycerides were observed in the ABC/3TC/ZDV group . Virologic failure occurred in 22 patients during induction and in 24 patients ( 16 in ABC/3TC/ZDV group and 8 in ABC/3TC/ZDV + EFV group ; P = 0.134 ) during maintenance . A greater proportion of patients receiving ABC/3TC/ZDV than ABC/3TC/ZDV + EFV reported perfect adherence at week 96 ( 88.8 % vs. 79.6 % ; P = 0.057 ) . Conclusions : After induction with ABC/3TC/ZDV + EFV , simplification to ABC/3TC/ZDV alone maintained virologic control and immunologic response , reduced fasting lipids and ART-associated adverse events , and improved adherence Background : Regimens with two nucleoside analogue reverse transcriptase inhibitors ( NRTI ) plus tenofovir DF have been associated with a high failure rate when administered as first line therapy . Little is known about patients with undetectable viral loads who are switched to these regimens . Methods : A post-hoc review of the virological outcomes at 24 weeks of patients who switched from a successful ( < 50 copies/ml ) highly active antiretroviral therapy regimen to a tenofovir plus two NRTI combination . Results : Fifty-five patients started a two NRTI plus tenofovir regimen mostly because of previous toxicity/intolerance of the original drugs ( 74 % ) . After 24 weeks , only 17 patients ( 31 % ) remained virologically suppressed . Patients with a regimen including a didanosine plus tenofovir-based regimen had significantly poorer outcomes than those on other combinations ( success rate 5 versus 47.1 % , P = 0.001 ) . In contrast , patients on a regimen including zidovudine plus tenofovir showed a trend towards a better outcome ( 75 versus 27 % , P = 0.083 ) . Multivariate analysis confirmed the combination of didanosine plus tenofovir as the only variable associated with a higher rate of failure ( odds ratio 17.7 ; 95 % confidence interval 2.1–147 ; P = 0.007 ) . Patients with previous reverse transcriptase mutations presented virological failure in all cases . At failure a new pattern , including the K65R mutation with M184V or thymidine analogue mutations , was observed . Conclusions : Even in patients with suppressed viraemia , a two NRTI plus tenofovir regimen is associated with a high virological failure rate , but significant variations are found depending on the nucleosides included BACKGROUND Triple nucleoside reverse transcriptase inhibitor regimens have advantages as first-line antiretroviral therapy ( ART ) , avoiding hepatotoxicity and interactions with anti-tuberculosis therapy , and sparing two drug classes for second-line ART . Concerns exist about virological potency ; efficacy has not been assessed in Africa . METHODS A safety trial comparing nevirapine with abacavir was conducted in two Ug and an Development of Antiretroviral Therapy in Africa ( DART ) centres : 600 symptomatic antiretroviral-naïve HIV-infected adults with CD4 counts < 200 cells/microL were r and omized to zidovudine/lamivudine plus abacavir or nevirapine ( placebo-controlled to 24-week primary toxicity endpoint , and then open-label ) . Documented World Health Organization ( WHO ) stage 4 events were independently review ed and plasma HIV-1 RNA assayed retrospectively . Exploratory efficacy analyses are intention-to-treat . RESULTS The median pre-ART CD4 count was 99 cells/microL , and the median pre-ART viral load was 284 600 HIV-1 RNA copies/mL. A total of 563 participants ( 94 % ) completed 48 weeks of follow-up , 25 ( 4 % ) died and 12 ( 2 % ) were lost to follow-up . The r and omized drug was substituted in 21 participants ( 7 % ) receiving abacavir vs. 34 ( 11 % ) receiving nevirapine ( P=0.09 ) . At 48 weeks , 62 % of participants receiving abacavir vs. 77 % of those receiving nevirapine had viral loads < 50 copies/mL ( P<0.001 ) , and mean CD4 count increases from baseline were + 147 vs. + 173 cells/microL , respectively ( P=0.006 ) . Nine participants ( 3 % ) receiving abacavir vs. 16 ( 5 % ) receiving nevirapine died [ hazard ratio ( HR ) 0.55 ; 95 % confidence interval ( CI ) 0.24 - 1.25 ; P=0.15 ] ; 20 receiving abacavir vs. 32 receiving nevirapine developed new or recurrent WHO 4 events or died ( HR=0.60 ; 95 % CI 0.34 - 1.05 ; P=0.07 ) and 48 receiving abacavir vs. 68 receiving nevirapine developed new or recurrent WHO 3 or 4 events or died ( HR=0.67 ; 95 % CI 0.46 - 0.96 ; P=0.03 ) . Seventy-one participants ( 24 % ) receiving abacavir experienced 91 grade 4 adverse events compared with 130 events in 109 participants ( 36 % ) on nevirapine ( P<0.001 ) . CONCLUSIONS The clear virological/immunological superiority of nevirapine over abacavir was not reflected in clinical outcomes over 48 weeks . The inability of CD4 cell count/viral load to predict initial clinical treatment efficacy is unexplained and requires further evaluation Objective : To compare alternative class-sparing antiretroviral regimens in treatment-naive subjects . Design : Open-label , multicenter , r and omized trial of up to 3 consecutive treatment regimens over 96 weeks . Methods : Two hundred ninety-one subjects received abacavir ( ABC ) and lamivudine and efavirenz ( nonnucleoside reverse transcriptase inhibitors [ NNRTIs ] ) , ritonavir-boosted amprenavir ( protease inhibitor [ PI ] ) , or stavudine ( nucleoside reverse transcriptase inhibitor [ NRTI ] ) by r and om assignment . The primary end points were the percentages of subjects with plasma HIV-1 RNA levels < 400 copies/mL and time to treatment failure over 96 weeks . Results : Ninety percent of subjects completed 96 weeks of follow-up , and 79 % remained on study treatment . At week 96 , there were no differences between arms in the percentages of subjects with plasma HIV-1 RNA levels < 400 and < 50 copies/mL , mean changes in plasma HIV-1 RNA levels , time to treatment failure , time to first or second virologic failure , or CD4 + cell counts . The NNRTI arm had a greater percentages of subjects with RNA levels ≤50 copies/mL at weeks 24 and 48 and a greater overall duration of plasma HIV-1 RNA levels < 400 copies/mL. Three subjects in the NNRTI arm had treatment failure on their first regimen and switched therapy compared with 16 in the NRTI arm and 13 in the PI arm . Twenty-one subjects had hypersensitivity reactions attributed to ABC ( 7.3 % ) . Fewer drugs were used by subjects in the NNRTI arm , and fewer subjects in the NNRTI arm used 3 drug classes . Conclusions : All treatment regimens demonstrated excellent 96-week results . Secondary analyses favored the NNRTI regimen over the PI and NRTI regimens BACKGROUND HIV antiretroviral therapy ( ART ) is often managed without routine laboratory monitoring in Africa ; however , the effect of this approach is unknown . This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa . METHODS In this open , non-inferiority trial in three centres in Ug and a and one in Zimbabwe , 3321 symptomatic , ART-naive , HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were r and omly assigned to laboratory and clinical monitoring ( LCM ; n=1659 ) or clinical ly driven monitoring ( CDM ; n=1662 ) by a computer-generated list . Haematology , biochemistry , and CD4-cell counts were done every 12 weeks . In the LCM group , results were available to clinicians ; in the CDM group , results ( apart from CD4-cell count ) could be requested if clinical ly indicated and grade 4 toxicities were available . Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups , or CD4 count less than 100 cells per microL ( LCM only ) . Co- primary endpoints were new WHO stage 4 HIV events or death , and serious adverse events . Non-inferiority was defined as the upper 95 % confidence limit for the hazard ratio ( HR ) for new WHO stage 4 events or death being no greater than 1.18 . Analyses were by intention to treat . This study is registered , number IS RCT N13968779 . FINDINGS Two participants assigned to CDM and three to LCM were excluded from analyses . 5-year survival was 87 % ( 95 % CI 85 - 88 ) in the CDM group and 90 % ( 88 - 91 ) in the LCM group , and 122 ( 7 % ) and 112 ( 7 % ) participants , respectively , were lost to follow-up over median 4.9 years ' follow-up . 459 ( 28 % ) participants receiving CDM versus 356 ( 21 % ) LCM had a new WHO stage 4 event or died ( 6.94 [ 95 % CI 6.33 - 7.60 ] vs 5.24 [ 4.72 - 5.81 ] per 100 person-years ; absolute difference 1.70 per 100 person-years [ 0.87 - 2.54 ] ; HR 1.31 [ 1.14 - 1.51 ] ; p=0.0001 ) . Differences in disease progression occurred from the third year on ART , whereas higher rates of switch to second-line treatment occurred in LCM from the second year . 283 ( 17 % ) participants receiving CDM versus 260 ( 16 % ) LCM had a new serious adverse event ( HR 1.12 [ 0.94 - 1.32 ] ; p=0.19 ) , with anaemia the most common ( 76 vs 61 cases ) . INTERPRETATION ART can be delivered safely without routine laboratory monitoring for toxic effects , but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment . FUNDING UK Medical Research Council , the UK Department for International Development , the Rockefeller Foundation , GlaxoSmithKline , Gilead Sciences , Boehringer-Ingelheim , and Abbott Laboratories |
2,189 | 26,932,981 | Conclusion : There is insufficient research to differentiate between the user experience of different transtibial liners .
Clinical relevance The available evidence suggests that the user experience of commonly reported problems ( e.g. sweating ) may be very similar between different liners . | Background : The liner is an integral part of a transtibial prosthesis design ed to protect the residual limb , enhance comfort and provide suspension .
Literature is difficult to interpret and use given the variety of interventions , outcome measures and method design s. Critical appraisal and synthesis of the evidence is needed to help inform decisions about liner prescription based on the user experience .
Objectives : To critically appraise and synthesis e research describing the user experience of transtibial prosthetic liners . | BACKGROUND Transtibial amputees encounter stairs and steps during their daily activities . The excessive pressure between residual limb/socket may reduce the walking capability of transtibial prosthetic users during ascent and descent on stairs . The purpose s of the research were to evaluate the interface pressure between Dermo ( shuttle lock ) and Seal-In X5 ( prosthetic valve ) interface systems during stair ascent and descent , and to determine their satisfaction effects on users . METHODS Ten amputees with unilateral transtibial amputation participated in the study . Interface pressure was recorded with F-socket transducer ( 9811E ) during stair ascent and descent at self-selected speed . Each participant filled in a question naire about satisfaction and problems encountered with the use of the two interface systems . FINDINGS The result ant mean peak pressure ( kPa ) was significantly lower for the Dermo interface system compared to that of the Seal-In X5 interface system at the anterior , posterior and medial regions during stair ascent ( 63.14 vs. 80.14 , 63.14 vs. 90.44 , 49.21 vs. 66.04 , respectively ) and descent ( 67.11 vs. 80.41 , 64.12 vs. 88.24 , 47.33 vs. 65.11 , respectively ) . Significant statistical difference existed between the two interface systems in terms of satisfaction and problems encountered ( P<0.05 ) . INTERPRETATION The Dermo interface system caused less pressure within the prosthetic socket compared to the Seal-In X5 interface system during stair negotiation . The qualitative survey also showed that the prosthesis users experienced fewer problems and increased satisfaction with the Dermo interface system OBJECTIVE To investigate the effects of 3 dissimilar suspension systems on participants ' satisfaction and perceived problems with their prostheses . DESIGN Question naire survey . SETTING A medical and engineering research center and a university biomedical engineering department . PARTICIPANTS Persons with unilateral transtibial amputation ( N=243 ) , using prostheses with polyethylene foam liner , silicone liner with shuttle lock , and seal-in liner . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Descriptive analyses were performed on the demographic information , satisfaction , and prosthesis-related problems of the study participants . RESULTS The results showed significant differences between the 3 groups regarding the degree of satisfaction and perceived problems with the prosthetic device . Analyses of the individual items revealed that the study participants were more satisfied with the seal-in liner and experienced fewer problems with this liner . The silicone liner with shuttle lock and seal-in liner users reported significant differences in maintenance time compared with the polyethylene foam liner . Users of the silicone liner with shuttle lock experienced more sweating , while those who used the seal-in liner had greater problems with donning and doffing the device . CONCLUSIONS The results of the survey provide a good indication that prosthetic suspension is improved with the seal-in liner as compared with the polyethylene foam liner and silicone liner with shuttle lock . However , further prospect i ve studies are needed to investigate which system provides the most comfort and the least problems for participants Background The suction sockets that are commonly prescribed for transtibial amputees are believed to provide a better suspension than the pin/lock systems . Nevertheless , their effect on amputees ’ gait performance has not yet been fully investigated . The main intention of this study was to underst and the potential effects of the Seal-in ( suction ) and the Dermo ( pin/lock ) suspension systems on amputees ’ gait performance . Methodology /Principal Findings Ten unilateral transtibial amputees participated in this prospect i ve study , and two prostheses were fabricated for each of them . A three-dimensional motion analysis system was used to evaluate the temporal-spatial , kinematics and kinetics variables during normal walking . We also asked the participants to complete some part of Prosthesis Evaluation Question naire ( PEQ ) regarding their satisfaction and problems with both systems . The results revealed that there was more symmetry in temporal-spatial parameters between the prosthetic and sound limbs using the suction system . However , the difference between two systems was not significant ( p<0.05 ) . Evaluation of kinetic data and the subjects ’ feedback showed that the participants had more confidence using the suction socket and the sockets were more fit for walking . Nevertheless , the participants had more complaints with this system due to the difficulty in donning and doffing . Conclusion It can be concluded that even though the suction socket could create better suspension , fit , and gait performance , overall satisfaction was higher with the pin/lock system due to easy donning and doffing of the prosthesis . Trial Registration i rct .ir I RCT For this r and omized crossover trial , we compared two common transtibial socket suspension systems : the Alpha liner with distal locking pin and the Pe-Lite liner with neoprene suspension sleeve . Our original hypotheses asserted that increased ambulatory activity , wear time , comfort , and satisfaction would be found with the elastomeric suspension system . Thirteen subjects completed the study . Following 2.5-month accommodation to each condition , ambulatory activity was recorded ( steps/minute for 2 weeks ) , and subjects completed three question naires specific to prosthesis use and pain : the Prosthesis Evaluation Question naire ( PEQ ) , a Brief Pain Inventory ( BPI ) excerpt , and the Socket Comfort Score ( SCS ) . Upon completion , subjects selected their favored system for continued use . Ten subjects preferred the Pe-Lite and three the Alpha . Subjects spent 82 % more time wearing the Pe-Lite and took 83 % more steps per day . Ambulatory intensity distribution did not differ between systems . No statistically significant differences were found in question naire results . Subject feedback for each system was both positive and negative BACKGROUND The interface pressure between the residual limb and prosthetic socket has a significant effect on an amputee 's satisfaction and comfort . Liners provide a comfortable interface by adding a soft cushion between the residual limb and the socket . The Dermo and the Seal-In X5 liner are two new interface systems and , due to their relative infancy , very little are known about their effect on patient satisfaction . The aim of this study was to compare the interface pressure with these two liners and their effect on patient satisfaction . METHODS Nine unilateral transtibial amputees participated in the study . Two prostheses were fabricated for each amputee , one with the Seal-In liner and one with the Dermo liner . Interface pressure was measured at the anterior , posterior , medial and lateral regions during walking on the level ground . Each subject filled in a Prosthetic Evaluation Question naire ( PEQ ) regarding the satisfaction with the two liners . Findings The mean peak pressures with the Seal-In liner was 34.0 % higher at the anterior , 24.0 % higher at the posterior and 7.0 % higher at the medial regions of the socket ( P=0.008 , P=0.046 , P=0.025 ) than it was with the Dermo Liner . There were no significant differences in the mean peak pressures between the two liners at the lateral regions . In addition , significant difference was found between the two liners both for satisfaction and problems ( P<0.05 ) . Interpretation There was less interface pressure between the socket and the residual limb with the Dermo liner . The results indicated that the Dermo liner provides more comfort in the socket than the Seal-In liner OBJECTIVE To investigate the effect of a vacuum-assisted socket suspension system as compared with pin suspension on lower extremity amputees . DESIGN R and omized crossover with 3-week acclimation . SETTING Household , community , and laboratory environments . PARTICIPANTS Unilateral , transtibial amputees ( N=20 enrolled , N=5 completed ) . INTERVENTIONS ( 1 ) Total surface-bearing socket with a vacuum-assisted suspension system ( VASS ) , and ( 2 ) modified patellar tendon-bearing socket with a pin lock suspension system . MAIN OUTCOME MEASURES Activity level , residual limb volume before and after a 30-minute treadmill walk , residual limb pistoning , and Prosthesis Evaluation Question naire . RESULTS Activity levels were significantly lower while wearing the vacuum-assisted socket suspension system than the pin suspension ( P=.0056 ; 38,000 ± 9,000 steps per 2 wk vs 73,000 ± 18,000 steps per 2 wk , respectively ) . Residual limb pistoning was significantly less while wearing the vacuum-assisted socket suspension system than the pin suspension ( P=.0021 ; 1 ± 3 mm vs 6 ± 4 mm , respectively ) . Treadmill walking had no effect on residual limb volume . In general , participants ranked their residual limb health higher , were less frustrated , and cl aim ed it was easier to ambulate while wearing a pin suspension compared with the VASS . CONCLUSIONS The VASS result ed in a better fitting socket as measured by limb movement relative to the prosthetic socket ( pistoning ) , although the clinical relevance of the small but statistically significant difference is difficult to discern . Treadmill walking had no effect , suggesting that a skilled prosthetist can control for daily limb volume fluctuations by using conventional , nonvacuum systems . Participants took approximately half as many steps while wearing the VASS which , when coupled with their subjective responses , suggests a preference for the pin suspension system Objective The objectives of this study were to compare the effects of a newly design ed magnetic suspension system with that of two existing suspension methods on pistoning inside the prosthetic socket and to compare satisfaction and perceived problems among transtibial amputees . Design In this prospect i ve study , three lower limb prostheses with three different suspension systems were fabricated for ten transtibial amputees . The participants used each of the three prostheses for 1 mo in r and om order . Pistoning inside the prosthetic socket was measured by motion analysis system . The Prosthesis Evaluation Question naire was used to evaluate satisfaction and perceived problems with each suspension system . Results The lowest pistoning motion was found with the suction system compared with the other two suspension systems ( P < 0.05 ) . The new suspension system showed peak pistoning values similar to that of the pin lock system ( P = 0.086 ) . The results of the question naire survey revealed significantly higher satisfaction rates with the new system than with the other two systems in donning and doffing , walking , uneven walking , stair negotiation , and overall satisfaction ( P < 0.05 ) . Conclusions The new suspension system has the potential to be used as an alternative to the available suspension systems . The pistoning motion was comparable to that of the other two systems . The new system showed compatible prosthetic suspension with the other two systems ( suction and pin lock ) . The satisfaction with donning and doffing was high with the magnetic system . Moreover , the subjects reported fewer problems with the new system A clinical trial was conducted to evaluate the efficiency of ICEROSS on r and omly selected 46 male transtibial amputees . After rejection , only 27 ( 58.69 % ) amputees volunteered for various stages of the ICEROSS trial . All 27 were categorized into Group A-persons in employment ( n = 16 ) and Group B-persons out of employment or economically inactive ( n = 11 ) . The study was conducted on the basis of question naire information , clinical examination and objective tests . The pre- and post-ICEROSS status were compared between the groups . Group A was younger and did better . Trauma was the main cause of amputation . There were certain changes of the stump before and after ICEROSS . The amputees with ICEROSS suspension performed better and had improved mobility in Group A. At the workplace , dynamic activities were less than the static activities ( p < 0.001 ) and there were overall improvements in comfort and performance of amputees with ICEROSS Trans-tibial amputees with different indications for amputation often have stump problems . Many active amputees have limits in daily life and sports activities because of pressure ulcers , friction , allergic dermatitis or volume changes . Many methods and material s have been tried to make a well-fitted socket . A new polyurethane concept had been design ed with a shock absorbing effect . The purpose of this prospect i ve study was to compare a conventional suspension with a polyurethane concept with regard to the amputees ' satisfaction , socket comfort , physical capacity and to analyse the long-term effect . The total material includes 29 unilateral transtibial amputees . They answered a question naire after 2 months use of the polyurethane concept and were interviewed after 3 and 5 years . After 3 years 22 amputees and after 5 years 20 amputees used the polyurethane concept . Gait was registered in 7 amputees . Speed and symmetry index ( SI ) for temporal , stride and kinematics variables were used to evaluate gait . The amputees reported that the polyurethane concept was better or much better in physical capacity in 117 ( 67 % ) and socket comfort was better or much better in 119 ( 82 % ) compared with the conventional suspension . There was no obvious symmetry difference in gait variables in speed , step length , step time or single support or in kinematics knee variables . The amputees tended to walk faster , decrease in symmetry in temporal and stride variables and increase in symmetry in kinematics variables with the polyurethane concept . After 5 years 6 had died and 20 amputees of the surviving 23 used the polyurethane concept . Conclusions : The polyurethane concept increased comfort considerably and physical activity increased when the trans-tibial amputees changed from conventional suspension . Gait registration was not useful to evaluate the amputees ' satisfaction or socket comfort The ICEX ® system ( Ossur , Icel and ) , allows a socket to be manufactured directly onto the stump and is thought to provide improved comfort due to better pressure distribution whilst being easier to fit and manufacture . The aims of this project were to a ) compare gait performance by measuring several gait characteristics , b ) compare production and fitting times , c ) investigate financial implication s and d ) attempt to gauge the amputees ’ subjective opinions of socket comfort . A r and omised , controlled trial was conducted on 27 trans-tibial amputees with an existing patellar tendon bearing ( PTB ) socket on the Endolite ™ system ( Chas A. Blatchford , UK ) . Twenty one ( 21 ) subjects completed the study . Of these , 10 in the control group received new PTB sockets while 11 in the experimental group received ICEX ® . Gait analysis wearing existing sockets was performed and kinetic data obtained from a force plate . This was repeated with the new sockets after a 6 week period of adjustment . Mann-Whitney tests were used in statistical evaluations with a significance level of 5 % . Subjects were asked to score their prosthesis for comfort using the Socket Comfort Score ( Hanspal et al. , 2003 ) and the frequency of visits for socket adjustments over a three-month period post-delivery of the sockets was recorded . This study demonstrates no significant difference in any of the gait parameters measured . Though the time required to manufacture a PTB prosthesis was found to be considerably longer than the ICEX ® , the overall cost for producing the ICEX ® was significantly greater . Subjects showed only minor comfort preference for the ICEX ® design and there was no significant difference in the mean number of visits for socket adjustments . In view of the considerable additional cost of providing ICEX ® and the lack of evidence of improvement in any parameter tested , the routine provision of ICEX ® prostheses to unselected trans-tibial amputees can not be recommended |
2,190 | 28,886,607 | The measures of impact of registries were multifarious and included change in processes of care , quality of care , treatment outcomes , adherence to guidelines and survival .
Despite the large number of published articles using data derived from CQRs , few have rigorously evaluated the impact of the registry as an intervention on improving health outcomes .
Those that have evaluated this impact have mostly found a positive impact on healthcare processes and outcomes . | BACKGROUND Clinical quality registries ( CQRs ) are playing an increasingly important role in improving health outcomes and reducing health care costs .
CQRs are established with the purpose of monitoring quality of care , providing feedback , benchmarking performance , describing pattern of treatment , reducing variation and as a tool for conducting research .
OBJECTIVES To synthesis e the impact of clinical quality registries ( CQRs ) as an ' intervention ' on ( I ) mortality/survival ; ( II ) measures of outcome that reflect a process or outcome of health care ; ( III ) health care utilisation ; and ( IV ) healthcare-related costs . | CONTEXT A rigorous evaluation of continuous quality improvement ( CQI ) in medical practice has not been carried out on a national scale . OBJECTIVE To test whether low-intensity CQI interventions can be used to speed the national adoption of 2 coronary artery bypass graft ( CABG ) surgery process-of-care measures : preoperative beta-blockade therapy and internal mammary artery ( IMA ) grafting in patients 75 years or older . DESIGN , SETTING , AND PARTICIPANTS Three hundred fifty-nine academic and nonacademic hospitals ( treating 267 917 patients using CABG surgery ) participating in the Society of Thoracic Surgeons National Cardiac Data base between January 2000 and July 2002 were r and omized to a control arm or to 1 of 2 groups that used CQI interventions design ed to increase use of the process-of-care measures . INTERVENTION Each intervention group received measure-specific information , including a call to action to a physician leader ; educational products ; and periodic longitudinal , nationally benchmarked , site-specific feedback . MAIN OUTCOME MEASURE Differential incorporation of the targeted care processes into practice at the intervention sites vs the control sites , assessed by measuring preintervention ( January-December 2000)/postintervention ( January 2001-July 2002 ) site differences and by using a hierarchical patient-level analysis . RESULTS From January 2000 to July 2002 , use of both process measures increased nationally ( beta-blockade , 60.0%-65.6 % ; IMA grafting , 76.2%-82.8 % ) . Use of beta-blockade increased significantly more at beta-blockade intervention sites ( 7.3 % [ SD , 12.8 % ] ) vs control sites ( 3.6 % [ SD , 11.5 % ] ) in the preintervention/postintervention ( P = .04 ) and hierarchical analyses ( P<.001 ) . Use of IMA grafting also tended to increase at IMA intervention sites ( 8.7 % [ SD , 17.5 % ] ) vs control sites ( 5.4 % [ SD,15.8 % ] ) ( P = .20 and P = .11 for preintervention/postintervention and hierarchical analyses , respectively ) . Both interventions tended to have more impact at lower-volume CABG sites ( for interaction : P = .04 for beta-blockade ; P = .02 for IMA grafting ) . CONCLUSIONS A multifaceted , physician-led , low-intensity CQI effort can improve the adoption of care processes into national practice within the context of a medical specialty society infrastructure BACKGROUND The adherence to evidence -based treatment guidelines for acute myocardial infa rct ion ( AMI ) is still suboptimal . Therefore , we design ed a study to evaluate the effects of a collaborative quality improvement ( QI ) intervention on the adherence to AMI guidelines . The intervention used a national web-based quality registry to generate local and regular real-time performance feedback . METHODS A 12-month baseline measurement of the adherence rates was retrospectively collected , comprising the period July 1 , 2001 , through June 30 , 2002 . During the intervention period of November 1 , 2002 , through April 30 , 2003 , multidisciplinary teams from 19 nonr and omized intervention hospitals were subjected to a multifaceted QI-oriented intervention . Another 19 hospitals , unaware of their status as controls , were matched to the intervention hospitals . During the postintervention measurement period of May 1 , 2003 , through April 30 , 2004 , a total of 6726 consecutive patients were included at the intervention ( n = 3786 ) and control ( n = 2940 ) hospitals . The outcome measures comprised 5 Swedish national guideline -derived quality indicators , compared between baseline and postintervention levels in the control and QUICC intervention hospitals . RESULTS In the control and QI intervention hospitals , the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4 % vs 12.6 % ( P = .002 ) , lipid-lowering therapy 2.3 % vs 7.2 % ( P = .065 ) , clopidogrel 26.3 % vs 41.2 % ( P = .010 ) , heparin/low-molecular weight heparin 5.3 % vs 16.3 % ( P = .010 ) , and coronary angiography 6.2 % vs 16.8 % ( P = .027 ) , respectively . The number of QI intervention hospitals reaching a treatment level of at least 70 % in 4 or 5 of the 5 indicators was 15 and 5 , respectively . In the control group , no hospital reached 70 % or more in just 4 of the 5 indicators . CONCLUSIONS By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback , major improvements in the adherence to national AMI guidelines can be achieved Background — Adherence to evidence -based guidelines for treatment of stroke or transient ischemic attack is suboptimal . We sought to establish whether participation in Get With the Guidelines –Stroke was associated with improvements in adherence . Methods and Results — This prospect i ve , nonr and omized , national quality improvement program measured adherence to guideline recommendations in 322 847 hospitalized patients discharged with a diagnosis of ischemic stroke or transient ischemic attack . A volunteer sample of 790 US academic and community hospitals participated from 2003 through 2007 . The main outcome measures were change in adherence over time to 7 prespecified performance measures and a composite measure ( total number of interventions provided in eligible patients divided by total number of care opportunities among eligible patients ) . Generalized estimating equations were used to identify factors associated with improvement . Participation in Get With the Guidelines –Stroke was associated with improvements in the 7 individual and 1 composite measures from baseline to the fifth year : intravenous thrombolytics ( 42.09 % versus 72.84 % ) , early antithrombotics ( 91.46 % versus 97.04 % ) , deep vein thrombosis prophylaxis ( 73.79 % versus 89.54 % ) , discharge antithrombotics ( 95.68 % versus 98.88 % ) , anticoagulation for atrial fibrillation ( 95.03 % versus 98.39 % ) , lipid treatment for low-density lipoprotein > 100 mg/dL ( 73.63 % versus 88.29 % ) , smoking cessation ( 65.21 % versus 93.61 % ) , and composite ( 83.52 % versus 93.97 % ) ( P<0.0001 for all comparisons ) . Multivariate analysis showed that time in Get With the Guidelines –Stroke was associated with a 1.18-fold yearly increase in the odds of fulfilling care opportunities that was independent of secular trends . Conclusions — Get With the Guidelines –Stroke participation was associated with increased adherence to all stroke performance measures . Markedly improved stroke care was seen in all hospitals regardless of size , geography , and teaching status Background and Purpose — Limited information is available on stroke management in developing countries . An accurate monitoring of quality of stroke care will become crucial , particularly with the emerging paradigm of pay-for-performance . Our aim was to explore the feasibility of measuring st and ardized indicators of quality of ischemic stroke care in acute care facilities in Argentina . Methods — ReNACer is a prospect i ve , multicenter , countrywide , stroke registry comprising 74 academic and nonacademic institutions in Argentina . The registry includes patient-level information on demography , clinical characteristics , diagnostic procedures , treatment , and the selected key performance indicators of quality of ischemic stroke care ( access to thrombolysis or aspirin use in the acute setting , admission to design ated stroke units , length of stay , risk-adjusted in-hospital pneumonia , risk-adjusted in-hospital mortality , discharge on antithrombotics , and antihypertensive agents ) . Results — We included 1991 patients with ischemic stroke from 74 institutions in Argentina between November 2004 and October 2006 . Seventy-nine per cent of the patients were prescribed antithrombotic therapy within 48 hours of admission , but only 1 % received thrombolytics . No more than 5.7 % were admitted to stroke units . In-hospital pneumonia was diagnosed in 14.3 % of the patients and was higher in nonacademic facilities ( 16.4 % versus 11.4 % , P<0.02 ) . The overall adjusted in-hospital mortality was 9.1 % , also higher in nonacademic hospitals ( 10.6 % versus 7.1 % , P<0.008 ) . At discharge , antithrombotics were prescribed in 90.2 % and antihypertensive agents in 63.6 % of the patients . Conclusions — In ReNACer , there was a limited access to stroke units and thrombolytics , and a relatively high incidence of in-hospital pneumonia . Differences in stroke care were observed between academic and nonacademic institutions . There is an urgent need to develop national stroke programs in Argentina Cardiovascular disease remains the primary cause of mortality , and a major cause of disability in the developed world.1 This significant burden necessitates ongoing improvements in patient management , to minimize the impact of cardiovascular conditions on both patients and healthcare systems . These improvements in cardiovascular care are promoted by an evidence -based approach , shaped by comprehensive clinical guidelines . The scientific basis of recommendations is an important feature of clinical guidelines , and influences the degree to which they are followed in clinical practice .2 Recent studies have assigned the highest evidence grading to r and omized controlled trials ( RCTs ) that are clinical ly important , and representative of the clinical population covered by the guideline recommendation .3 For example , this highest grading was assigned to a recommendation based on a meta- analysis of RCTs showing low-dose diuretics to be the most effective first-line treatment for cardiovascular event prevention in hypertensive patients . This study review ed data from 42 RCTs which were , crucially , representative of the population that the recommendation was made for ( i.e. hypertensive patients ) .3,4 The importance of the applicability of evidence to recommendations highlights the need to consider evidence from clinical ly relevant situations , not all of which have been assessed by RCTs . This evidence can originate from expert consensus , as well as non-r and omized prospect i ve studies . Although generally providing a lower evidence -level than RCTs , 3,5 observational studies can make an important contribution to the evidence base when the study outcomes are clinical ly important , and the population s involved are representative . Indeed , information from several registries was considered in the recent American Heart Association Acute Coronary Care in the Elderly Scientific Statement.6 Non-r and omized prospect i ve registries document the treatment and outcomes for consecutive patients in clinical practice . Therefore , data are gained from a ‘ real-world ’ selection of patients , many of whom would be excluded from RCTs , OBJECTIVE To estimate the effect of multicentre surveillance for nosocomial infections on patients ' risk of surgical site infection ( SSI ) . DESIGN Prospect i ve multi-centre cohort study , from January 1996 to December 2000 . SETTING Acute care hospitals in The Netherl and s. STUDY PARTICIPANTS All 50 hospitals performing surveillance for one of seven selected procedures in the Dutch surveillance network for nosocomial infections PREZIES were invited . Thirty-seven hospitals participated ( 74 % ) and provided information on 21 920 operations , after which 885 ( 4 % ) SSI occurred . INTERVENTIONS The surveillance comprised the following : Development of surveillance methodology by multidisciplinary team ; use of a st and ardized registration protocol and software ; regular training of data collectors ; anonymous inter-hospital comparison of infection rates and feedback of results ; appointment of one contact person per hospital , responsible for data collection ; and dissemination of results to other health care professionals . Regular discussion of both successful and failing prevention strategies that had been instituted based on the surveillance results . OUTCOME MEASURE Risk of SSI . RESULTS The risk of infection was reduced for patients who had an operation during the fourth surveillance year ( RR = 0.69 ; 95 % confidence interval ( CI ) = 0.52 - 0.89 ) and decreased further for patients operated on during the fifth surveillance year ( RR = 0.43 ; CI = 0.24 - 0.76 ) as compared with patients who underwent surgery within one year of the start of surveillance in their hospital . No significant risk reduction was observed for patients operated on during the second and third surveillance years . CONCLUSION Surveillance , supported by participation in a surveillance network , reduced the risk of SSI in surgical patients registered in the Dutch surveillance network PREZIES . Our results suggest that infection control teams need to be perseverant and that surveillance programmes should be given time before evaluation Background — A treatment gap exists between heart failure ( HF ) guidelines and the clinical care of patients . The Registry to Improve the Use of Evidence -Based Heart Failure Therapies in the Outpatient Setting ( IMPROVE HF ) prospect ively tested a multidimensional practice -specific performance improvement intervention on the use of guideline -recommended therapies for HF in outpatient cardiology practice s. Methods and Results — Performance data were collected in a r and om sample of HF patients from 167 US outpatient cardiology practice s at baseline , longitudinally after intervention at 12 and 24 months , and in single-point-in-time patient cohorts at 6 and 18 months . Participants included 34 810 patients with reduced left ventricular ejection fraction ( ≤35 % ) and chronic HF or previous myocardial infa rct ion . To quantify guideline adherence , 7 quality measures were assessed . Interventions included clinical decision support tools , structured improvement strategies , and chart audits with feedback . The performance improvement intervention result ed in significant improvements in 5 of 7 quality measures at the 24-month assessment compared with baseline : & bgr;-blocker ( 92.2 % versus 86.0 % , + 6.2 % ) , aldosterone antagonist ( 60.3 % versus 34.5 % , + 25.1 % ) , cardiac resynchronization therapy ( 66.3 % versus 37.2 % , + 29.9 % ) , implantable cardioverter-defibrillator ( 77.5 % versus 50.1 % , + 27.4 % ) , and HF education ( 72.1 % versus 59.5 % , + 12.6 % ) ( each P<0.001 ) . There were no statistically significant improvements in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use or anticoagulation for atrial fibrillation . Sensitivity analyses at the patient level and limited to patients with both baseline and 24-month quality measure data yielded similar results . Improvements in the single-point-in-time cohorts were smaller , and there were no concurrent control practice s. Conclusions — The Registry to Improve the Use of Evidence -Based Heart Failure Therapies in the Outpatient Setting , a defined and scalable practice -specific performance improvement intervention , was associated with substantial improvements in the use of guideline -recommended therapies in eligible patients with HF in outpatient cardiology practice s. Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00303979 BACKGROUND This study tested the effects of two organizational support processes , the provision of financial incentives for superior clinical performance and the availability of a patient ( smoker ) registry and proactive telephone support system for smoking cessation , on provider adherence to accepted practice guidelines and associated patient outcomes . METHODS Forty clinics of a large multispecialty medical group practice providing primary care services were r and omly allocated to study conditions . Fifteen clinics each were assigned to the experimental conditions " control " ( distribution of printed versions of smoking cessation guidelines ) and " incentive " ( financial incentive pay-out for reaching preset clinical performance targets ) . Ten clinics were r and omized to receive financial incentives combined with access to a central ized patient registry and intervention system ( " registry " ) . Main outcome measures were adherence to smoking cessation clinical practice guidelines and patients ' smoking cessation behaviors . RESULTS Patients ' tobacco use status was statistically significant ( P < 0.01 ) more frequently identified in clinics with the opportunity for incentives and access to a registry than in clinics in the control condition . Patients visiting registry clinics accessed counseling programs statistically significantly more often ( P < 0.001 ) than patients receiving care in the control condition . Other endpoints did not statistically significantly differ between the experimental conditions . CONCLUSIONS The impact of financial incentives and a patient registry/intervention system in improving smoking cessation clinical practice s and patient behaviors was mixed . Additional research is needed to identify conditions under which such organizational support processes result in significant health care quality improvement and warrant the investment OBJECTIVE To provide reliable risk-adjusted morbidity and mortality rates after major surgery to the 123 Veterans Affairs Medical Centers ( VAMCs ) performing major surgery , and to use risk-adjusted outcomes in the monitoring and improvement of the quality of surgical care to all veterans . SUMMARY BACKGROUND DATA Outcome -based comparative measures of the quality of surgical care among surgical services and surgical subspecialties have been elusive . METHODS This study included prospect i ve assessment of presurgical risk factors , process of care during surgery , and outcomes 30 days after surgery on veterans undergoing major surgery in 123 medical centers ; development of multivariable risk-adjustment models ; identification of high and low outlier facilities by observed-to-expected outcome ratios ; and generation of annual reports of comparative outcomes to all surgical services in the Veterans Health Administration ( VHA ) . RESULTS The National VA Surgical Quality Improvement Program ( NSQIP ) data base includes 417,944 major surgical procedures performed between October 1 , 1991 , and September 30 , 1997 . In FY97 , 11 VAMCs were low outliers for risk-adjusted observed-to-expected mortality ratios ; 13 VAMCs were high outliers for risk-adjusted observed-to-expected mortality ratios . Identification of high and low outliers by unadjusted mortality rates would have ascribed an outlier status incorrectly to 25 of 39 hospitals , an error rate of 64 % . Since 1994 , the 30-day mortality and morbidity rates for major surgery have fallen 9 % and 30 % , respectively . CONCLUSIONS Reliable , valid information on patient presurgical risk factors , process of care during surgery , and 30-day morbidity and mortality rates is available for all major surgical procedures in the 123 VAMCs performing surgery in the VHA . With this information , the VHA has established the first prospect i ve outcome -based program for comparative assessment and enhancement of the quality of surgical care among multiple institutions for several surgical subspecialties . Key features to the success of the NSQIP are the support of the surgeons who practice in the VHA , consistent clinical definitions and data collection by dedicated nurses , a uniform nationwide informatics system , and the support of VHA administration and managerial staff BACKGROUND Disease registries , audit and feedback , and clinical reminders have been reported to improve care processes . OBJECTIVE To assess the effects of a registry-generated audit , feedback , and patient reminder intervention on diabetes care . DESIGN R and omized controlled trial conducted in a resident continuity clinic during the 2003–2004 academic year . PARTICIPANTS Seventy-eight categorical Internal Medicine residents caring for 483 diabetic patients participated . Residents r and omized to the intervention ( n = 39 ) received instruction on diabetes registry use ; quarterly performance audit , feedback , and written reports identifying patients needing care ; and had letters sent quarterly to patients needing hemoglobin A1c or cholesterol testing . Residents r and omized to the control group ( n = 39 ) received usual clinic education . MEASUREMENTS Hemoglobin A1c and lipid monitoring , and the achievement of intermediate clinical outcomes ( hemoglobin A1c < 7.0 % , LDL cholesterol < 100 mg/dL , and blood pressure < 130/85 mmHg ) were assessed . RESULTS Patients cared for by residents in the intervention group had higher adherence to guideline recommendations for hemoglobin A1c testing ( 61.5 % vs 48.1 % , p = .01 ) and LDL testing ( 75.8 % vs 64.1 % , p = .02 ) . Intermediate clinical outcomes were not different between groups . CONCLUSIONS Use of a registry-generated audit , feedback , and patient reminder intervention in a resident continuity clinic modestly improved diabetes care processes , but did not influence intermediate clinical outcomes Background : Thrombolytic treatment has been shown to be effective in the treatment of ischemic stroke when initiated within 3 hours of symptom onset , yet few patients receive thrombolytics . Objective : To estimate expected increases in use of thrombolytics for ischemic stroke given the following interventions : educating patients to present earlier , optimizing Emergency Medical Services ( EMS ) response/transport times , optimizing hospital systems , and extending the treatment window . Methods : As part of a Centers for Disease Control – sponsored Coverdell Acute Stroke Pilot Registry , the authors prospect ively identified all patients with an initial diagnosis of ischemic stroke at 11 hospitals in California over a 3-month period . Timing of symptom onset , EMS response , hospital arrival , treatment , and reasons for nontreatment were evaluated , and hypothetical treatment rates for thrombolysis for interventions on the stroke-care continuum were derived based on observed rates of eligibility and treatment . Results : Of 374 patients with ischemic stroke , 88 ( 23.5 % ) arrived at the emergency department within 3 hours of symptom onset , of whom 16 ( 4.3 % ) received thrombolysis . If all patients with known onset times had called 911 immediately , the expected overall rate of thrombolytic treatment within 3 hours would have increased from 4.3 to 28.6 % . Expected rates of thrombolysis were lower for other interventions : instantaneous prehospital response 5.5 % , perfect hospital care 11.5 % , and extension of time window to 6 hours 8.3 % . If all patients with known onset had arrived within 1 hour and been optimally treated , 57 % could have been treated . Conclusion : Campaigns that educate patients to seek treatment sooner should be major components of system-wide interventions to increase rates of thrombolysis for acute ischemic stroke BACKGROUND More information on the longitudinal care and outcomes of patients after myocardial infa rct ion ( MI ) is needed to further improve the quality of MI care . The PREMIER study was design ed to meet this need . METHODS Patients with MI were prospect ively screened and enrolled from 19 US centers between January 1 , 2003 , and June 28 , 2004 . Consenting patients had detailed chart abstract ions of their medical history and processes of inpatient care , supplemented with a detailed , patient-centered interview . Central ized follow-up at 1 , 6 , and 12 months is being conducted to quantify patients ' postdischarge care and outcomes , with a focus on their health status ( symptoms , function , and quality of life ) . In 2003 , detailed chart abstract ions , devoid of all personal health information , were collected for patients eligible but not enrolled in PREMIER . RESULTS Of 10,911 patients screened , 3953 were eligible and 2498 enrolled into PREMIER . Few clinical ly significant differences between the total MI population and those enrolled into PREMIER were observed . Adherence to accepted processes of quality care , such as aspirin and beta-blockers on admission ( 96 % and 91 % ) or discharge ( 96 % and 93 % ) , was high . One-month follow-up rates were high , with only 9 % of patients being lost to follow-up . CONCLUSION PREMIER is a novel registry with detailed insights into patients ' sociodemographic , clinical , and health status characteristics , as well as detailed monitoring of their inpatient and outpatient processes of care . Ultimately , PREMIER will describe patients ' health status outcomes and identify determinants of these outcomes as an important step toward improving MI care Background : End-of-life care for patients with advanced chronic kidney disease ( CKD ) is recognised as an important area for improvement . These patients have a significant mortality and , although some is unpredictable , there is a role for the nephrology multi-disciplinary team ( MDT ) and palliative care physicians to engage in advance care planning and support patients to discuss their preferences . Methods : Retrospective and prospect i ve data were obtained to conduct a comparison observational study to assess the impact of introducing a supportive care register on the end-of-life care for patients with advanced CKD . An electronic supportive care register was implemented . This required a programme of multi-disciplinary staff education , collaborative working with Palliative Care to establish renal-specific protocol s and dissemination activities . The impact of the intervention was assessed by analysing all deaths in two six-month periods where all those with an eGFR < 15 ml/min/1.73 m2 at the time of their death were included . Results : A total of 91 patients were included . Post-intervention , there was a 25.4 % ( 95 % CI : 6.5 - 44.3 % , p = 0.008 ) improvement in patients having a documented discussion about end-of-life planning . There was also a 19.7 % ( 95 % CI : 4.0 - 35.5 % , p = 0.01 ) improvement in establishing the place of death . All patients who expressed a preferred place of death died there . The intervention increased engagement with the wider MDT and led to significant improvements in access to specialist palliative care services . Conclusions : These results show that the interventions implemented to introduce a supportive care register result ed in meaningful improvements to the end-of-life care for patients in our region with advanced CKD Clinical registries play an important role in measuring healthcare delivery and supporting quality improvement for individuals with cardiovascular disease and stroke . Well- design ed clinical registry programs provide important mechanisms to monitor patterns of care , evaluate healthcare effectiveness and safety , and improve clinical outcomes . The use of clinical registries is likely to grow given the increasing focus on measuring and improving healthcare delivery and patient outcomes by stakeholders in both the private and public sectors . The American Heart Association ( AHA ) has a longst and ing commitment to promoting the innovative and effective use of clinical registries . The importance of clinical registries was highlighted recently in an AHA Scientific Statement on “ Essential Features of a Surveillance System to Support the Prevention and Management of Heart Disease and Stroke ” in the United States.1 This policy statement exp and s on the previous scientific statement by providing recommendations to policy makers and the healthcare community for expansion of the applications of existing and future clinical registries . The term “ clinical registry ” is defined here as an observational data base of a clinical condition , procedure , therapy , or population in which there are often no registry-m and ated approaches to therapy and relatively few inclusion or exclusion criteria . The focus of clinical registries is to capture data that reflect “ real-world ” clinical practice in large patient population s. The data from clinical registries do not replace the need for traditional r and omized controlled trials . Rather , registries and trials are complementary approaches , each with unique advantages and imperfections.2 Such clinical registries do not solely contain cl aims or administrative data yet may be linked to such data sources . There are at least 3 classifications of clinical registries based on the patient population , including procedure/therapy/encounter-based , disease-based , and population -based registries . Registries also can be classified from a functional perspective , such as whether the registry is used to conduct clinical research , BACKGROUND Disease registries are powerful tools with the potential to transform the way chronic diseases are managed . To date , however , little work has been done to determine how to optimize the implementation of a chronic disease registry in practice . METHODS Twenty-nine physicians and their nurse teams in a large community internal medicine practice participated in this 6-month prospect i ve r and omized trial in 2000 . Teams were assigned to one of three implementation strategies using information from a diabetes registry . Process and outcome measures for diabetes management were analyzed . Process measures included the percentage of patients completing glycosylated hemoglobin ( Hgb ) testing within 6 months and low-density lipoprotein ( LDL ) testing within 12 months . Outcome measures included the percentage of patients with a glycosylated Hgb > 9.3 % ( equivalent to a HgbA1c > 8.0 % ) , the percentage of patients with an LDL cholesterol > 130 mg/dl , and the percentage of patients with controlled blood pressure , defined as < 130/85 millimeters of mercury . Mean change in LDL and glycosylated Hgb values was also measured . RESULTS Teams r and omized to an intervention strategy that included direct letters to patients showed significant improvement across a number of measures . The improvement was most apparent among patients without recent testing or with poorly controlled disease . The two interventions that did not include direct patient letters result ed in limited improvement . DISCUSSION Disease registries can be used to improve outcomes in the management of diabetes and other chronic diseases . Better outcomes were seen in patients who received letters based on registry-generated data . This strategy should be included as part of a comprehensive chronic disease management plan . Further refinements in the use of registries should result in further incremental improvement Introduction Many developed countries have regional and national clinical registries aim ed at improving health outcomes of patients diagnosed with particular diseases or cared for in particular healthcare setting s. Clinical quality registries ( CQRs ) are clinical registries established with the purpose of monitoring quality of care and providing feedback to improve health outcomes . The aim of this systematic review is to underst and the impact of CQRs on ( 1 ) mortality/survival ; ( 2 ) measures of outcome that reflect a process or outcome of healthcare ; ( 3 ) healthcare utilisation and ( 4 ) costs . Methods and analysis The PRISMA -P methodology , checklist and st and ard strategy using predefined inclusion and exclusion criteria and structured data abstract ion tools will be followed . A search of the electronic data bases MEDLINE , EMBASE , Cochrane Central Register of Controlled Trials ( CENTRAL ) and CINAHL will be undertaken , in addition to Google Scholar and grey literature , to identify studies in English covering the period January 1980 to December 2014 . Case – control , cohort , r and omised controlled trials and controlled clinical trials which describe the registry as an intervention will be eligible for inclusion . Narrative synthesis of study findings will be conducted , guided by a conceptual framework developed to analyse the outcome measure of the registry using defined criteria . If sufficient studies are identified with a similar outcome of interest and measure using the same comparator and time of interval , results will be pooled for r and om-effects meta- analysis . Test for heterogeneity and sensitivity analysis will be conducted . To identify reporting bias , forest plots and funnel plots will be created and , if required , Egger 's test will be conducted . Ethics and dissemination Ethical approval is not required as primary data will not be collected . Review results will be published as a part of thesis , peer- review ed journal and conferences . Trial registration number CRD42015017319 CONTEXT Diabetes care is challenging in rural areas . Research has shown that the utilization of electronic patient registries improves care ; however , improvements generally have been described in combination with other ongoing interventions . The level of basic registry utilization sufficient for positive change is unknown . PURPOSE The goal of the current study was to examine differential effects of basic registry utilization on diabetes care processes and clinical outcomes according to level of registry use in a rural setting . METHODS Patients with diabetes ( N = 661 ) from 6 Federally Qualified Health Centers in rural West Virginia were entered into an electronic patient registry . Data from pre- and post-registry were compared among 3 treatment and control groups that had different levels of registry utilization : low , medium , or high ( for example , variations in the use of registry-generated progress notes examined at the point-of-care and in the accuracy of registry-generated summary reports to track patients ' care ) . Data included care processes ( annual exams , screens to promote wellness , education , and self-management goal - setting ) and clinical outcomes ( HbA1c , LDL , HDL , cholesterol , triglycerides , blood pressure ) . FINDINGS The registry assisted in significantly improving 12 of 13 care processes and 3 of 6 clinical outcomes ( HbA1c , LDL , cholesterol ) for patients exposed to at least medium levels of registry utilization , but not for the controls . For example , the percent of patients who had received an annual eye exam at follow-up was 11 % , 34 % , and 38 % for the low , medium , and high utilization groups , respectively ; only the latter groups improved . CONCLUSIONS As an initial step to achieving control of diabetes , basic registry utilization may be sufficient to drive improvements in provider-patient care processes and in patient outcomes in rural clinics with few re sources Background : Riks-Stroke , the Swedish national quality register on stroke care , provides unique opportunities to evaluate stroke units in routine clinical care . Methods : Basic patient characteristics , process indicators and outcome variables are recorded in all 85 hospitals admitting acute stroke patients . A 3-month follow-up is included . Results : There are wide variations between hospitals in the proportion of patients admitted to a stroke unit , in secondary prevention and in the proportion of patients in institutional care at 3 months . Even after adjustment for available prognostic indicators , case fatality is lower and functional outcome is better in patients treated in stroke units than in patients treated in general wards . Conclusion : Riks-Stroke shows that outcome is consistently better in patients treated in a stroke unit than in general wards , not only in r and omised trials but also in routine stroke care |
2,191 | 30,057,605 | These studies show that initially high vagal nerve activity predicts better cancer prognosis , and , in some studies , independent of confounders such as cancer stage and treatments .
The second part of this paper presents a comprehensive review including human and animal cohort and experimental studies showing that vagotomy accelerates tumor growth , while vagal nerve activation improves cancer prognosis .
Based on all review ed studies , it is concluded that the evidence supports a protective role of the vagus nerve in cancer and specifically in the metastatic stage | This article review s the role of the vagus nerve in tumor modulation and cancer prognosis .
Since the design of the epidemiological studies is correlational , any causal relationship between heart rate variability and cancer prognosis can not be inferred .
However , various semi-experimental cohort studies in humans and experimental studies in animals have examined this causal relationship . | Background A simple and accurate survival prediction tool can facilitate decision making processes for hospice patients with advanced cancers . The objectives of this study were to explore the association of cardiac autonomic functions and survival in patients with advanced cancer and to evaluate the prognostic value of heart rate variability ( HRV ) in 7-day survival prediction . Methods A prospect i ve study was conducted on 138 patients with advanced cancer recruited from the hospice ward of a regional hospital in southern Taiwan . Information on functional status and symptom burden of the patients was recorded . Frequency-domain HRV was obtained for the evaluation of cardiac autonomic functions at admission . The end point of the study was defined as the survival status at day 7 after admission to the hospice ward . Multivariate logistic regression analyses were performed to evaluate the independent associations between HRV indices and survival of 7 days or less . Results The median survival time of the patients was 20 days ( 95 % CI , 17–28 days ) . Results from the multivariate logistic regression analysis indicated that the natural logarithm-transformed high-frequency power ( lnHFP ) of a value less than 2 ( OR = 3.8 , p = 0.008 ) and ECOG performance status of 3 or 4 ( OR = 3.4 , p = 0.023 ) were significantly associated with a higher risk of survival of 7 days or less . Receiver operating characteristic ( ROC ) curve analysis revealed that the area under the curve was 0.71 ( 95 % CI , 0.61–0.81 ) . Conclusions In hospice patients with non-lung cancers , an lnHPF value below 2 at hospice admission was significantly associated with survival of 7 days or less . HRV might be used as a non-invasive and objective tool to facilitate medical decision making by improving the accuracy in survival prediction In patients with drug-resistant hypertension , chronic electric stimulation of the carotid baroreflex is an investigational therapy for blood pressure reduction . We hypothesized that changes in cardiac autonomic regulation can be demonstrated in response to chronic baroreceptor stimulation , and we analyzed the correlation with blood pressure changes . Twenty-one patients with drug-resistant hypertension were prospect ively included in a sub study of the Device Based Therapy in Hypertension Trial . Heart rate variability and heart rate turbulence were analyzed using 24-hour ECG . Recordings were obtained 1 month after device implantation with the stimulator off and after 3 months of chronic electric stimulation ( stimulator on ) . Chronic baroreceptor stimulation decreased office blood pressure from 185±31/109±24 mm Hg to 154±23/95±16 mm Hg ( P<0.0001/P=0.002 ) . Mean heart rate decreased from 81±11 to 76±10 beats per minute−1 ( P=0.001 ) . Heart rate variability frequency-domain parameters assessed using fast Fourier transformation ( FFT ; ratio of low frequency : high frequency : 2.78 versus 2.24 for off versus on ; P<0.001 ) were significantly changed during stimulation of the carotid baroreceptor , and heart rate turbulence onset was significantly decreased ( turbulence onset : −0.002 versus −0.015 for off versus on ; P=0.004 ) . In conclusion , chronic baroreceptor stimulation causes sustained changes in heart rate variability and heart rate turbulence that are consistent with inhibition of sympathetic activity and increase of parasympathetic activity in patients with drug-resistant systemic hypertension ; these changes correlate with blood pressure reduction . Whether the autonomic modulation has favorable cardiovascular effects beyond blood pressure control should be investigated in further studies BACKGROUND Patients with coronary heart disease ( CHD ) who experience depressed mood or psychological stress exhibit decreased vagal control of heart rate ( HR ) , as assessed by spectral analysis of HR variability ( HRV ) . Myocardial infa rct ion and sudden cardiac death are independently associated with depression and stress , as well as impaired vagal HR control . This study examined whether a behavioral neurocardiac intervention to reduce stress or depression can augment cardiovagal modulation in CHD patients . We hypothesized that ( 1 ) cognitive-behavioral training with HRV biofeedback would augment vagal recovery from acute stress , and ( 2 ) vagal regulation of HR would be inversely associated with stress and depression after treatment . METHODS This r and omized controlled trial enrolled 46 CHD patients from 3 clinics of CHD risk reduction in Toronto and Vancouver , Canada . Subjects were r and omized to five 1.5-hour sessions of HRV biofeedback or an active control condition . Outcome was assessed by absolute and normalized high-frequency spectral components ( 0.15 - 0.50 Hz ) of HRV , and by the Perceived Stress Scale and Centre for Epidemiologic Studies in Depression scale . RESULTS Both groups reduced symptoms on the Perceived Stress Scale ( P = .001 ) and Centre for Epidemiologic Studies in Depression scale ( P = .004 ) . Hierarchical linear regression determined that improved psychological adjustment was significantly associated with the high-frequency index of vagal HR modulation only in the HRV biofeedback group . Adjusted R 2 was as follows : HRV biofeedback group , 0.86 for stress ( P = .02 ) and 0.81 for depression ( P = .03 ) ; versus the active control group , 0.04 ( P = .57 ) and 0.13 ( P = .95 ) , respectively . CONCLUSION A novel behavioral neurocardiac intervention , HRV biofeedback , can augment vagal HR regulation while facilitating psychological adjustment to CHD Recent studies suggest that vagal nerve activity , indexed by heart rate variability ( HRV ) , could have a prognostic role in cancer . However , most studies did not control adequately for confounders and included cardiac patients . Furthermore , the validity of this prognostic role needs to be tested in different types of cancer . The present study tested the prognostic role of HRV in prostate cancer ( PC ) and non-small cell lung cancer ( NSCLC ) patients , using a historical prospect i ve design . HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients . Outcomes included prostate-specific antigen ( PSA ) at 6 and 24 months in PC , and overall survival ( OS ) ( for the full sample ) and survival time ( for the deceased patients ) in NSCLC . Furthermore , the possible mediating role of C-reactive protein ( CRP ) was tested ( in NSCLC ) , as well as whether age and stage moderated the relationship between HRV and prognosis in both types of cancer . In the PC patients , HRV significantly inversely predicted PSA levels at 6 and 24 months , independent of confounders . Furthermore , this was particularly significant in metastatic PC patients , indicating moderation by stage . In NSCLC patients , HRV did not predict OS and survival time , but it did positively predict survival time in patients under the age of 65 , independent of confounders . Additionally , CRP was not found to mediate the relationship between HRV and OS or survival time in NSCLC . The present results partly support previous studies and extend them to two additional common types of cancer , using a more rigorous control over confounders . Together with recent experimental findings , these results propose a modulatory role of vagal nerve activity in cancer . Therefore , routine measurement of HRV in estimating prognosis in cancer may be considered In a historical prospect i ve cohort investigation of 4131 patients undergoing peptic ulcer surgery in 53 hospitals in the western part of Denmark from 1955 through 1960 , the risk of subsequent gastric cancer development was studied . The patients were followed with regard to gastric cancer development until their death or the end of the year 1982 and the incidence of cancer in this cohort was compared to the incidence in the total population in the same region during the same period . A total of 46 gastric cancers were diagnosed versus 47 expected . Up to 15 years after operation the cancer risk was lower than expected . After 15 years the risk was higher than expected with a 2.1-fold higher incidence after 25 years for the total patient population . The highest risk was observed in male subjects undergoing a Billroth II subtotal gastrectomy with a 3.2 times increase in risk after 25 years . There was no difference between gastric and duodenal ulcer patients ; and patients undergoing simple suture for a perforated ulcer showed no increase in cancer incidence . Patients with long-lasting symptoms had the same incidence as patients with briefer symptoms . These observations indicate that the operation per se and not the ulcer disease may be precancerous The present study was design ed to examine the effect of heart rate variability ( HRV ) biofeedback on the cardiorespiratory resting function during sleep in daily life . Forty-five healthy young adults were r and omly assigned to one of three groups : HRV biofeedback , Autogenic Training ( AT ) , and no-treatment control . Participants in the HRV biofeedback were instructed to use a h and held HRV biofeedback device before their habitual bedtime , those in the AT were asked to listen to an audiotaped instruction before bedtime , and those in the control were asked to engage in their habitual activity before bedtime . Pulse wave signal during sleep at their own residences was measured continuously with a wristwatch-type transdermal photoelectric sensor for three time points . Baseline data were collected on the first night of measurements , followed by two successive nights for HRV biofeedback , AT , or control . Cardiorespiratory resting function was assessed quantitatively as the amplitude of high-frequency ( HF ) component of pulse rate variability , a surrogate measure of respiratory sinus arrhythmia . HF component increased during sleep in the HRV biofeedback group , although it remained unchanged in the AT and control groups . These results suggest that HRV biofeedback before sleep may improve cardiorespiratory resting function during sleep OBJECTIVES The purpose of this study was to test the transcutaneous noninvasive vagus nerve stimulator ( nVNS ) ( gammaCore © ) device to determine if it modulates the peripheral immune system , as has been previously published for implanted vagus nerve stimulators . MATERIAL S AND METHODS A total of 20 healthy males and females were r and omized to receive either nVNS or sham stimulation ( SST ) . All subjects underwent an initial blood draw at 8:00 am , followed by stimulation with nVNS or SST at 8:30 am . Stimulation was repeated at 12:00 pm and 6:00 pm . Additional blood sample s were withdrawn 90 min and 24 hour after the first stimulation session . After sample s were cultured using the Myriad RBM TruCulture ( Austin , TX ) system ( WBCx ) , levels of cytokines and chemokines were measured by the Luminex assay and statistical analyses within and between groups were performed using the Wilcoxon Signed Ranks Test and Mann-Whitney U with the statistical program R. RESULTS A significant percent decrease in the levels of the cytokine interleukin [IL]-1β , tumor necrosis factor [ TNF ] levels , and chemokine , interleukin [IL]-8 IL-8 , macrophage inflammatory protein [MIP]-1α , and monocyte chemoattractant protein [MCP]-1 levels was observed in the nVNS group non-lipopolysaccharide (LPS)-stimulated whole blood culture ( n-WBCx ) at the 24-hour time point ( p < 0.05 ) . In SST group , there was a significant percent increase in IL-8 at 90 min post-stimulation ( p < 0.05 ) . At 90 min , the nVNS group had a greater percent decrease in IL-8 concentration ( p < 0.05 ) compared to SST group . The nVNS group had a greater percent decrease in cytokines ( TNF , IL-1β ) and chemokines ( MCP-1 and IL-8 ) at 24 hour ( p < 0.05 ) in comparison to SST . LPS-stimulated whole blood cultures ( L-WBCx ) did not show a significant decrease in cytokine levels in either the nVNS or SST group across any time points . The nVNS group showed a significant percent increase in LPS-stimulated IL-10 levels at the 24-hour time point in comparison to SST . CONCLUSIONS nVNS downregulates inflammatory cytokine release suggesting that nVNS may be an effective anti-inflammatory treatment Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes . Recently , a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed . In healthy subjects , a prominent fMRI BOLD signal deactivation in the limbic system was found . The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time . A total of 37 patients suffering from major depression were included in two r and omized sham controlled add-on studies . Patients were stimulated five times a week on a daily basis for the duration of 2 weeks . On days 0 and 14 , the Hamilton Depression Rating Scale ( HAMD ) and the Beck Depression Inventory ( BDI ) were assessed . In contrast to sham-treated patients , electrically stimulated persons showed a significantly better outcome in the BDI . Mean decrease in the active treatment group was 12.6 ( SD 6.0 ) points compared to 4.4 ( SD 9.9 ) points in the sham group . HAMD score did not change significantly in the two groups . An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown for the first time in this controlled pilot study . Regarding the limitations of psychometric testing , the risk of unblinding for technical reasons , and the small sample size , further studies are necessary to confirm the present results and verify the practicability of tVNS in clinical fields CONTEXT A better time-to-death ( TTD ) prediction can facilitate decision-making processes related to plans for providing effective end-of-life care for patients in hospice wards . OBJECTIVE To explore the association of cardiovascular autonomic functions with TTD in patients with terminal hepatocellular carcinoma . METHODS A prospect i ve study was conducted with 33 patients with hepatocellular carcinoma recruited from the hospice ward of a regional hospital in Chiayi county , Taiwan . Serum creatinine , serum glutamate oxaloacetate transaminase , serum glutamate pyruvate transaminase , blood urea nitrogen ( BUN ) , and serum albumin were measured on the admission day . Cardiovascular autonomic functions were evaluated by frequency-domain measures of heart rate variability ( HRV ) on admission . RESULTS TTD was significantly associated with total spectrum power ( TP ) ( r=0.55 , P=0.001 ) and high frequency ( HF power ) ( r=0.44 , P=0.010 ) of HRV measurement . The accuracy of within-one-week TTD prediction was 67 % for TP and HF power . The accuracy of within-two-week TTD prediction was 82 % for TP and 73 % for HF . In addition , TTD of the patients was also significantly associated with serum creatinine ( r=-0.42 , P=0.015 ) , serum albumin ( r=-0.46 , P=0.007 ) , and BUN ( r=-0.44 , P=0.010 ) . CONCLUSION This is the first study to evaluate the association between cardiovascular autonomic functions and TTD in patients with terminal hepatocellular carcinoma . The inclusion of HRV measurement in prognostic models may improve accuracy in TTD prediction and , hence , facilitate medical decision making in hospice care The parasympathetic system , and primarily the vagus nerve , informs the brain about multiple signals and returns the body to homeostasis . Recent studies have shown that vagal nerve activity independently predicts prognosis in cancer . Here , we take this one step further and show that when vagal nerve activity is high , cancer stage no longer predicts tumor burden . We examined whether vagal nerve activity , indexed by Heart Rate Variability ( HRV ) , moderated the effects of initial tumor stage on tumor burden at followup . Patients ' HRVs were derived from ECGs near diagnosis in colorectal cancer ( CRC ) and in prostate cancer ( PC ) patients . Outcomes included the tumor markers carcinoembryonic antigen ( CEA ) at 12 months for CRC and prostate-specific antigen ( PSA ) at 6 months for PC . As would be expected , initially advanced tumor stages of CRC or PC predicted higher tumor marker levels at follow-up than did early stages . However , this occurred only in patients with low , not high , vagal activity ( HRV ) . Furthermore , in patients with advanced tumor stage at diagnosis , high HRV predicted lower tumor marker levels than did low HRV , in both cancers . Estimating a cancer patient 's prognosis by determining his tumor stage needs to also consider the vagal nerve activity . This activity is easily measurable , and it determines in which subjects the tumor stage is prognostic . Importantly , higher vagal activity may even protect against the adverse effects of advanced cancer stage . These findings , observed in two distinct cancers , support the hypothesized neuroimmunomodulatory effects of vagal nerve activity on tumors CONTEXT Autonomic nervous system dysfunction ( AD ) is a common syndrome in patients with advanced cancer . It is associated with decreased survival in several patient population s , including diabetes mellitus , heart failure , and neurological diseases . Based on this evidence , we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer . OBJECTIVES The objective of this preliminary study was to test the association between AD , as measured by the st and ardized Ewing test and heart rate variability ( HRV ) measures , and survival in this patient population . METHODS We examined the relationship between survival and parameters of AD in subjects who participated in a prospect i ve study of autonomic dysfunction and hypogonadism in male patients with advanced cancer . Eligibility criteria were defined based on the prospect i ve study protocol . We collected demographic information , date of death ( obtained from the online Social Security Death Index data base ) , date of study entry , and Ewing and HRV scores . We defined survival as the interval between study entry and date of death . A survival analysis was used to test the association between survival ( in days ) and Ewing test ( 0 - 5 ) and measures of HRV , including time domain ( st and ard deviation of normal to normal beat interval [ SDNN ] ) and frequency domain ( ultra low , very low , low , and high ) . Four patients were still alive at the time of this study and included in the survival analysis as being censored . RESULTS Forty-seven male patients were included in this study . Median age was 59 years ( range : 20 - 79 ) , and 30 out of 47 ( 63 % ) were Caucasians . AD , defined as Ewing score greater than 2 , was present in 38 out of 47 ( 80 % ) of the patients . Median Ewing score was 3 ( 1 - 5 ) , indicating moderate to severe AD . Spearman correlation for Ewing score and SDNN was 0.44 ( P = 0.002 ) . There was a significant association between abnormal Ewing score and survival ( P < 0.0001 ) and abnormal SDNN HRV and survival ( P = 0.056 ) . CONCLUSION AD is associated with shorter survival in male patients with advanced cancer . Further longitudinal research in a large cohort is justified based on CNI-1493 , an inhibitor of proinflammatory cytokines , was studied in a Phase I trial in melanoma and renal cancer patients receiving high-dose interleukin 2 ( IL-2 ) . Objectives of the study were to define the maximum tolerated dose ( MTD ) and toxicity of CNI-1493 , to assess its pharmacological effects , and to define its pharmacokinetics . Twenty-four patients were treated in sequential cohorts with CNI-1493 doses from 2 through 32 mg/m2 daily . Patients first received only CNI-1493 daily for 5 days . After a 9-day rest , patients received two 5-day courses of IL-2 of 600,000 IU/kg every 8 h for up to 14 doses/course plus daily CNI-1493 ; courses were separated by a 9-day rest period . CNI-1493 administered alone was well tolerated at doses through 32 mg/m2 ; MTD was not reached . The only clinical toxicity attributed to CNI-1493 was occasional injection-site phlebitis . Grade 1 creatinine increases occurred in 1 of 7 patients at 4 mg/m2 , in 1 of 1 patients at 25 mg/m2 , and in 3 of 6 patients at 32 mg/m2 CNI-1493 alone . In combination with high-dose IL-2 , CNI-1493 at > or = 25 mg/m2 seemed to exacerbate IL-2-induced nephrotoxicity : grade 3 or 4 creatinine increases developed in 3 of 6 patients at 25 or 32 mg/m2 , as compared with 1 of 16 patients at doses < or = 16 mg/m2 . The MTD for CNI-1493 given with high-dose IL-2 was 16 mg/m2 . The dose-limiting toxicity of IL-2 was hypotension in 63 % of patients ; overall tolerance to IL-2 was not improved by CNI-1493 . However , relative to changes seen in a reference group receiving high-dose IL-2 alone , at doses > or = 4 mg/m2 CNI-1493 did show evidence of pharmacological activity as an inhibitor of tumor necrosis factor production BACKGROUND Identifying new prognostic factors is important for guiding treatments and preventing metastasis in cancer . Vagal nerve activity may predict prognosis in cancer due to its roles in modulating inflammation , sympathetic activity and oxidative stress . This study tested the relationship between heart rate variability ( HRV ) , a vagal nerve index , and the colon cancer ( CC ) marker carcinoembryonic antigen ( CEA ) , in an ' historical prospect i ve ' design . METHODS We examined data of 72 CC patients , without inflammatory or cardiac diseases , of whom 38 had baseline electrocardiograms ( ECG ) and 12 month CEA levels . We measured HRV ( SDNN , RMSSD ) from brief archived ECG . Multiple confounders were considered . RESULTS Controlling for effects of tumor stage and treatment-orientation , baseline HRV predicted CEA levels at 12 months ( r=-.43 , p=.006 ) . Patients with SDNN<20 ms had significantly higher CEA at 12months than those with SDNN>20 ms . CONCLUSION These preliminary results showed that higher HRV predicts lower levels of a tumor marker , one year later , independent of confounders . This supports the hypothesized role of vagal activity in tumor modulation . Replication in larger sample s is needed Background / Aims : Recently , a decrease in heart rate variability measures was found in patients with carcinoid syndrome suffering from carcinoid heart disease compared to those without cardiac involvement of carcinoid syndrome . The prognostic relevance of this finding , however , was not clear . Patients and Methods : Therefore , 35 patients with carcinoid syndrome ( 21 men , age 56 ± 11 years ) , all of them suffering from metastatic carcinoid tumors , were followed prospect ively at our institution . Digital 24-hour Holter monitoring , echocardiography , and serum serotonin and urine 5-hydroxyindole acetic acid ( 5-HIAA ) samplings were performed in all study patients at baseline . Indices of time domain heart rate variability obtained from Holter recordings included the st and ard deviation of all normal RR intervals ( SDNN ) representing overall variability , the square root of the mean of the squared differences between adjacent normal RR intervals ( rMSSD ) , and the percentage of the number of pairs of adjacent normal RR intervals differing by > 50 ms ( pNN50 ) , both indices reflecting predominantly vagal influences on heart rate . Results : During a mean follow-up of 18 ± 7 months , 15 of 35 patients with carcinoid syndrome ( 43 % ) died . Patients with cardiac manifestation of the carcinoid syndrome showed a tendency towards an increased mortality in comparison to patients without cardiac involvement ( p = 0.09 ) . Patients with the combination of decreased heart rate variability ( SDNN < 100 ms ) and presence of carcinoid heart disease had a significant worse prognosis ( p = 0.04 ) compared to patients without carcinoid heart disease and preserved heart rate variability ( SDNN ≧100 ms ) . Conclusions : The presence of carcinoid heart disease in combination with decreased heart rate variability is associated with the most adverse prognosis in the setting of carcinoid syndrome |
2,192 | 30,371,961 | Taking into account the long-term follow-up of cohort studies , estimation of HRs for time-dependent events like T2DM incidence appeared most reliable .
Overall prognosis of people with IH worsened over time .
T2DM cumulative incidence generally increased over the course of follow-up but varied with IH definition .
Regression from IH to normoglycaemia decreased over time but was observed even after 11 years of follow-up .
The risk of developing T2DM when comparing IH with normoglycaemia at baseline varied by IH definition . | BACKGROUND Intermediate hyperglycaemia ( IH ) is characterised by one or more measurements of elevated blood glucose concentrations , such as impaired fasting glucose ( IFG ) , impaired glucose tolerance ( IGT ) and elevated glycosylated haemoglobin A1c ( HbA1c ) .
These levels are higher than normal but below the diagnostic threshold for type 2 diabetes mellitus ( T2DM ) .
The reduced threshold of 5.6 mmol/L ( 100 mg/dL ) fasting plasma glucose ( FPG ) for defining IFG , introduced by the American Diabetes Association ( ADA ) in 2003 , substantially increased the prevalence of IFG .
Likewise , the lowering of the HbA1c threshold from 6.0 % to 5.7 % by the ADA in 2010 could potentially have significant medical , public health and socioeconomic impacts .
OBJECTIVES To assess the overall prognosis of people with IH for developing T2DM , regression from IH to normoglycaemia and the difference in T2DM incidence in people with IH versus people with normoglycaemia . | Background A simple diabetes risk tool that does not require laboratory tests would be beneficial in screening individuals at higher risk . Few studies have evaluated the ability of these tools to identify new cases of pre-diabetes . This study aim ed to assess the ability of the American Diabetes Association Risk Tool ( ADART ) to predict the 3-year incidence of pre-diabetes and diabetes in Taiwanese . Methods This was a 3-year prospect i ve study of 1021 residents with normoglycemia at baseline , gathered from a r and om sample of residents aged 40–88 years in a metropolitan city in Taiwan . The areas under the curve ( AUCs ) of three models were compared : ADART only , ADART plus lifestyle behaviors at baseline , and ADART plus lifestyle behaviors and biomarkers at baseline . The performance of ADART was compared with that of 16 tools that had been reported in the literature . Results The AUCs and their 95 % confidence intervals ( CIs ) were 0.60 ( 0.54–0.66 ) for men and 0.72 ( 0.66–0.77 ) for women in model 1 ; 0.62 ( 0.56–0.68 ) for men and 0.74 ( 0.68–0.80 ) for women in model 2 ; and 0.64 ( 0.58–0.71 ) for men and 0.75 ( 0.69–0.80 ) for women in model 3 . The AUCs of these three models were all above 0.7 in women , but not in men . No significant difference in either women or men ( p = 0.268 and 0.156 , respectively ) was observed in the AUC of these three models . Compared to 16 tools published in the literature , ADART had the second largest AUC in both men and women . Conclusions ADART is a good screening tool for predicting the three-year incidence of pre-diabetes and diabetes in females of a Taiwanese population . The performance of ADART in men was similar to the results with other tools published in the literature . Its performance was one of the best among the tools reported in the literature BACKGROUND The aim of this study was to develop a risk score to predict the 4-year risk of diabetes in a middle-aged Korean cohort . METHODS AND RESULTS Participants without diabetes ( 6,342 participants , aged 40 - 69 years ) were included and biennial follow ups were conducted . A logistic regression analysis was used to construct the models . The basic model was based on simple information such as age , parental or sibling history of diabetes , smoking status , body mass index , and hypertension , while clinical model 1 was constructed by adding biochemical tests such as fasting plasma glucose , high-density lipoprotein-cholesterol and triglycerides to the basic model ; clinical model 2 further added glycated hemoglobin ( HbA(1c ) ) to clinical model 1 . The model accuracy was assessed using area under a receiver operating characteristic ( AROC ) curve and the Hosmer-Lemeshow statistics . Both net reclassification improvement ( NRI ) and integrated discrimination improvement ( IDI ) were calculated to determine the contribution of HbA(1c ) . Two clinical models improved model discrimination ( AROC=0.75 and 0.77 ) when compared with the basic model ( AROC=0.65 ) . The addition of HbA(1c ) to clinical model 1 increased AROC by only 0.02 despite its high impact on the prediction of diabetes ( odds ratio=2.66 ) . However , the NRI and IDI were significantly improved with the addition of HbA(1c ) Therefore , a risk score system was developed to estimate the 4-year risk of diabetes based on clinical model 2 . CONCLUSIONS A risk score derived from simple biochemical examinations including HbA(1c ) can help identify those at a high risk of diabetes in a middle-aged Korean cohort OBJECTIVE To create a simple prediction rule that could perform as well as the 2-h postchallenge plasma glucose ( PCPG ) test to predict those at risk for diabetes . We created a prediction rule in one sample and prospect ively vali date d it for incident diabetes in a separate cohort . RESEARCH DESIGN AND METHODS A cross-sectional analysis with data from the Rancho Bernardo Study ( age 67 + /- 11 years ) to derive a rule predicting abnormal PCPG > /=140 mg/dl , using demographic , clinical , and laboratory data of nondiabetic participants with fasting plasma glucose ( FPG ) < 126 mg/dl . Data from the Health , Aging and Body Composition study ( age 74 + /- 3 years ) were used to prospect ively vali date this rule for incident diabetes and compare it with the predictive ability of the PCPG test . RESULTS Of 1,549 RBS participants , 514 ( 33 % ) had PCPG > /=140 mg/dl . Female sex , age , triglycerides , and FPG were most significantly associated with abnormal PCPG . Based on st and ardized beta-coefficients , we allotted 1 point for female sex , triglycerides > /=150 mg/dl , or FPG 95 - 104 mg/dl . Age > /=70 years or FPG 105 - 115 mg/dl were given 2 points , and FPG 116 - 125 mg/dl received 3 points . In the validation cohort , this simple prediction rule was as good as the 2-h PCPG test for predicting incident diabetes ( C-statistic : 0.71 for both ) . CONCLUSIONS Advanced age , female sex , FPG , and triglycerides were able to predict adults at risk for diabetes equally well as the 2-h PCPG test . Using this rule , clinicians may better identify older persons who should receive intensive lifestyle intervention to prevent type 2 diabetes OBJECTIVE Hemoglobin A1c ( HbA1c ) can be used to assess type 2 diabetes ( T2D ) risk . We asked whether HbA1c was associated with T2D risk in four scenarios of clinical information availability : 1 ) HbA1c alone , 2 ) fasting laboratory tests , 3 ) clinic data , and 4 ) fasting laboratory tests and clinic data . RESEARCH DESIGN AND METHODS We studied a prospect i ve cohort of white ( N = 11,244 ) and black ( N = 2,294 ) middle-aged participants without diabetes in the Framingham Heart Study and Atherosclerosis Risk in Communities study . Association of HbA1c with incident T2D ( defined by medication use or fasting glucose [ FG ] ≥126 mg/dL ) was evaluated in regression models adjusted for 1 ) age and sex ( demographics ) ; 2 ) demographics , FG , HDL , and triglycerides ; 3 ) demographics , BMI , blood pressure , and T2D family history ; or 4 ) all preceding covariates . We combined results from cohort and race analyses by r and om-effects meta-analyses . Subsidiary analyses tested the association of HbA1c with developing T2D within 8 years or only after 8 years . RESULTS Over 20 years , 3,315 individuals developed T2D . With adjustment for demographics , the odds of T2D increased fourfold for each percentage-unit increase in HbA1c . The odds ratio ( OR ) was 4.00 ( 95 % CI 3.14 , 5.10 ) for blacks and 4.73 ( 3.10 , 7.21 ) for whites , result ing in a combined OR of 4.50 ( 3.35 , 6.03 ) . After adjustment for fasting laboratory tests and clinic data , the combined OR was 2.68 ( 2.15 , 3.34 ) over 20 years , 5.79 ( 2.51 , 13.36 ) within 8 years , and 2.23 ( 1.94 , 2.57 ) after 8 years . CONCLUSIONS HbA1c predicts T2D in different common scenarios and is useful for identifying individuals with elevated T2D risk in both the short- and long-term OBJECTIVE To evaluate the incidence and relative risk of type 2 diabetes defined by the newly proposed HbA1c diagnostic criteria in groups categorized by different baseline HbA1c levels . RESEARCH DESIGN AND METHODS Using data from the European Prospect i ve Investigation of Cancer (EPIC)-Norfolk cohort with repeat HbA1c measurements , we estimated the prevalence of known and previously undiagnosed diabetes at baseline ( baseline HbA1c ≥6.5 % ) and the incidence of diabetes over 3 years . We also examined the incidence and corresponding odds ratios ( ORs ) by different levels of baseline HbA1c . Incident diabetes was defined clinical ly ( self-report at follow-up , prescribed diabetes medication , or inclusion on a diabetes register ) or biochemically ( HbA1c ≥6.5 % at the second health assessment ) , or both . RESULTS The overall prevalence of diabetes was 4.7 % ; 41 % of prevalent cases were previously undiagnosed . Among 5,735 participants without diabetes at baseline ( identified clinical ly or using HbA1c criteria , or both ) , 72 developed diabetes over 3 years ( 1.3 % [ 95 % CI 1.0–1.5 ] ) , of which 49 % were identified using the HbA1c criteria . In 6 % of the total population , the baseline HbA1c was 6.0–6.4 % ; 36 % of incident cases arose in this group . The incidence of diabetes in this group was 15 times higher than in those with a baseline HbA1c of < 5.0 % ( OR 15.5 [ 95 % CI 7.2–33.3 ] ) . CONCLUSIONS The cumulative incidence of diabetes defined using a newly proposed HbA1c threshold in this middle-aged British cohort was 1.3 % over 3 years . Targeting interventions to individuals with an HbA1c of 6.0–6.4 % might represent a feasible preventive strategy , although complementary population -based preventive strategies are also needed to reduce the growing burden of diabetes Aims In a population at risk for type 2 diabetes ( T2DM ) , we assessed early physical and metabolic markers that predict progression from normal to impaired glucose tolerance ( IGT ) and T2DM . Methods A total of 388 individuals ( 22 % male , age 46 + 11 years ) at risk for T2DM were r and omized to St and ard ( n = 182 ) or Intervention ( n = 206 ) care and evaluated at baseline and 5 annual follow-up visits , including blood pressure , BMI , A1C , lipids , urine albumin/creatinine ratio , VO2max , fasting glucose , insulin and C-peptide . The St and ard group received results of annual lab tests and quarterly newsletters , while the Intervention group received quarterly newsletters and detailed discussion s of lab results , routine self-directed activities , semi-annual group meetings and monthly telephone calls for ongoing support . Results Overall , 359 ( 93 % ) returned for at least one follow-up visit and 272 ( 70 % ) completed the final 5-year assessment . Return rates , changes in measures and incidence of IGT/T2DM were similar between groups . Low cardiorespiratory fitness ( VO2max ) was the most prevalent baseline abnormality . A1C and BMI were significant predictors of IGT/T2DM after controlling for other factors . The risk of IGT/T2DM within 5 years was 17.16 ( 95 % CL : 6.169 , 47.736 ) times greater for those with baseline A1C>=5.8 % as compared to those < 5.8 % ( p < 0.0001 ) . Conclusion Baseline A1C>=5.8 % was a significant predictor of IGT/T2DM within 5 years in a population at high risk for T2DM . A1C is routinely performed among patients with diabetes , however these data and other evidence suggest that it may also be a useful tool for risk assessment and screening OBJECTIVE Although an excess transmission of type 2 diabetes from mothers has been documented , whether this is an independent trait or whether the effect can be detected early through risk factors for type 2 diabetes remains to be eluci date d. The objective of this study was to investigate the prevalence of and the possible prospect i ve effect of family history on type 2 diabetes incidence adjusted for multiple diabetes risk factors in a 22.5-year follow-up study of healthy men . RESEARCH DESIGN AND METHODS A total of 1,947 apparently healthy nondiabetic men with fasting blood glucose ( FBG ) levels < 110 mg/dl at baseline , in whom an intravenous glucose tolerance test ( IVGTT ) was administered and several conventional risk factors were measured , were followed for 22.5 years . Family history data were obtained at the baseline examination , and morbidity data were obtained from repeated investigations , hospital records , and death certificates . RESULTS A total of 131 men reported maternal diabetes family history only , 65 men reported paternal diabetes family history only and 10 men reported both maternal and paternal diabetes family history . Among the 1,947 men , 143 cases of type 2 diabetes developed during 22.5 years of observation . Maternal family history and combined maternal and paternal family history predisposed to future type 2 diabetes both in univariate Cox analysis and in multivariate Cox regression analysis after adjusting for glucose disappearance rate ( Rd ) during an IVGTT , FBG level , BMI , physical fitness , triglyceride level , and age . Maternal family history showed a relative risk ( RR ) of 2.51 ( 95 % CI 1.55 - 4.07 ) , combined maternal and paternal family history showed an RR of 3.96 ( 1.22 - 12.9 ) , and paternal family history showed an RR of 1.41 ( 0.657 - 3.05 ) in multivariate analysis . CONCLUSIONS Maternal family history appears to be an important risk factor for type 2 diabetes independent of prediabetic Rd , FBG , BMI , and physical fitness levels Summary A longitudinal study of 266 r and omly selected non-diabetic Nauruans ( 215 normal subjects , 51 with impaired glucose tolerance ) has permitted the natural history of impaired glucose tolerance to be studied in this Micronesian population . Nauruans are known to suffer from a very high prevalence of abnormal glucose tolerance . The subjects were first examined in 1975–1976 , and a follow-up examination was performed in 1982 . Of the subjects with impaired glucose tolerance , 26 % developed diabetes during the study period ( 4 % per annum ) compared with 7 % of normal subjects ( 1 % per annum ) . After controlling for the effects of both age and obesity , the risk of subsequent diabetes for subjects with impaired glucose tolerance remained significantly higher than for normal subjects ( odds ratio 3.6 , 95 % confidence interval 1.4–9.1 ) . Of those with impaired glucose tolerance on initial examination , 39 % were normoglycaemic at follow-up . In subjects with impaired glucose tolerance , of nine factors examined only plasma glucose concentration at the time of the initial examination was consistent in predicting progression to diabetes , when the data were examined by both univariate and multivariate methods . Both 2-h and fasting plasma glucose values were useful predictors . Thus , Nauruans with impaired glucose tolerance have a higher risk of subsequent diabetes than their normoglycaemic counterparts , after controlling for age and obesity . Nevertheless , the prognosis of impaired glucose tolerance is unpredictable as a substantial proportion of such subjects return to normality . Plasma glucose concentration is the most important predictor of subsequent diabetes . These results accord with recent findings from longitudinal studies of impaired glucose tolerance in other population Obesity rates in Cyprus are very high and epidemiological information on type 2 diabetes mellitus is limited . The correlates of type 2 diabetes among adults remain unknown in the Cypriot population . Thus , the purpose of this study is to provide the first national estimate of the prevalence of type 2 diabetes and investigate its correlates . A r and omly stratified nationally sample of 1001 adults aged 18 - 80 participated in the study . Only 950 subjects completed the study . All subjects were free of any diseases ( known diabetes , kidney , liver ) , medication and supplementation . The overall prevalence of diabetes and pre-diabetes based on WHO criteria was 9.2 % and 16.3 % , respectively . After adjusting for age , energy intake , smoking and physical activity participants with obesity ( BMI ) ( OR=2.00 , P<0.001 ) , waist circumference ( WC ) ( OR=2.08 , P<0.001 ) , hypertension ( HT ) ( OR=1.99 , P<0.001 ) and hypercholesterolemia ( HC ) ( OR=2.07 , P<0.007 ) were most likely to develop T2DM compared with the normal ones . The odds of having diabetes were also found significant between subjects with high levels of triglycerides ( TG ) ( OR=1.49 , P<0.007 ) , compared with the normal ones and between subjects with low levels of HDL ( OR=1.44 , P<0.008 ) compared with the ones with high levels of HDL . The prevalence of type 2 diabetes in Cyprus is relatively medium-high . However , the pre-diabetes rates are very high showing a promising increase toward total rates of type 2 diabetes . Obesity , HT , WC , TG , HC and low HDL are all strong correlates of type 2 diabetes . Healthy education programs should be initiated for young and older-aged people and those with described abnormal risk factors AIM The aim of this study was to evaluate and quantify the role of different risk factors in the long-term development of Type 2 diabetes mellitus in a rural Italian population . METHODS The Brisighella Heart Study ( BHS ; 1972 - 2003 ) is a prospect i ve , population -based longitudinal epidemiological cohort involving 2939 r and omly selected subjects , aged 14 - 84 years , resident in the rural Italian town of Brisighella . For this study , we r and omly selected 1441 adult subjects representative of the Brisighella population ; consecutively visited during three BHS surveys . A step-wise Cox regression analysis determined the prognostic significance of each independent risk factor for the development of Type 2 diabetes in the 8-year long follow-up . RESULTS Blood pressure , high-density lipoprotein cholesterol , triglycerides , physical activity , total energy intake , and drug treatment had no effect on the incidence of diabetes . Age was a significant predictor of Type 2 diabetes when inserted alone in the model ( P = 0.007 ) , but irrelevant when adjusted for baseline body mass index ( BMI ) and or fasting plasma glucose . Among these with impaired fasting glucose ( IFG ) , the diabetes incidence/year was estimated to be 6.6 % for men and 11.2 % for women ( P < 0.001 ) . Basal glycaemia under 6.1 mmol/l were not significant long-term predictors of diabetes development , while higher basal glycaemia and each level BMI were . CONCLUSION Our findings confirm that IFG and BMI predict Type 2 diabetes development in our population . This should help to identify effective approaches to prevention Summary The aims of the present study were to observe the natural history of impaired glucose tolerance and to identify predictors for development of non-insulin-dependent diabetes mellitus ( NIDDM ) . A survey of glucose tolerance was conducted in subjects aged 50–74 years , r and omly selected from the registry of the middle-sized town of Hoorn in the Netherl and s. Based on the mean values of two oral glucose tolerance tests subjects were classified in categories of glucose tolerance according to the World Health Organization criteria . All subjects with impaired glucose tolerance ( n=224 ) were invited to participate in the present study , in which 70 % ( n=158 ) were subsequently enrolled . During follow-up subjects underwent a repeated paired oral glucose tolerance test . The mean follow-up time was 24 months ( range 12–36 months ) . The cumulative incidence of NIDDM was 28.5 % ( 95 % confidence interval 15–42 % ) . Age , sex , and anthropometric and metabolic characteristics at baseline were analysed simultaneously as potential predictors of conversion to NIDDM using multiple logistic regression . The initial 2-h post-load plasma glucose levels and the fasting proinsulin levels were significantly ( p<0.05 ) related to the incidence of NIDDM . Anthropometric characteristics , the 2-h post-load specific insulin levels and the fasting proinsulin/fasting insulin ratio were not related to the incidence of NIDDM . These results suggest that beta-cell dysfunction rather than insulin resistance plays the most important role in the future development of diabetes in a high-risk Caucasian population OBJECTIVE We studied the relationship between liver enzymes and the development of diabetes in a general Japanese population . RESEARCH METHODS AND PROCEDURES A total of 1804 non-diabetic subjects 40 to 79 years of age were followed-up prospect ively for a mean of 9.0 years . RESULTS During the follow-up , 135 subjects developed diabetes . In both sexes , the age-adjusted cumulative incidence of diabetes increased significantly with elevating quartiles of serum gamma-glutamyltransferase ( GGT ) and alanine aminotransferase ( ALT ) levels . This pattern was also observed in aspartate aminotransferase ( AST ) quartiles for men but not for women . In multivariate analyses after adjusting for comprehensive risk factors and other liver enzymes , the risk of developing diabetes was significantly higher in the highest GGT quartile than in the lowest quartile [ odds ratio ( OR ) , 2.54 ; 95 % confidence interval ( CI ) , 1.03 to 6.26 for men ; OR , 5.73 ; 95 % CI , 1.62 to 20.19 for women ] . Similar results were observed in ALT quartiles ( OR , 2.32 ; 95 % CI , 0.91 to 5.92 for men ; OR , 4.40 ; 95 % CI , 1.38 to 14.06 for women ) but not in AST quartiles in either sex . Significant positive associations of GGT and ALT with diabetes were seen within each stratified category of risk factors , namely fasting insulin , BMI , waist-to-hip ratio , high-sensitivity C-reactive protein , and alcohol consumption . In receiver operating characteristic analyses , the areas under the receiver operating characteristic curve of GGT and ALT were significantly larger than that of AST , fasting insulin , waist-to-hip ratio , or C-reactive protein . DISCUSSION Our findings suggest that serum GGT and ALT concentrations are strong predictors of diabetes in the general population , independent of known risk factors OBJECTIVE To study the prevalence and determinants of glucose intolerance in a general Caucasian population . RESEARCH DESIGN AND METHODS A r and om sample of 50- to 74-year old Caucasians ( n = 2,484 ) underwent oral glucose tolerance tests . Multiple regression analyses were performed to study the association of 2-h postload plasma glucose values with potential determinants . RESULTS Prevalence of known and newly detected diabetes and impaired glucose tolerance was 3.6 , 4.8 , and 10.3 % , respectively . In women , but not in men , the association of body mass index with 2-h glucose was fully accounted for by the waist-to-hip ratio . Maternal history of diabetes was twice as prevalent as paternal history , but paternal history only was associated with 2-h glucose . In addition , paternal history was a stronger determinant in men than in women . An independent positive association with 2-h plasma glucose was found for alcohol use of > 30 g/day in women and for intake of total protein , animal protein , and polyunsaturated fatty acids in men . An independent inverse association with 2-h plasma glucose was demonstrated for height ( both sexes ) , alcohol use of ≤ 30 g/day ( both sexes ) , energy intake ( in men ) , and , unexpectedly , current smoking ( in men ) . CONCLUSIONS The prevalence of diabetes in elderly Caucasians was 8.3 % . In men , dietary habits may unfavorably influence glucose tolerance independent of obesity OBJECTIVE —The aim of this study was to define the incidence of type 2 diabetes in a low-risk Caucasian population in northern Spain and its association with various risk factors . RESEARCH DESIGN AND METHODS —The Asturias Study is a prospect i ve , population -based survey of diabetes and cardiovascular risk factors . The baseline examination was carried out during 1998–1999 when 1,034 individuals , aged 30–75 years , were r and omly selected to determine the prevalence of type 2 diabetes and pre-diabetes in the Principality of Asturias ( northern Spain ) . In 2004–2005 , these same subjects were invited for a follow-up examination ; 700 participated . This study includes only those individuals who did not have diabetes at baseline . We used the World Health Organization 1999 criteria to classify glucose metabolism at both baseline and follow-up . RESULTS —The incidence of diabetes adjusted for the age and sex structure of Asturias was 10.8 cases/1,000 person-years ( 95 % CI 8.1–14.8 ) . The incidence rates were 5 cases/1,000 person-years in individuals with normoglycemia , 21 cases/1,000 person-years in individuals with isolated impaired glucose tolerance ( IGT ) , 34.7 cases/1,000 person-years in individuals with isolated impaired fasting glucose ( IFG ) , and 95.2 cases/1,000 person-years in individuals with combined IFG-IGT . Stepwise multiple logistic regression analysis showed that , together with fasting plasma glucose ( FPG ) and 2-h plasma glucose , which were the strongest predictors of diabetes , triglycerides and BMI were also independently associated with progression to diabetes . CONCLUSIONS —In this 6-year prospect i ve population -based study , we found an incidence of type 2 diabetes of 10.8 cases/1,000 person-years . Both FPG and 2-h plasma glucose were strongly predictive of diabetes , and their effect was additive Background It has been reported that elevated blood pressure ( BP ) was significantly associated with the increased risk for type 2 diabetes mellitus ( T2DM ) . However , there is still limited information about the influence of BP on the risk for T2DM across the level of glycated hemoglobin ( HbA1c ) . Method In a cohort of the Korean Genome and Epidemiology Study ( KoGES ) , 2830 non-diabetic Korean adults with prediabetes defined by HbA1c level of 5.7–6.4 % were followed-up for 10 years . Multivariate cox proportional hazards assumption was used to assess the risk for T2DM according to the baseline BP categories ( normal , prehypertension and hypertension ) and HbA1c level ( low : 5.7–5.9 % and high : 6.0–6.4 % ) . Results The risk for T2DM significantly increased proportionally to BP categories ( adjusted HR ; reference in normal BP , 1.32 [ 1.10–1.59 ] in prehypertension and 1.61 [ 1.35–1.92 ] in hypertension ) . Subgroup analysis indicated that individuals with high HbA1c had the higher risk for T2DM than individuals with low HbA1c regardless of BP . Additionally , combined presence of hypertension and high HbA1c had the highest risk for T2DM ( adjusted HR : 3.82 [ 3.00–4.87 ] ) . In each systolic and diastolic BP level , the risk for T2DM significantly increased from systolic BP ≥ 130 mmHg ( adjusted HRs : 1.39 ( [ 1.15–1.71 ] ) and diastolic BP ≥ 80 mmHg ( adjusted HRs : 1.30 ( [ 1.07–1.58 ] ) . Conclusion BP and HbA1c may be useful tools in identifying individuals with prediabetes more potentially predisposed to T2DM . Prospect i ve studies should be considered to examine whether controlling BP actually lowers the risk for T2DM Worldwide globalization and Westernization in social and economic aspects have led to drastic changes in South Korea during the past several decades . These changes include individual health behaviours , which were reflected as increased prevalence of non-communicable chronic diseases ( NCDs ) , such as type 2 diabetes mellitus ( T2DM ) , hypertension , obesity and cardiovascular disease ( CVD ) . These NCDs are known to be caused by both environmental risk factors and predisposing genetic factors . Population decline is another issue in South Korea ; the recorded fertility rate was 1.3 births per woman , and 10 % of the population were elderly individuals aged 65 years according to the Population and Housing Census results of 2005 - 2010 . We have also been observing an increased influx and efflux of the population due to globalization . In particular , there has been a rising tendency in the marriage-based inflow of South Asian women during the last decade . To attempt to solve public health issues result ing from these population trends and prepare for personalized and preventive health care in the future , the Korean government ( National Research Institute of Health ( NIH ) , Centers for Disease Control and Prevention and the Ministry of Health and Welfare , Korea ) initiated a large prospect i ve cohort study with government funding , named the Korean genome and epidemiology study ( KoGES ) . The study is a consortium project consisting of six prospect i ve cohort studies that would be categorized into population -based and geneenvironment model studies ( Figure 1 ) . The aim of the KoGES was to establish a genome epidemiological study platform for the research community with a health data base and biobank , to investigate the genetic and environmental aetiology of common complex diseases in Koreans ( i.e. T2DM , hypertension , obesity , metabolic syndrome , osteoporosis , CVD , and cancer ) and causes of death with longterm follow-up . The ultimate goal of the KoGES was to develop comprehensive and applicable health care guidelines for common complex diseases in Koreans , reduce the burden of chronic diseases and improve the quality of life PURPOSE We investigated understudied biomarker-based diabetes among young US adults , traditionally characterized by low cardiovascular disease risk . METHODS We examined 15,701 participants aged 24 to 32 years at Wave IV of the National Longitudinal Study of Adolescent Health ( Add Health , 2008 ) . The study used innovative and relatively noninvasive methods to collect capillary whole blood via finger prick at in-home examinations in all 50 states . RESULTS Assays of dried blood spots produced reliable and accurate values of HbA1c . Reliability was lower for fasting glucose and lowest for r and om glucose . Mean ( SD ) HbA1c was 5.6 % ( 0.8 % ) . More than a quarter ( 27.4 % ) had HbA1c-defined prediabetes . HbA1c was highest in the black , non-Hispanic race/ethnic group , inversely associated with education , and more common among the overweight/obese and physically inactive . The prevalence of diabetes defined by previous diagnosis or use of antidiabetic medication was 2.9 % . Further incorporating HbA1c and glucose values , the prevalence increased to 6.8 % , and among these participants , 38.9 % had a previous diagnosis of diabetes ( i.e. , aware ) . Among those aware , 37.6 % were treated and 64.0 % were controlled ( i.e. , HbA1c < 7 % ) . CONCLUSIONS A contemporary cohort of young adults faces a historically high risk of diabetes but there is ample opportunity for early detection and intervention BACKGROUND It remains controversial whether body mass index ( BMI ) , waist circumference ( WC ) , or waist-hip ratio ( WHR ) is a better risk predictor of type 2 diabetes . OBJECTIVE The objective was to examine the sex-specific relevance of WC , WHR , and BMI to the development of type 2 diabetes . DESIGN The prospect i ve population -based cohort study was based on 3055 men and 2957 women aged 35 - 74 y who participated in the second ( 1989 - 1990 ) or third ( 1994 - 1995 ) MONICA ( Monitoring Trends and Determinants on Cardiovascular Diseases ) Augsburg survey . The subjects were free of diabetes at baseline . Hazard ratios ( HRs ) were estimated from Cox proportional hazards models . RESULTS During a mean follow-up of 9.2 y , 243 cases of incident type 2 diabetes occurred in men and 158 occurred in women . Multivariable-adjusted HRs across quartiles of BMI were 1.0 , 1.37 , 2.08 , and 4.15 in men and 1.0 , 3.77 , 4.95 , and 10.58 in women ; those of WC were 1.0 , 1.15 , 1.57 , and 3.40 in men and 1.0 , 3.21 , 3.98 , and 10.70 in women ; those of WHR were 1.0 , 1.14 , 1.80 , and 2.84 in men and 1.0 , 0.82 , 2.06 , and 3.51 in women . In joint analyses , the highest risk was observed in men and women with a high BMI in combination with a high WC and a high WHR . CONCLUSIONS Both overall and abdominal adiposity were strongly related to the development of type 2 diabetes . Because there was an additive effect of overall and abdominal obesity on risk prediction , WC should be measured in addition to BMI to assess the risk of type 2 diabetes in both sexes Objective The early identification of subjects at high risk for diabetes is essential , thus , r and om rather than fasting plasma glucose is more useful . We aim to evaluate the time interval between pre-diabetes to diabetes with anti-diabetic drugs by using HbA1C as a diagnostic tool , and predicting it using a mathematic model . Methods We used the Taipei Medical University Affiliated Hospital Patient Profile Data base ( AHPPD ) from January-2007 to June-2011 . The patients who progressed and were prescribed anti-diabetic drugs were selected from AHPPD . The mathematical model used to predict the time interval of HbA1C value ranged from 5.7 % to 6.5 % for diabetes progression . Results We predicted an average overall time interval for all participants in between 5.7 % to 6.5 % during a total of 907 days ( st and ard error , 103 days ) . For each group found among 5.7 % to 6.5 % we determined 1169.3 days for the low risk group ( i.e. 3.2 years ) , 1080.5 days ( i.e. 2.96 years ) for the increased risk group and 729.4 days ( i.e. 1.99 years ) for the diabetes group . This indicates the patients will take an average of 2.49 years to reach 6.5 % . Conclusion This prediction model is very useful to help prioritize the diagnosis at an early stage for targeting individuals with risk of diabetes . Using patients ' HbA1C before anti-diabetes drugs are used we predicted the time interval from pre-diabetes progression to diabetes is 2.49 years without any influence of age and gender . Additional studies are needed to support this model for a long term prediction Purpose The Mollerussa prospect i ve cohort was created to study pre-diabetes in a population -based sample from the primary care setting in the semirural area of Pla d’Urgell in Catalonia ( Spain ) . The aims of the study were to assess the prevalence of pre-diabetes in our population , the likelihood to develop overt diabetes over time and to identify risk factors associated with the progression of the condition . Participants The cohort includes 594 subjects r and omly selected between March 2011 and July 2014 from our primary care population , who were older than 25 years , consented to participate and did not have a recorded diagnosis of diabetes . Findings to date At baseline , we performed a clinical interview to collect demographic , clinical and lifestyle ( including a nutritional survey ) characteristics ; carotid ultrasound imaging to assess sub clinical cardiovascular disease was also performed , and a blood sample was collected , with an overall < 5 % rate of missing data . An additional blood draw was performed 12 months after initial recruitment to reassess laboratory results in patients initially identified as having pre-diabetes , with an 89.6 % retention rate . Several studies investigating various hypotheses are currently ongoing . Future plans All subjects recruited during the cohort creation will be followed long-term through annual extraction of data from health records stored in the electronic Clinical station in Primary Care data base . The Mollerussa cohort will thus be a sound population -based sample for multiple future research projects to generate insights into the epidemiology and natural history of pre-diabetes in Spain AIMS To compare the incidence of hyperglycaemia among participants with low , elevated and normal serum thyroid-stimulating hormone concentration , as well as the incidence of abnormal thyroid function test results among participants with normal blood glucose and those with hyperglycaemia . METHODS In a prospect i ve study , a cohort of 72 003 participants with normal , low and elevated serum thyroid-stimulating hormone concentration were followed from the study beginning to the first report of diabetes and prediabetes . A proportional hazards regression model was used to calculate the hazard ratios and 95 % CIs for each outcome , adjusting for age , sex , education level , smoking , alcohol consumption and obesity . Analyses for the association between dysglycaemia and incident abnormal thyroid function test were also conducted . RESULTS During a median 2.6 year follow-up , the incident rates for dysglycaemia , particularly prediabetes , were substantially higher in participants with elevated thyroid-stimulating hormone concentrations at baseline , while the rates for participants with normal and low thyroid-stimulating hormone were similar . After controlling for risk factors , participants with elevated thyroid-stimulating hormone retained a 15 % increase in risk of prediabetes ( adjusted hazard ratio 1.15 , 95 % CI 1.04 - 1.26 ) , but were not at greater risk of diabetes ( adjusted hazard ratio 0.96 , 95 % CI 0.64 - 1.44 ) . By contrast , participants with normal and low thyroid-stimulating hormone concentrations had similar dysglycaemia risks . Participants with diabetes and prediabetes were not at greater risks of developing abnormal thyroid function test results when compared with participants with euglycaemia . CONCLUSIONS People with elevated serum thyroid-stimulating hormone concentration are at greater risk of developing prediabetes . Whether this includes a greater risk of developing frank diabetes may require an extended period of follow-up to clarify Objective To estimate the associations between new-onset hypertension and glycemia , insulin resistance , and overall and regional adiposity in a prospect i ve study conducted in Mauritius . Research design and methods Three thous and five hundred and eighty-one adults without hypertension , pregnancy , or known diabetes at baseline ( 1987 ) were followed for incident hypertension in 1992 and 1998 , ( systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or antihypertensive medication treatment ) . Other measurements included fasting plasma glucose and 2-h plasma glucose after a 75-g oral glucose load , fasting insulin , BMI , waist circumference , smoking , alcohol use , exercise , and demographic information . Insulin sensitivity was estimated by the computerized homeostasis model assessment ( HOMA2 ) program . Results In multivariable logistic models that included age , gender , ethnicity , alcohol use , exercise , education , systolic blood pressure , diastolic blood pressure , homeostasis model assessment , fasting plasma glucose , 2-h plasma glucose , BMI , and waist circumference , the independent predictors of incident hypertension by time of follow-up were ( odds ratio for a 1 SD increase ; 95 % confidence interval ) : 1992 – age ( 1.73 ; 1.47–2.03 ) , Creole ethnicity ( 1.42 ; 1.04–1.94 ) , 2-h plasma glucose ( 1.26 ; 1.04–1.51 ) ; 1998 – age ( 1.60 ; 1.40–1.83 ) and BMI ( 1.33 ; 1.05–1.69 ) . Also , systolic blood pressure and diastolic blood pressure significantly predicted hypertension at both time points . Conclusion Risk factor patterns depended on duration of follow-up . Over 5 years , hypertension was related to 2-h plasma glucose but not to measures of body size or homeostasis model assessment , while over 11 years , incident hypertension was related to BMI but not waist circumference , 2-h plasma glucose , or homeostasis model assessment . These findings support a more important role for 2-h plasma glucose and overall adiposity than waist circumference , fasting plasma glucose , or insulin resistance in the development of hypertension in Mauritius BACKGROUND An association between diabetes mellitus ( DM ) and cancer has long been speculated , but no conclusive evidence has been obtained . METHODS We prospect ively examined the association between a history of DM and subsequent risk of cancer in the Japan Public Health Center-Based Prospect i ve Study . A total of 97 771 general Japanese persons ( 46 548 men and 51 223 women ) aged 40 to 69 years who responded to the baseline question naire , from January 1990 to December 1994 , were followed up for cancer incidence through December 31 , 2003 . At baseline , 6.7 % of men and 3.1 % of women had a history of DM . RESULTS A total of 6462 cases of newly diagnosed cancer were identified . In men , a 27 % increase in the risk of total cancer incidence was observed in those with a history of DM ( n = 3907 [ 366 with DM ] ; hazard ratio [ HR ] , 1.27 ; 95 % confidence interval [ CI ] , 1.14 - 1.42 ) . The HR was especially high for those with cancer of the liver ( n = 312 [ 52 with DM ] ; HR , 2.24 ; 95 % CI , 1.64 - 3.04 ) , pancreas ( n = 118 [ 16 with DM ] ; HR , 1.85 ; 95 % CI , 1.07 - 3.20 ) , and kidney ( n = 99 [ 13 with DM ] ; HR , 1.92 ; 95 % CI , 1.06 - 3.46 ) . We also observed a moderately increased risk of colon cancer ( n = 491 [ 46 with DM ] ; HR , 1.36 ; 95 % CI , 1.00 - 1.85 ) and of stomach cancer with borderline significance ( n = 977 [ 87 with DM ] ; HR , 1.23 ; 95 % CI , 0.98 - 1.54 ) . In women , a borderline significant increase in risk was observed for the incidence of total cancer ( n = 2555 [ 104 with DM ] ; HR , 1.21 ; 95 % CI , 0.99 - 1.47 ) , while statistical significance was observed for the incidence of stomach cancer ( n = 362 [ 20 with DM ] ; HR , 1.61 ; 95 % CI , 1.02 - 2.54 ) and liver cancer ( n = 120 [ 10 with DM ] ; HR , 1.94 ; 95 % CI , 1.00 - 3.73 ) and borderline significance was observed for the incidence of ovarian cancer ( n = 74 [ 5 with DM ] ; HR , 2.42 ; 95 % CI , 0.96 - 6.09 ) . CONCLUSION Patients with DM drawn from the general Japanese population may be at increased risk of total cancer and of cancer in specific sites The objective was to assess whether pediatric risk factors predict cardiovascular disease ( CVD ) , impaired fasting glucose ( IFG ) + type 2 diabetes mellitus ( T2DM ) , and high blood pressure ( HBP ) in young adulthood . We performed a prospect i ve follow-up of 909 public-parochial suburban schoolchildren first studied at ages 6 to 18 years and 26 years later at a mean age of 38 years . Pediatric triglycerides ( TGs ) , blood pressure , low-density lipoprotein cholesterol , body mass index , and glucose above and high-density lipoprotein cholesterol below established pediatric cutoffs , along with race , cigarette smoking , family history of CVD , T2DM , and HBP , were assessed as determinants of young adult CVD , a composite variable including IFG + T2DM and HBP . By stepwise logistic regression , adult CVD ( 19 yes , 862 no ) was associated with pediatric high TG ( odds ratio [ OR ] , 5.85 ; 95 % confidence interval [ CI ] , 2.3 - 14.7 ) . High TG in pediatric prob and s with young adult CVD was familial and was associated with early CVD in their high-TG parents . Adult IFG + T2DM ( 114 yes , 535 no ) was associated with parental T2DM ( OR , 2.2 ; 95 % CI , 1.38 - 3.6 ) , high childhood glucose ( OR , 4.43 ; 95 % CI , 2 - 9.7 ) , and childhood cigarette smoking ( OR , 1.64 ; 95 % CI , 1.03 - 2.61 ) . Adult HBP ( 133 yes , 475 no ) was associated with pediatric high body mass index ( OR , 2.7 ; 95 % CI , 1.7 - 4.3 ) and HBP ( OR , 2.5 ; 95 % CI , 1.5 - 4.3 ) . Pediatric risk factors are significantly , independently related to young adult CVD , IFG + T2DM , and HBP . Identification of pediatric risk factors for CVD , IFG + T2DM , and HBP facilitates initiation of primary prevention programs to reduce development of adult CVD , IFG + T2DM , and HBP Risk factors associated with the progression from impaired glucose tolerance ( IGT ) to NIDDM were examined in data from six prospect i ve studies . IGT and NIDDM were defined in all studies by World Health Organization ( WHO ) criteria , and baseline risk factors were measured at the time of first recognition of IGT . The studies varied in size from 177 to 693 participants with IGT , and included men and women followed from 2 to 27 years after the recognition of IGT . Across the six studies , the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years . Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence , incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels , but increased linearly with increasing 2-h postchallenge glucose quartiles . Incidence rates were higher among the Hispanic , Mexican-American , Pima , and Nauruan population s than among Caucasians . The effect of baseline age on NIDDM incidence rates differed among the studies ; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies . In all studies , estimates of obesity ( including BMI , waist-to-hip ratio , and waist circumference ) were positively associated with NIDDM incidence . BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately , but not in the three studies with the highest NIDDM incidence rates . Sex and family history of diabetes were generally not related to NIDDM progression . This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements . The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention OBJECTIVE To describe the characteristics and vital prognosis of men with diabetes diagnosed by one fasting plasma glucose ( FPG ) concentration > or = 7.0 mmol/l , with diabetes diagnosed by one isolated postchallenge hyperglycemia ( IPH ) ( FPG < 7.0 mmol/l and a 2-h plasma glucose concentration > or = 11.1 mmol/l ) , or with impaired glucose tolerance ( IGT ) . RESEARCH DESIGN AND METHODS This study involved a cohort of 6,881 Caucasian nondiabetic men from the Paris Prospect i ve Study , aged 44 - 55 years , who were followed for cause of death for 20 years . RESULTS Diabetes was diagnosed in 4.3 % of the men ( 1.0 % diabetes diagnosed by IPH ) , and IGT was diagnosed in 9 % of the men . At baseline , the men with diabetes diagnosed by IPH had a lower cardiovascular risk profile than those with diabetes diagnosed by FPG , as did the men with IGT and a normal fasting glucose level ( < 6.1 mmol/l , IGT and normal fasting glucose ) , compared with men with impaired fasting glucose ( 6.1 - 6.9 mmol/l , IGT and impaired fasting glucose [ IFG ] ) . At 20 years of follow-up , all-cause and cancer death rates were higher in men with diabetes diagnosed by IPH than in men with diabetes diagnosed by FPG ( 55 vs. 44 % , P < 0.1 and 31 vs. 17 % , P < 0.01 , respectively ) but were not significantly different for coronary causes ( 6 vs. 11 % ) . Men with IGT and normal fasting glucose also had significantly higher cancer death rates than men with IGT and IFG . CONCLUSIONS The most likely explanation for the high cancer and low coronary death rates is that men with diabetes diagnosed by IPH consumed alcohol ; the men in this study drank 49 g of pure alcohol on average per day , equivalent to 0.6 l of wine . If these results are confirmed by other prospect i ve studies , screening subjects for isolated postchallenge hyperglycemia may not be worthwhile OBJECTIVE We prospect ively assessed whether the combined measurements of fasting plasma glucose ( FPG ) and A1C were effective for predicting type 2 diabetes . RESEARCH DESIGN AND METHODS Study participants included 6,736 nondiabetic Japanese men aged 40–55 years . Type 2 diabetes was diagnosed in those who had an FPG ≥126 mg/dl or who were being treated with an oral antidiabetic agent or insulin . The models including FPG , A1C , and both were compared using the area under the receiver operating characteristic ( AUROC ) curves . RESULTS During the 4-year follow-up period , we confirmed 659 diabetes cases . In multivariate analysis , both FPG and A1C were independently associated with the risk of type 2 diabetes . The model including both FPG and A1C had a greater AUROC curve than that including FPG alone ( 0.853 vs. 0.818 ; P < 0.001 ) or A1C alone ( 0.853 vs. 0.771 ; P < 0.001 ) . CONCLUSIONS The combined measurement of FPG and A1C was effective for predicting type 2 diabetes Aims /hypothesis Evidence has suggested that low serum potassium concentrations decrease insulin secretion , leading to glucose intolerance , and that hypokalaemia induced by diuretics increases the risk for diabetes in hypertensive individuals . However , no prospect i ve study has investigated the association between serum potassium and the development of type 2 diabetes in a healthy cohort comprised of Asian individuals not being administered antihypertensive medications . This study aim ed to investigate whether low serum potassium is associated with increased risk of type 2 diabetes in apparently healthy Japanese men . Methods We followed 4,409 Japanese men with no history of diabetes , use of antihypertensives , renal dysfunction or liver dysfunction ( mean ± SD age , 48.4 ± 8.4 years ) . Cox proportional hazards regression was used to estimate HRs for incident diabetes ( fasting plasma glucose level ≥7.0 mmol/l , HbA1c ≥ 6.5 % or self-reported ) including serum potassium concentration as either a categorical or a continuous variable . Results During a 5 year follow-up , 250 individuals developed type 2 diabetes . The lowest tertile of serum potassium ( 2.8–3.9 mmol/l ) was independently associated with the development of diabetes after adjustment for known predictors ( HR 1.57 [ 95 % CI , 1.15–2.15 ] ) compared with the highest tertile ( 4.2–5.4 mmol/l ) . Every 0.5 mmol/l lower increment in the baseline serum potassium level was associated with a 45 % ( 12–87 % ) increased risk of diabetes . Conclusions /interpretationMild to moderately low serum potassium levels , within the normal range and without frank hypokalaemia , could be predictive of type 2 diabetes in apparently healthy Japanese men Abstract The competing risk method has become more acceptable for time-to-event data analysis because of its advantage over the st and ard Cox model in accounting for competing events in the risk set . This study aim ed to construct a prediction model for diabetes using a subdistribution hazards model . We prospect ively followed 1857 community residents who were aged ≥ 55 years , free of diabetes at baseline examination from August 1992 to December 2012 . Diabetes was defined as a self-reported history of diabetes diagnosis , taking antidiabetic medicine , or having fasting plasma glucose ( FPG ) ≥ 7.0 mmol/L. A question naire was used to measure diabetes risk factors , including dietary habits , lifestyle , psychological factors , cognitive function , and physical condition . Gray test and a subdistribution hazards model were used to construct a prediction algorithm for 20-year risk of diabetes . Receiver operating characteristic ( ROC ) curves , bootstrap cross-vali date d Wolber concordance index ( C-index ) statistics , and calibration plots were used to assess model performance . During the 20-year follow-up period , 144 cases were documented for diabetes incidence with a median follow-up of 10.9 years ( interquartile range : 8.0–15.3 years ) . The cumulative incidence function of 20-year diabetes incidence was 11.60 % after adjusting for the competing risk of nondiabetes death . Gray test showed that body mass index , FPG , self-rated heath status , and physical activity were associated with the cumulative incidence function of diabetes after adjusting for age . Finally , 5 st and ard risk factors ( poor self-rated health status [ subdistribution hazard ratio ( SHR ) = 1.73 , P = 0.005 ] , less physical activity [ SHR = 1.39 , P = 0.047 ] , 55–65 years old [ SHR = 4.37 , P < 0.001 ] , overweight [ SHR = 2.15 , P < 0.001 ] or obesity [ SHR = 1.96 , P = 0.003 ] , and impaired fasting glucose [ IFG ] [ SHR = 1.99 , P < 0.001 ] ) were significantly associated with incident diabetes . Model performance was moderate to excellent , as indicated by its bootstrap cross-vali date d discrimination C-index ( 0.74 , 95 % CI : 0.70–0.79 ) and calibration plot . Poor self-rated health , physical inactivity , being 55 to 65 years of age , overweight/obesity , and IFG were significant predictors of incident diabetes . Early prevention with a goal of achieving optimal levels of all risk factors should become a key element of diabetes prevention OBJECTIVE We have previously suggested using the paired values of fasting plasma glucose ( FPG ) and HbA1c to identify potential diabetic subjects . In this article , we followed up on 208 nondiabetic subjects and examined their rates of progression to diabetes . We analyzed their likelihood of becoming diabetic according to their baseline FPG and HbA1c concentrations . RESEARCH DESIGN AND METHODS Between 1988 and 1995 , 2,877 Chinese subjects with risk factors for diabetes underwent screening . Of these , 2,250 had FPG < 7.8 mmol/l and 2-h plasma glucose ( PG ) < 11.1 mmol/l . Of these 2,250 subjects , 265 were r and omly recruited for an annual oral glucose tolerance test ( OGTT ) until they progressed to develop diabetes . Of those 265 subjects , 57 had baseline FPG > or = 7.0 mmol/l and were excluded from the present analysis . Hence , the progression of glucose tolerance in 208 subjects who were nondiabetic according to the new American Diabetes Association diagnostic criteria ( FPG < 7.0 mmol/l and 2-h PG < 11.1 mmol/l ) was examined RESULTS Of the 208 nondiabetic subjects , 26 ( 12.5 % ) were men and 182 ( 87.5 % ) were women . After a mean follow-up of 1.60 + /- 1.16 years ( range 1 - 7 , median 1 ) , 44 ( 21.2 % ) progressed to develop diabetes and 164 ( 78.8 % ) remained nondiabetic . Those who were diabetic at the end of the study had a high likelihood ratio ( LR ) of 9.3 to have baseline FPG > or = 6.1 mmol/l and baseline HbA1c > or = 6.1 % . This was compared with a low LR of 0.6 - 1.1 in diabetic subjects who had either FPG < 6.1 mmol/l or HbA1c < 6.1 % or both at baseline . The crude rate of progression to diabetes was more than five times higher ( 44.1 vs. 8.1 % ) in those whose baseline FPG was > or = 6.1 mmol/l and baseline HbA1c was > or = 6.1 % compared with those whose baseline FPG was < 6.1 mmol/l and baseline HbA1c was < 6.1 % . CONCLUSIONS For Chinese subjects with risk factors for glucose intolerance , the use of paired FPG and HbA1c values helped to identify potential diabetic subjects . Those with an FPG > or = 6.1 mmol/l and HbA1c > or = 6.1 % had a rate of progression to diabetes more than five times higher than those with an FPG < 6.1 mmol/l and an HbA1c < 6.1 % after a mean follow-up of 1.6 years . Those with an FPG > or = 6.1 but < 7.0 mmol/l , especially if their HbA1c was > or = 6.1 % , should undergo an OGTT to confirm diabetes . Subjects with an FPG < 6.1 mmol/l and /or an HbA1c < 6.1 % should have regular screening using the paired values of FPG and HbA1c Aims /hypothesisWe sought to identify determinants of progression from impaired fasting glucose ( IFG ) and impaired glucose tolerance ( IGT ) to diabetes in high-risk screened individuals . Methods In general practice s in Denmark , stepwise screening for type 2 diabetes mellitus in persons aged 40 to 69 years included a risk question naire , r and om blood glucose , HbA1c , fasting blood glucose and an OGTT . The 1,821 individuals with IGT or isolated IFG ( WHO 1999 ) were re-invited after 1 and 3 years . Follow-up data on glucose measurements were available in 1,510 individuals and additional clinical data in 1,002 collected at the 3-year visits . Regression models using interval censoring were used . Results Progression rates from IFG and IGT to diabetes over 3.5 years were 11.8 and 17.0 per 100 person-years , respectively and were particularly high in the first year . Baseline determinants of progression were : IFG : glucose measures , BMI [ per kg/m2 , rate ratio ( RR ) 1.04 ( 95 % CI , 1.01–1.08 ) ] and triacylglycerol [ per twofold increase , RR 2.19 ( 1.49–3.22 ) ] ; and IGT : glucose measures and known hypertension [ RR 1.46 ( 1.11–1.93 ) ] . Weight reduction and decreased triacylglycerol were inversely associated with development of diabetes in IFG individuals [ per 1 kg/year , RR 0.81 ( 0.66–0.98 ) and per 1 mmol l−1 year−1 , RR 0.08 ( 0.01–0.51 ) , respectively ] , whereas in IGT participants only weight reduction was inversely associated [ per 1 kg/year , RR 0.80 ( 0.67–0.96 ) ] . Conclusions /interpretationHigher levels of glucose measures , larger BMI , known hypertension and hypertriacylglycerolaemia are significant determinants of progression in high-risk screened individuals . Weight loss of 1 kg/year or reduction of hypertriacylglycerolaemia markedly reduced the risk of diabetes AIMS We examined the optimal cut-off values of fasting plasma glucose , 2-h post-load glucose and HbA(1c ) for predicting Type 2 diabetes in community-dwelling Japanese subjects . METHODS A total of 1982 subjects without diabetes aged 40 - 79 years who underwent a 75-g oral glucose tolerance test were followed prospect ively for 14 years by annual health examination . RESULTS During the follow-up , 295 subjects developed Type 2 diabetes . Compared with the first decile , the crude hazard ratio for incident Type 2 diabetes was significantly higher in the fifth fasting plasma glucose decile [ 5.4 - 5.4 mmol/l ( 97 - 98 mg/dl ) ] or higher , in the seventh 2-h post-load glucose decile [ 6.9 - 7.2 mmol/l ( 124 - 131 mg/dl ) ] or higher , and in the fifth HbA(1c ) decile [ 34 - 36 mmol/mol ( 5.3 - 5.4 % ) ] or higher . These associations remained substantially unchanged even after adjustment for confounding factors . The receiver operating characteristic curve analysis showed that the optimal cut-off values for predicting Type 2 diabetes were 5.6 mmol/l ( 101 mg/dl ) for fasting plasma glucose , 6.9 mmol/l ( 124 mg/dl ) for 2-h post-load glucose and 37 mmol/mol ( 5.5 % ) for HbA(1c ) . In a stratified analysis , the cut-off values were approximately 5.6 mmol/l ( 101 mg/dl ) for fasting plasma glucose and 37 mmol/mol ( 5.5 % ) for HbA(1c ) , and these values were unchanged over BMI quartile levels , whereas the 2-h post-load glucose cut-off values declined with decreasing BMI levels . CONCLUSIONS Our findings suggest that the cut-off value for predicting Type 2 diabetes in the Japanese population is 5.6 mmol/l ( 101 mg/dl ) for fasting plasma glucose and 37 mmol/mol ( 5.5 % ) for HbA(1c ) , while the 2-h post-load glucose cut-off value is lower than the diagnostic criterion for impaired glucose tolerance Previous studies have indicated that beta-cell dysfunction predicts the development of diabetes , although it is unknown whether the use of combinations of insulin secretory measures further improves prediction . The Insulin Resistance Atherosclerosis Study is a prospect i ve , multicenter , epidemiological study of the relationship between insulin sensitivity and the risk of diabetes and cardiovascular disease . At baseline , fasting concentrations of insulin , intact proinsulin ( PI ) , and split PI were measured , and acute insulin response ( AIR ) was determined during a frequently sample d intravenous glucose tolerance test ( FSIGTT ) . Subjects who were nondiabetic at baseline ( n = 903 ) were reexamined after 5 years of follow-up ; 148 had developed diabetes . In separate logistic regression models adjusted for age , sex , clinic , and ethnicity , 1 SD differences in measures of beta-cell dysfunction were associated with diabetes incidence ( AIR : odds ratio [ OR ] 0.37 , 95 % CI 0.27 - 0.52 ; intact PI : OR 1.90 , 95 % CI 1.57 - 2.30 ; split PI : OR 1.94 , 95 % CI 1.63 - 2.31 ) . After additional adjustment for BMI , impaired glucose tolerance , and insulin sensitivity , these measures continued to be significantly associated with risk of diabetes ( all P < 0.0001 ) . Furthermore , in models that included both PI and AIR , each was an independent predictor , and individuals who had combined low AIR and high PI experienced the highest diabetes risk . In conclusion , both low AIR and high PI independently predicted diabetes in a well-characterized multiethnic population . Although fasting PI is simpler to assess , determining AIR from an FSIGTT may further improve prediction . If pharmacological agents to prevent diabetes are proved to be efficacious in ongoing clinical trials , then it may be beneficial to perform FSIGTTs to identify better ( for intensive intervention ) prediabetic subjects who would ultimately require lifelong pharmacological therapy OBJECTIVE To examine the association between low to moderate alcohol consumption and the incidence of type 2 diabetes mellitus ( DM ) in men . DESIGN Prospect i ve cohort study . SUBJECTS AND METHODS Over an average period of 12.1 years , we evaluated 20 951 participants in the Physicians ' Health Study between ages 40 and 84 years who were free of cardiovascular disease , cancer , and diabetes and provided data on alcohol consumption at baseline . MAIN OUTCOME MEASURE Type 2 DM diagnosed after r and omization . RESULTS Among 20 951 physicians , 766 cases of incident DM were reported over an average follow-up period of 12.1 years . After adjustment for age , r and omized treatment assignment , smoking , physical activity , and body mass index , the relative risk estimates and 95 % confidence intervals for those reporting alcohol use of rarely/ never , 1 to 3 drinks per month , 1 drink per week , 2 to 4 drinks per week , 5 to 6 drinks per week , and 1 or more drinks per day were 1.00 ( referent ) , 1.03 ( 0.80 - 1.33 ) , 0.89 ( 0.70 - 1.14 ) , 0.74 ( 0.59 - 0.93 ) , 0.67 ( 0.51 - 0.89 ) , and 0.57 ( 0.45 - 0.73 ) , respectively ( linear trend , P<.001 ) . Additional adjustment for baseline history of hypertension , high cholesterol level , or parental history of myocardial infa rct ion or family history of diabetes ( data collected at 9 years ) did not material ly alter the results . These associations persisted in analyses stratified by age , smoking status , body mass index , physical activity , and family history of DM . CONCLUSION These data indicate that apparently healthy men who self-select for light to moderate alcohol consumption have a decreased subsequent risk of type 2 DM Abstract Aims /hypothesis . We examined whether the 2-h plasma glucose ( 2hPG ) concentration after a 75 g OGTT is predictive of death in men with a diabetic , an impaired or a normal fasting plasma glucose concentration ( DM-FPG : ≥7.0 mmol/l ; IFG : 6.1–6.9 mmol/l ; normal-FPG : < 6.1 mmol/l ) . Methods . The 17-year mortality of 7018 men , aged 44 to 55 years , from the Paris Prospect i ve Study , who were not known to be diabetic at baseline was studied . Results . The 2hPG was not associated with early mortality in men with a DM-FPG in contrast to men with an IFG or a normal-FPG ; for an increase from 10 to 11 mmol/l in the 2hPG , the age-adjusted hazards ratios were 1.01 ( 95 % CI 0.95–1.08 ) , 1.15 ( 1.03–1.28 ) and 1.24 ( 1.18–1.31 ) respectively . Coronary heart disease mortality and within this category sudden death but not ischaemic heart disease death , were related with 2hPG but only in the men with normal FPG . However , the prediction by 2hPG did not differ between the men with DM-FPG , an IFG or a normal-FPG : the overall age-adjusted hazards ratios for these three causes of death were 1.09 ( 1.00–1.18 ) , 1.13 ( 1.02–1.26 ) and 1.13 ( 0.99–1.29 ) , respectively . Conclusion /interpretation . 2hPG is unequivocally prognostic for all-cause mortality only in men with normal FPG . Screening men with an IFG by using a 75 g OGTT is of limited benefit OBJECTIVE Individuals with diabetes mellitus ( DM ) have a considerably elevated risk of developing serious health problems including cardiovascular disease ( CVD ) . Long-term elevated levels of blood glucose in nondiabetic individuals may also be associated with increased risk of CVD . The aim of this study was to investigate the relationships between glycated haemoglobin A(1c ) ( HbA(1c ) ) and CVD , DM and all-cause mortality . SUBJECTS AND DESIGN The Copenhagen City Heart Study is a prospect i ve study of individuals from the Danish general population . The cohort was followed for 10 years via national registers with respect to incident CVD , DM and all-cause mortality . Follow-up was 100 % complete . RESULTS A total of 5127 subjects were included , of whom 597 had DM . In the nondiabetic population , HbA(1c ) was significantly associated with incident CVD events in both univariate [ hazard ratio ( HR ) 1.38 , 95 % CI 1.11 - 1.71 ] and multivariate analyses ( HR 1.31 , 95 % CI 1.05 - 1.64 ) . In the nondiabetic population , increased levels of HbA(1c ) were correlated with developing DM . There was a threefold increase in risk of incident DM per unit increase in HbA(1c ) with a univariate HR of 3.83 ( 95 % CI 1.96 - 7.51 ) . This relationship was essentially unchanged after multivariate adjustments ( HR 4.19 , 95 % CI 2.01 - 8.71 ) . Furthermore , we found that net reclassification improvement for diagnosed DM and CVD was significantly improved with the addition of HbA(1c ) in the analyses . Although not statistically significant , we found a strong trend towards an association between HbA(1c ) and all-cause mortality ( HR 1.21 , 95 % CI 0.99 - 1.47 ) . We did not find the same associations amongst the population with DM . CONCLUSION In the Danish general population , HbA(1c ) was strongly associated with CVD in individuals without DM Aims /hypothesisTo estimate the prevalence of undiagnosed diabetes mellitus , impaired glucose tolerance ( IGT ) and impaired fasting glucose ( IFG ) , and their relations with cardiovascular risk factors in the general population aged 55 to 74 years in Southern Germany . Methods Oral glucose tolerance tests were carried out in a r and om sample of 1353 subjects aged 55 to 74 years participating in the KORA ( Cooperative Health Research in the Region of Augsburg ) Survey 2000 . Prevalences of glucose tolerance categories ( 1999 WHO criteria ) were adjusted for sample probabilities . The numbers needed to screen ( NNTS ) to identify one person with undiagnosed diabetes were estimated from age-adjusted logistic regression models . Results Sample design -based prevalences of known and unknown diabetes , IGT , and IFG were 9.0 % , 9.7 % , 16.8 % , 9.8 % in men , and 7.9 % , 6.9 % , 16.0 % , 4.5 % in women , respectively . In both sexes , participants with undiagnosed diabetes had higher BMI , waist circumference , systolic blood pressure , triglycerides , uric acid , and lower HDL-cholesterol than normoglycaemic subjects . A combination of abdominal adiposity , hypertension , and parental diabetes in men result ed in a NNTS of 2.9 ( 95%CI : 2.0–4.6 ) . In women , the combination of increased triglycerides , hypertension and parental diabetes history yielded a NNTS of 3.2 ( 95%CI : 2.2–5.1 ) . Conclusion /interpretationAbout 40 % of the population aged 55 to 74 years in the Augsburg region have disturbed glucose tolerance or diabetes . Half of the total cases with diabetes are undiagnosed . Cardiovascular risk factors worsen among glucose tolerance categories , indicating the need for screening and prevention . Screening for undiagnosed diabetes could be most efficient in individuals with abdominal adiposity ( men ) , hypertriglyceridaemia ( women ) , hypertension , and parental diabetes history BACKGROUND Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes . We aim ed to characterise trajectories of fasting and postload glucose , insulin sensitivity , and insulin secretion in individuals who develop type 2 diabetes . METHODS We analysed data from our prospect i ve occupational cohort study ( Whitehall II study ) of 6538 ( 71 % male and 91 % white ) British civil servants without diabetes mellitus at baseline . During a median follow-up period of 9.7 years , 505 diabetes cases were diagnosed ( 49.1 % on the basis of oral glucose tolerance test ) . We assessed retrospective trajectories of fasting and 2-h postload glucose , homoeostasis model assessment ( HOMA ) insulin sensitivity , and HOMA beta-cell function from up to 13 years before diabetes diagnosis ( diabetic group ) or at the end of follow-up ( non-diabetics ) . FINDINGS Multilevel models adjusted for age , sex , and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics ( 10,989 measurements ) , except for insulin secretion that did not change during follow-up . In the diabetic group ( 801 measurements ) , a linear increase in fasting glucose was followed by a steep quadratic increase ( from 5.79 mmol/L to 7.40 mmol/L ) starting 3 years before diagnosis of diabetes . 2-h postload glucose showed a rapid increase starting 3 years before diagnosis ( from 7.60 mmol/L to 11.90 mmol/L ) , and HOMA insulin sensitivity decreased steeply during the 5 years before diagnosis ( to 86.7 % ) . HOMA beta-cell function increased between years 4 and 3 before diagnosis ( from 85.0 % to 92.6 % ) and then decreased until diagnosis ( to 62.4 % ) . INTERPRETATION In this study , we show changes in glucose concentrations , insulin sensitivity , and insulin secretion as much as 3 - 6 years before diagnosis of diabetes . The description of biomarker trajectories leading to diabetes diagnosis could contribute to more-accurate risk prediction models that use repeated measures available for patients through regular check-ups . FUNDING Medical Research Council ( UK ) ; Economic and Social Research Council ( UK ) ; British Heart Foundation ( UK ) ; Health and Safety Executive ( UK ) ; Department of Health ( UK ) ; National Institute of Health ( USA ) ; Agency for Health Care Policy Research ( USA ) ; the John D and Catherine T MacArthur Foundation ( USA ) ; and Academy of Finl and ( Finl and ) AIMS The aim of this work was to determine the cumulative incidence and independent risk factors of prediabetes and type 2 diabetes ( T2DM ) in a well-characterized cohort of Malays in Singapore . METHODS We included 1137 participants ( mean age [ SD ] : 55 ( 10 ) years ; 53.6 % female ) without diabetes ( DM ) at baseline from the Singapore Malay Eye Study , a population -based longitudinal study with baseline ( 2004 - 2006 ) , and follow-up ( 2010 - 2013 ) examinations . Prediabetes was defined as an HbA1c between 5.7 % and 6.4 % , with no self-reported DM history or insulin/DM medication use . T2DM was defined as a r and om glucose level ≥200mg/dL or HbA1c>6.4 % or use of insulin/DM medication . Age-st and ardized cumulative incidence was calculated as the crude 6-year cumulative incidence st and ardized to Singapore 's Malay population census . Multivariable modified poisson regression models were utilized to determine the risk factors of incident prediabetes and T2DM . RESULTS The age-st and ardized 6-year cumulative incidence was 11.2 % ( 95 % CI 9.5 , 13.1 % ) for T2DM , and 20.4 % ( 95 % CI 16.4 , 25.2 % ) for prediabetes . Hypertension , higher body mass index ( BMI ) and higher Hba1c levels were associated with increased risk of T2DM , while older age and higher high density lipoprotein ( HDL ) cholesterol were protective ( all P<0.05 ) . Only higher BMI and HbA1c levels were independently associated with incident prediabetes ( all P≤0.001 ) . CONCLUSIONS While only one in ten adult Malays developed T2DM over 6-years , one in five developed prediabetes over the same time period . Our results suggest that evidence -based interventions addressing modifiable risk factors ( obesity , prediabetes , hypertension , low HDL cholesterol ) are needed to delay or prevent their onset AIM To investigate the performance of HbA1c in predicting incident diabetes among Korean adults with normal fasting glucose and impaired fasting glucose levels . METHODS This study used data from the Korean Genome Epidemiology Study -Kangwha Study . A prospect i ve analysis was carried out on 2079 people ( 820 men and 1259 women ) who completed follow-up examinations up until 2013 . Diabetes was defined as fasting blood glucose level ≥ 7.0 mmol/l , HbA1c level ≥ 48 mmol/mol ( 6.5 % ) , or current treatment for diabetes . Areas under the receiver-operating characteristic curves were used to assess the different performances of HbA1c , glucose and insulin in predicting diabetes . RESULTS The median follow-up time was 3.97 years , during which 7.7 % of men and 6.3 % of women developed incident diabetes . The areas under the receiver-operating curves ( 95 % CI ) for diabetes prediction were 0.740 ( 0.692 - 0.787 ) for HbA1c , 0.716 ( 0.667 - 0.764 ) for glucose and 0.598 ( 0.549 - 0.648 ) for insulin . HbA1c showed better predictive power in people with impaired fasting glucose ( area under the curve 0.753 , 95 % CI 0.685 - 0.821 ) than in those with normal glucose ( area under the curve 0.648 , 95 % CI 0.577 - 0.719 ) . An HbA1c threshold of 40 mmol/mol ( 5.8 % ) was found to have the highest predictive value for diabetes , with a relative risk of 6.30 ( 95 % CI 3.49 - 11.35 ) in men and 3.52 ( 95 % CI 2.06 - 6.03 ) in women after adjusting for age , waist circumference , triglycerides , hypertension , family history of diabetes , smoking , alcohol intake , exercise and baseline glucose level . CONCLUSIONS HbA1c can be used to identify people at high risk for the development of diabetes , especially in those with impaired fasting glucose levels The purpose of this study was to estimate the prevalence of type 2 diabetes and impaired fasting glucose ( IFG ) in Penghu , Taiwan and compare these estimates with those of the US ( NHANES III ) . Diabetes and IFG ( American Diabetes Association criteria , 1997 ) were assessed among a stratified r and om sample of 2500 residents of Penghu Isl and s , Taiwan . The prevalence ( age-adjusted to world adult population ) of diabetes and IFG were 16.8 % ( 95 % CI 15.0 - 18.6 ) and 21.0 % ( 95 % CI 19.0 - 23.0 ) , respectively , among Penghu Isl and ers in Taiwan . Age sex-specific diabetes prevalence ranged from 10.0 % in men aged 40 - 49 years to 29.4 % in women aged 60 - 69 years . Prevalence of IFG ranged from 14.7 % in women aged 40 - 49 years to 30.7 % in men aged 50 - 59 years . Age , body mass index ( BMI ) , and family history of diabetes were each independently associated with both diabetes and IFG . In addition , female gender , apolipoprotein B and triglyceride concentrations were associated with diabetes , and hypertension and apolipoprotein B concentration with IFG . Among persons > or = 40 years in Penghu , Taiwan , the prevalence of diabetes is up to a third higher and the prevalence of IFG is up to three times higher than comparably aged Americans , despite their having a mean BMI 2.2 - 3.2 kg/m2 lower than Americans . The alarmingly high prevalence of IFG in Taiwan may indicate an emerging diabetes epidemic A prospect i ve study was undertaken in 107 Indians with impaired glucose tolerance ( IGT ) for a period ranging from 2 to 10 years . On follow-up , 32 % still had an impaired glucose tolerance , 32 % reverted to normal glucose tolerance and 36 % developed diabetes . Careful dietary adherence and weight reduction were found to favour normalisation of glucose tolerance . Poor dietary adherence , persistent obesity and weight gain were found to precipitate diabetes . The study stresses the need for intensive diet therapy in individuals with IGT . Insulin responses were heterogeneous in IGT and non-predictive of the follow-up changes in glucose tolerance Abstract Objective : To examine the value of glycated haemoglobin ( HbA1c ) concentration , a marker of blood glucose concentration , as a predictor of death from cardiovascular and all causes in men . Design : Prospect i ve population study . Setting : Norfolk cohort of European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Norfolk ) . Subjects : 4662 men aged 45 - 79 years who had had glycated haemoglobin measured at the baseline survey in 1995 - 7 who were followed up to December 1999 . Main outcome measures : Mortality from all causes , cardiovascular disease , ischaemic heart disease , and other causes . Results : Men with known diabetes had increased mortality from all causes , cardiovascular disease , and ischaemic disease ( relative risks 2.2 , 3.3 , and 4.2 , respectively , P < 0.001 independent of age and other risk factors ) compared with men without known diabetes . The increased risk of death among men with diabetes was largely explained by HbA1c concentration . HbA1c was continuously related to subsequent all cause , cardiovascular , and ischaemic heart disease mortality through the whole population distribution , with lowest rates in those with HbA1c concentrations below 5 % . An increase of 1 % in HbA1c was associated with a 28 % ( P<0.002 ) increase in risk of death independent of age , blood pressure , serum cholesterol , body mass index , and cigarette smoking habit ; this effect remained ( relative risk 1.46 , P=0.05 adjusted for age and risk factors ) after men with known diabetes , a HbA1c concentration ≥7 % , or history of myocardial infa rct ion or stroke were excluded . 18 % of the population excess mortality risk associated with a HbA1c concentration ≥5 % occurred in men with diabetes , but 82 % occurred in men with concentrations of 5%-6.9 % ( the majority of the population ) . Conclusions : Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution . Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA1c through behavioural means Purpose To examine the longitudinal associations of serum fatty acid composition with type 2 diabetes , insulin secretion and insulin sensitivity over several years . Methods We conducted a prospect i ve cohort study derived from the r and omized Finnish Diabetes Prevention Study . Total serum fatty acid composition was measured using gas chromatography in 407 overweight , middle-aged people with impaired glucose tolerance at baseline ( 1993–1998 ) and annually during the intervention period ( 1994–2000 ) . Longitudinal associations of 20 fatty acids and three desaturase activities ( Δ5 ( 20:4n-6/20:3n-6 , D5D ) , Δ6 ( 18:3n-6/18:2n-6 , D6D ) , stearoyl-CoA desaturase-1 ( 16:1n-7/16:0 , SCD-1 ) ) with type 2 diabetes incidence , and estimates of insulin sensitivity ( Matsuda ) , secretion ( ratio of insulin and glucose concentrations ) and β-cell function ( disposition index ) by an oral glucose tolerance test were analyzed using Cox regression and linear mixed models . We vali date d estimated D5D and D6D using a known FADS1 gene variant , rs174550 . Results The baseline proportions of 20:5n-3 , 22:5n-3 and 22:6n-3 , and D5D were associated with lower incidence of type 2 diabetes during a median follow-up of 11 years ( HR per 1SD : 0.72 , 0.74 , 0.73 , 0.78 , respectively , P ≤ 0.01 ) . These long-chain omega-3 fatty acids and D5D were associated with higher insulin sensitivity in subsequent years but not with disposition index . Saturated , monounsaturated and trans fatty acids and 18:3n-3 , 18:2n-6 , SCD-1 and D6D were inconsistently associated with type 2 diabetes or related traits . Conclusions Serum long-chain omega-3 fatty acids and D5D predicted lower type 2 diabetes incidence in people at a high risk of diabetes attending to an intervention study ; a putative mechanism behind these associations was higher insulin sensitivity AIMS : The association between obesity and type 2 diabetes has been found to be consistent across different ethnic population s. Our aim was to study the contribution of obesity to the development of type 2 diabetes in a non-obese Chinese population with a high prevalence of diabetes ( 9.8 % in 1995–1996 ) . METHODS : Six-hundred and forty-four non-diabetic subjects were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study ( 1995–1996 ) . This was a community-based population study which involved the use of a 75 g oral glucose tolerance test and 1985 World Health Organization diagnostic criteria . Their glycemic status was reassessed at 2 y. RESULTS : In subjects with impaired glucose tolerance ( n=322 ) , the annual progression rate to diabetes ( 4.8 % ; 95 % CI 2.5–7.1 % ) , was 8-fold that in control subjects ( 0.6 % ; 95 % CI 0.0–1.4 % ; P<0.001 ) . Baseline waist – hip ratio ( WHR ; OR per unit increase=1.05 ; 95 % CI 1.02–1.07 , P=0.0003 ) and post-load 2 h plasma glucose ( OR per unit increase=2.02 ; 95 % CI 1.76–2.34 , P<0.0001 ) were significantly associated with glycemic status at 2 y in stepwise polytomous logistic regression analysis . Subjects with high baseline waist circumference or WHR ( ≥median ) were more likely to have worsening of glucose tolerance at 2 y than those with low waist circumference ( < median ; conversion to diabetes , OR 3.8 , P=0.001 ) or WHR ( < median ; conversion to diabetes , OR 2.8 , P=0.019 ) . CONCLUSION : Abdominal obesity , readily assessed by the measurement of WHR or waist circumference , was for the first time shown prospect ively to be independently associated with the deterioration of glucose tolerance in a Chinese population OBJECTIVE In adults , 1-h glucose during an oral glucose tolerance test ( OGTT ) predicts the development of type 2 diabetes independent of fasting and 2-h glucose concentrations . The purpose of the current investigation was to examine the utility of elevated 1-h glucose levels to prospect ively predict deterioration in β-cell function and the development of prediabetes in high-risk youth . RESEARCH DESIGN AND METHODS Obese Latino youth with a family history of type 2 diabetes ( 133 male and 100 female ; age 11.1 ± 1.7 years ) completed a baseline OGTT and were divided into two groups based upon a 1-h glucose threshold of 155 mg/dL ( < 155 mg/dL , n = 151 , or ≥155 mg/dL , n = 82 ) . Youth were followed annually for up to 8 years for assessment of glucose tolerance , body composition by dual-energy X-ray absorptiometry , and insulin sensitivity , insulin secretion , and the disposition index by the frequently sample d intravenous glucose tolerance test . RESULTS Over time , the ≥155 mg/dL group exhibited a significantly greater decline in β-cell function compared with youth with a 1-h glucose < 155 mg/dL ( β = −327.8 ± 126.2 , P = 0.01 ) . Moreover , this decline was independent of fasting or 2-h glucose and body composition . When the data were restricted to only participants with normal glucose tolerance at baseline , a 1-h glucose ≥155 mg/dL was independently associated with a 2.5 times greater likelihood of developing prediabetes during follow-up ( 95 % CI 1.6–4.1 , P = 0.0001 ) . CONCLUSIONS These data suggest that a 1-h glucose ≥155 mg/dL during an OGTT is an independent predictor of β-cell deterioration and progression to prediabetes among obese Latino youth OBJECTIVE To recalibrate and modify the Framingham diabetes mellitus ( DM ) function and establish a simple point score for predicting near-term incident diabetes in a large sample of Chinese . METHODS A total of 16,043 participants aged 50years or above without diabetes at baseline from the Guangzhou Biobank Cohort Study ( GBCS ) were recruited from 2003 to 2008 and followed up until 31 December 2012 , with an average follow-up period of 4.1years . A r and omly selected sub- sample of 8000 participants was used to calculate the predictive model and the remaining sample including 8043 participants was used for validating the prediction model . RESULTS During follow-up , 5.2 % ( 95 % confidence interval ( CI ) 4.6 - 5.9 ) of men and 5.2 % ( 95 % CI 4.8 - 5.6 ) of women developed diabetes . A GBCS point score prediction model was constructed based on the Framingham DM function risk factors using the r and omly selected sub- sample . Compared with the Framingham DM risk score ( AUC 0.740 , 95 % CI 0.715 - 0.766 ) , the GBCS point score prediction model predicted the development of diabetes well , with an AUC of 0.779 ( 95 % CI 0.756 - 0.801 , P for comparison < 0.001 ) . Validation analysis showed that the new GBCS function had satisfactory predictive ability for actual DM incidence and improved the calibration substantially . The original Framingham DM score underestimated diabetes incidence in the GBCS sample . CONCLUSIONS The constructed GBCS point score prediction model based on GBCS coefficients could be more useful for identifying high risk individuals in Chinese population s than the original Framingham DM score Background It is well known that anti-GAD ( glutamic acid decarboxylase ) serves as a marker for development of autoimmune diabetes in adults . On the other h and , the clinical implication s of anti-GAD positivity in persistently non-diabetic ( PND ) adults are poorly eluci date d. Our aim was to establish the frequency of anti-GAD in PNDs in an all- population -based cohort from the Nord-Trøndelag health study ( HUNT ) and to prospect ively test for associations with glucose tolerance and thyroid autoimmunity . Methods We formed a primary study population ( 4496 individuals ) , selected r and omly from the age group 20–90 years ( 50 % men/women ) , who were non-diabetic both at HUNT2 ( 1995–1997 ) and HUNT3 ( 2006–2008 ) . Anti-GAD-positive individuals at HUNT2 , together with anti-GAD-negative individuals aged 20–29 years , were retested for anti-GAD positivity at HUNT3 . A secondary study population consisted of individuals with type 2 diabetes ( T2D , n=349 ) at HUNT3 who developed diabetes between HUNT2 and HUNT3 . Results The frequency of anti-GAD positivity in PND was 1.7 % ( n=76 ) at HUNT2 . Positivity did not associate with gender , family history of diabetes , or glucose levels , but was associated with thyroid-associated autoimmunity ( increased frequency of positivity for anti-TPO ( thyroid peroxidase ) , p<0.002 ) . HLA-DQA1/DQB1 , a risk haplotype for autoimmunity , was also associated with anti-GAD positivity in PND . The incidence of anti-GAD positivity was low ( 0.4 % ) in the sub sample of individuals who were anti-GAD negative in HUNT2 . Anti-GAD positivity in PNDs was frequently evanescent , with 54 % losing , usually low- grade , positivity between HUNT2 and HUNT3 . An evanescent state of autoimmunity as assessed by anti-GAD positivity during “ pre-diabetes ” in individuals later diagnosed with T2D could , however , not be affirmed . Conclusions Anti-GAD positivity in PND is associated with HLA risk haplotypes and thyroid autoimmunity but not with clinical parameters of diabetes . Fleeting anti-GAD positivity is common ; however , results do not support the notion of a history of autoimmunity in T2D in the present cohort OBJECTIVE Various cutoff levels of hemoglobin A1c ( A1C ) have been suggested to screen for diabetes , although more consensus about the best level , especially for different ethnicities , is required . We evaluated the usefulness of A1C levels when screening for undiagnosed diabetes and as a predictor of 6-year incident diabetes in a prospect i ve , population -based cohort study . RESEARCH DESIGN AND METHODS A total 10,038 participants were recruited from the Ansung-Ansan cohort study . All subjects underwent a 75-g oral glucose tolerance test at baseline and at each biennial follow-up . Excluding subjects with a previous history of diabetes ( n = 572 ) , the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of the A1C cutoff . The Cox proportional hazards model was used to predict diabetes at 6 years . RESULTS At baseline , 635 participants ( 6.8 % ) had previously undiagnosed diabetes . An A1C cutoff of 5.9 % produced the highest sum of sensitivity ( 68 % ) and specificity ( 91 % ) . At 6 years , 895 ( 10.2 % ) subjects had developed incident diabetes . An A1C cutoff of 5.6 % had the highest sum of sensitivity ( 59 % ) and specificity ( 77 % ) for the identification of subsequent 6-year incident diabetes . After multivariate adjustment , men with baseline A1C ≥5.6 % had a 2.4-fold increased risk and women had a 3.1-fold increased risk of new-onset diabetes . CONCLUSIONS A1C is an effective and convenient method for diabetes screening . An A1C cutoff of 5.9 % may identify subjects with undiagnosed diabetes . Individuals with A1C ≥5.6 % have an increased risk for future diabetes AIMS Previous cross-sectional studies have established that South African Indians have a high prevalence of Type 2 diabetes mellitus . A prospect i ve community study was undertaken to determine the incidence of Type 2 diabetes and the risk factors associated with its development in a cohort of South African Indians who had been studied 10 years previously . METHODS This is a report on 563 subjects who participated both at baseline and at the 10-year follow-up study . In the baseline study , 2479 subjects ( > 15 years ) were studied ; using 1985 World Health Organization criteria for glucose tolerance based on 75 g oral glucose tolerance tests ( OGTT ) , the crude prevalence of diabetes mellitus ( Diabetes ) was 9.8 % and of impaired glucose tolerance ( IGT ) 5.8 % ( age and sex-adjusted prevalence 13 % and 6.9 % , respectively ) . RESULTS At the 10-year follow-up study , 563 of the subjects who could be traced consented to a repeat OGTT ; of these , 91 ( 16.2 % ) were classified as Diabetes and 41 ( 7.3 % ) as IGT . Of the subjects who did not have diabetes at baseline ( n = 517 ) , 49 ( 9.5 % ) progressed to diabetes ( PTD ) and 40 ( 7.7 % ) had IGT . The crude cumulative incidence of diabetes was 9.5 % ( rate of progression 0.95 % per annum ; incidence density 9.5/1000 person years ) with an age and sex-adjusted cumulative incidence of 8.3 % ( rate of progression 0.95 % per annum ; incidence density 8.3/1000 person years ) . Examination of risk factors predictive of subsequent diabetes development was undertaken by analysis of baseline ( year 0 ) variables in the 517 subjects who did not have diabetes at baseline . In multivariate analysis using a logistic regression model , the significant predictive risk factors for future diabetes included 2-h post load plasma glucose ( 2 PG ) ( P < 0.0001 , odds ratio ( OR ) 1.7 , 95 % confidence interval ( CI ) 1.4 - 2.1 ) , body mass index ( BMI ) ( P < 0.006 , OR 1.1 , 95 % CI 1.0 - 1.3 ) and obesity ( P < 0.01 , OR 4.6 , 95 % CI 1.4 - 14.7 ) . CONCLUSIONS This long-term study has shown that in South African Indians there is a high incidence of Type 2 diabetes , and in this population significant predictors include higher baseline blood glucose , BMI and obesity Aims /hypothesisThe value of diagnostic categories of glucose intolerance for predicting type 2 diabetes is much debated . We therefore sought to estimate relative and population -attributable risk of different definitions based on fasting ( impaired fasting glucose [ IFG ] ) or 2 h plasma glucose concentrations ( impaired glucose tolerance [ IGT ] ) and to describe the associated clinical phenotypes . Methods We prospect ively observed a population -based cohort of 1,963 non-diabetic participants ( mean age 47 years ) , in whom an OGTT was performed at baseline and 7 years later . Results IGT was fivefold more prevalent ( 13.5 % ) than IFG . In both categories , participants were older , heavier , hyperinsulinaemic , hyperproinsulinaemic and dyslipidaemic compared with participants with normal glucose tolerance . Relative risk of incident diabetes was similar for IFG and IGT categories ( 3.73 [ 95 % CI : 2.18–6.39 ] and 4.01 [ 95 % CI : 3.12–5.14 ] , respectively ) , but the population -attributable risk was fivefold higher for IGT ( 29 % [ 95 % CI : 26–32 ] ) than for IFG ( 6 % [ 95 % CI : 5–7 ] ) . Isolated IFG carried no increase in risk . Lowering the threshold to 5.6 mmol/l raised the population -attributable risk of IFG to 23 % ( 95 % CI : 20–25 ) ; its contribution to diabetes progression , however , was largely due to co-existent IGT . In multivariate analysis adjusting for sex , age , familial diabetes and BMI , fasting and 2 h glucose were independent predictors . Conclusions /interpretationFasting and 2 h glucose values are independent predictors of incident diabetes . Isolated IFG is not a high-risk condition ; lowering the diagnostic threshold increases the population -attributable risk of IFG fourfold , but performing an OGTT captures additional diabetes progressors compared with the number identified by IFG Background In an attempt to evaluate the levels of several cardiovascular risk factors in Greece we conducted a population -based health and nutrition survey , the " ATTICA study " . In this work we present the design and the methodology of the study , as well as the status of various baseline characteristics of the participants . Methods From May 2001 to December 2002 we r and omly enrolled 1514 adult men and 1528 adult women , stratified by age – gender ( census 2000 ) , from the greater area of Athens . More than 300 demographic , lifestyle , behavioral , dietary , clinical and biochemical variables have been recorded . Results Regarding the frequency of the classical cardiovascular risk factors we observed that 51 % of men and 39 % of women reported smokers ( p < 0.05 ) , 37 % of men and 25 % of women were defined as hypertensives ( p < 0.05 ) , 46 % of men and 40 % of women had total serum cholesterol levels above 200 mg/dl ( p < 0.05 ) and 8 % of men and 6 % of women had history of diabetes mellitus . Moreover , 20 % of men and 15 % of women were obese ( p < 0.05 ) , while men were more physically active as compared to women ( 42 % vs. 39 % , p < 0.05 ) . 19 % of men and 38 % of women had mild to severe depressive symptoms ( p < 0.01 ) . Finally , 72 men ( 5 % ) and 45 ( 3 % ) women reported history of coronary heart disease at entry evaluation . Conclusions The prevalence of the common cardiovascular risk factors in our population seems high . As a consequence a considerable proportion of Greek adults are at " high-risk " for future cardiovascular events Aims We prospect ively studied Japanese workers with impaired fasting glucose ( IFG ) and /or impaired glucose tolerance ( IGT ) and analysed possible risk factors for diabetes , including psychosocial factors such as stress . Methods The participants were 128 male Japanese company employees ( mean age , 49.3 ± 5.9 years ) with IFG and /or IGT diagnosed by oral glucose tolerance test ( OGTT ) . Participants were prospect ively studied for 5 years with annual OGTTs . The Kaplan – Meier method and Cox 's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance , including anthropometric , biochemical and social – psychological factors . Results Of 128 participants , 36 ( 28.1 % ) developed diabetes and 39 ( 30.5 % ) returned to normal glucose tolerance ( NGT ) during a mean follow-up of 3.2 years . Independent risk factors for diabetes were night duty [ hazard ratio ( HR ) = 5.48 , P = 0.002 ] , higher fasting plasma glucose ( FPG ) levels within 6.1–6.9 mmol/l ( HR = 1.05 , P = 0.031 ) , stress ( HR = 3.81 , P = 0.037 ) and administrative position ( HR = 12.70 , P = 0.045 ) , while independent factors associated with recovery were lower FPG levels ( HR = 0.94 , P = 0.017 ) , being a white-collar worker ( HR = 0.34 , P = 0.033 ) , non-smoking ( HR = 0.31 , P = 0.040 ) and lower serum alanine aminotransferase ( ALT ) levels ( HR = 0.97 , P = 0.042 ) . Conclusions In addition to FPG levels at baseline , psychosocial factors ( night duty , stress and administrative position ) are risk factors for Type 2 diabetes , while being a white-collar worker , a non-smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and /or IGT OBJECTIVE A1C has been proposed as a new indicator for high risk of type 2 diabetes . The long-term predictive power and comparability of elevated A1C with the currently used high-risk indicators remain unclear . We assessed A1C , impaired glucose tolerance ( IGT ) , and impaired fasting glucose ( IFG ) as predictors of type 2 diabetes and cardiovascular disease ( CVD ) at 10 years . RESEARCH DESIGN AND METHODS This prospect i ve population -based study of 593 inhabitants from northern Finl and , born in 1935 , was conducted between 1996 and 2008 . An oral glucose tolerance test ( OGTT ) was conducted at baseline and follow-up , and A1C was determined at baseline . Those with a history of diabetes were excluded from the study . Elevated A1C was defined as 5.7–6.4 % . Incident type 2 diabetes was confirmed by two OGTTs . Cardiovascular outcome was measured as incident CVD or CVD mortality . Multivariate log-binomial regression models were used to predict diabetes , CVD , and CVD mortality at 10 years . Receiver operating characteristic curves compared predictive values of A1C , IGT , and IFG . RESULTS Incidence of diabetes during the follow-up was 17.1 % . Two of three of the cases of newly diagnosed diabetes were predicted by a raise in ≥1 of the markers . Elevated A1C , IGT , or IFG preceded diabetes in 32.8 , 40.6 , and 21.9 % , respectively . CVD was predicted by an intermediate and diabetic range of 2-h glucose but only by diabetic A1C levels in women . CONCLUSIONS A1C predicted 10-year risk of type 2 diabetes at a range of A1C 5.7–6.4 % but CVD only in women at A1C ≥6.5 % OBJECTIVE To study the prevalence , awareness and control of hypertension in Chennai representing Urban South India . METHODS The Chennai Urban Rural Epidemiology Study ( CURES ) is one of the largest epidemiological studies on diabetes carried out in India , where 26,001 individuals aged > or = 20 years were screened using systematic r and om sampling method . Every tenth subject recruited in Phase 1 of CURES was requested to participate in Phase 3 of CURES and the response rate was 2,350/26,001 or 90.4 % . An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects . Anthropometric measurements and lipid estimations were done in all subjects . Hypertension was diagnosed in all subjects who were on drug treatment for hypertension or if the blood pressure > or = 140/90 mmHg . RESULTS Hypertension was present in 20 % [ men:23.2 % vs. women:17.1 % , p<0.001 ] of the study population . Isolated systolic hypertension ( Systolic BP > or = 140 and Diastolic BP<90 mmHg ) was present in 6.6 % while isolated diastolic hypertension ( DBP > or = 90 and SBP<140 mmHg ) was present in 4.2 % of the population . Among the elderly population ( aged > or = 60 years ) , 25.2 % had isolated systolic hypertension . Age , body mass index , smoking , serum cholesterol and triglycerides were found to be strongly associated with hypertension . Among the total hypertensive subjects , only 32.8 % were aware of their blood pressure , of these , 70.8 % were under treatment and 45.9 % had their blood pressure under control . CONCLUSION Hypertension was present in one-fifth of this urban south Indian population and isolated systolic hypertension was more common among elderly population . Majority of hypertensive subjects still remain undetected and the control of hypertension is also inadequate . This calls for urgent prevention and control measures for hypertension Abstract The worldwide prevalence and incidence of diabetes and obesity are increasing in p and emic proportions . This is particularly relevant for China , where an extremely large population is growing , aging , and urbanizing . We thus conducted a prospect i ve study to examine the prevalence and incidence of impaired fasting glucose ( IFG ) and diabetes , the rate at which fasting blood glucose rises , and the major modifiable risk factors associated with these outcomes in a large Chinese population from the Kailuan prospect i ve study .A prospect i ve cohort included 100,279 Chinese participants , aged 18 years or more , who had available information on fasting blood glucose concentrations at the start of the study ( 2006 ) . Examination surveys were conducted every 2 years in 2008 and 2010 . For the analyses of incident diabetes , we included 76,869 participants who were free of diabetes , cardiovascular disease , and cancer at the baseline and participants in the 2008 and /or 2010 follow-up . Diabetes was defined by a fasting blood glucose concentration ≥7 mmol/L , self-reported history , or active treatment with insulin or any oral hypoglycemic agent . IFG was defined by a fasting blood glucose concentration between 5.6 and 6.9 mmol/L.During the 4-year study , the prevalence of diabetes and IFG rose from 6.6 % to 7.7 % , and 17.3 % to 22.6 % , respectively . There were 17,811 incident cases of IFG and 4867 incident cases of diabetes . The age-st and ardized incident rate of IFG and diabetes were 62.6/1000 person-years ( 51.2/1000 person-years in women and 73.8/1000 person-years in men ) and 10.0/1000 person-years ( 7.8/1000 person-years in women and 12.1/1000 person-years in men ) , respectively . We observed steady increases in fasting blood glucose with body anthropometrics and in every defined category of body mass index , including in those traditionally considered to be well within the “ normal ” range . In this large longitudinal study of Chinese adults , we observed a high prevalence and incidence of IFG and diabetes over 4 years of follow-up . Our findings are alarming for Chinese public health since steady rises in fasting blood glucose were seen across all permutations of body habitus , even apparently very lean individuals Abstract Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category . In this study , we aim ed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0 , 30 , 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospect i ve community-based cohort in Korea . Among subjects enrolled at the Chungju Metabolic disease Cohort , those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline . Subjects were categorized according to their 30 minute glucose ( G30 ) and the difference between 120 and 0 minute glucose ( G(120–0 ) ) levels with cutoffs of 9.75 and 2.50 mmol/L , respectively . Among 1126 subjects , 117 ( 10.39 % ) developed type 2 diabetes after 4 years . In diabetes nonconverters , increased insulin resistance was accompanied by compensatory insulin secretion , but this was not observed in converters during 4 years of follow-up . Subjects with G(120–0 ) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion , higher degrees of insulin resistance , and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors . Moreover , subjects with high G(120–0 ) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120–0 ) and low G30.By using the G(120–0 ) and G30 values obtained during the OGTT , which are less complicated measurements than previously reported methods , we were able to select individuals at risk for future diabetes development . Further studies in different ethnicities are required to vali date our results OBJECTIVE To determine the population -based prevalence of diabetes and other categories of glucose intolerance ( impaired glucose tolerance [ IGT ] and impaired fasting glucose [ IFG ] ) in Australia and to compare the prevalence with previous Australian data . RESEARCH DESIGN AND METHODS A national sample involving 11,247 participants aged > or = 25 years living in 42 r and omly selected areas from the six states and the Northern Territory were examined in a cross-sectional survey using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma glucose concentrations . The World Health Organization diagnostic criteria were used to determine the prevalence of abnormal glucose tolerance . RESULTS The prevalence of diabetes in Australia was 8.0 % in men and 6.8 % in women , and an additional 17.4 % of men and 15.4 % of women had IGT or IFG . Even in the youngest age group ( 25 - 34 years ) , 5.7 % of subjects had abnormal glucose tolerance . The overall diabetes prevalence in Australia was 7.4 % , and an additional 16.4 % had IGT or IFG . Diabetes prevalence has more than doubled since 1981 , and this is only partially explained by changes in age profile and obesity . CONCLUSIONS Australia has a rapidly rising prevalence of diabetes and other categories of abnormal glucose tolerance . The prevalence of abnormal glucose tolerance in Australia is one of the highest yet reported from a developed nation with a predominantly Europid background OBJECTIVE To determine A1C cut points for glucose intolerance in Asian Indians . RESEARCH DESIGN AND METHODS A total of 2,188 participants without known diabetes were r and omly selected from the Chennai Urban Rural Epidemiology Study . All had fasting plasma glucose ( FPG ) and 2-h postload plasma glucose measurements after a 75-g load and were classified as having impaired fasting glucose ( IFG ) ( American Diabetes Association [ ADA ] criteria , FPG ≥5.5 and < 7 mmol/l , and World Health Organization [ WHO ] criteria , FPG ≥6.1 and < 7 mmol/l ) , impaired glucose tolerance ( IGT ) ( 2-h postload plasma glucose ≥7.8 and < 11.1 mmol/l ) , or diabetes ( FPG ≥7 mmol/l and /or 2-h postload plasma glucose ≥11.1 mmol/l ) . A1C was measured using the Bio-Rad Variant machine . Based on receiver operating characteristic curves , optimum sensitivity and specificity were derived for defining A1C cut points for diabetes , IGT , and IFG . RESULTS Mean ± SD values of A1C among subjects with normal glucose tolerance , IGT , and diabetes were 5.5 ± 0.4 , 5.9 ± 0.6 , and 8.3 ± 2.0 % , respectively ( Ptrend < 0.001 ) with considerable overlap . To identify diabetes based on 2-h postload plasma glucose , the A1C cut point of 6.1 % had an area under the curve ( AUC ) of 0.941 with 88.0 % sensitivity and 87.9 % specificity . When diabetes was defined as FPG ≥7.0 mmol/l , the A1C cut point was 6.4 % ( AUC = 0.966 , sensitivity 93.3 % , and specificity 92.3 % ) . For IGT , AUC = 0.708 ; for IFG , AUC = 0.632 ( WHO criteria ) and 0.708 ( ADA criteria ) , and the A1C cut point was 5.6 % . CONCLUSIONS In Asian Indians , A1C cut points of 6.1 and 6.4 % defined diabetes by 2-h postload plasma glucose or FPG criteria , respectively . A value of 5.6 % optimally identified IGT or IFG but was < 70 % accurate OBJECTIVE To develop and evaluate clinical rules to predict risk for diabetes in middle-aged adults . RESEARCH DESIGN AND METHODS The Atherosclerosis Risk in Communities is a cohort study conducted from 1987 - 1989 to 1996 - 1998 . We studied 7,915 participants 45 - 64 years of age , free of diabetes at baseline , and ascertained 1,292 incident cases of diabetes by clinical diagnosis or oral glucose tolerance testing . RESULTS We derived risk functions to predict diabetes using logistic regression in a r and om half of the sample . Rules based on these risk functions were evaluated in the other half . A risk function based on waist , height , hypertension , blood pressure , family history of diabetes , ethnicity , and age was performed similarly to one based on fasting glucose ( area under the receiver-operating characteristic curve [ AUC ] 0.71 and 0.74 , respectively ; P = 0.2 ) . Risk functions composed of the clinical variables plus fasting glucose ( AUC 0.78 ) and additionally including triglycerides and HDL cholesterol ( AUC 0.80 ) performed better ( P < 0.001 ) . Evaluation of scores based on the metabolic syndrome as defined by the National Cholesterol Education Program or with slight variations showed AUCs of 0.75 and 0.78 , respectively . Rules based on all these approaches , while identifying 20 - 56 % of the sample as screen positive , achieved sensitivities of 40 - 87 % and specificities of 50 - 86 % . CONCLUSIONS Rules derived from clinical information , alone or combined with simple laboratory measures , can characterize degrees of diabetes risk in middle-aged adults , permitting preventive actions of appropriate intensity . Rules based on the metabolic syndrome are reasonable alternatives to rules derived from risk functions The report of World Health Organization ( WHO ) shows that India tops the world with the largest number of diabetic subjects . This increase is attributed to the rapid epidemiological transition accompanied by urbanization , which is occurring in India . There is very little data regarding the influence of affluence on the prevalence of diabetes and its complications particularly retinopathy in the Indian population . Furthermore , there are very few studies comparing the urban/rural prevalence of diabetes and its complications . The Chennai Urban Rural Epidemiology Study ( CURES ) is design ed to answer the above questions . CURES is initially planned as a cross-sectional study to evolve later into a longitudinal study . Subjects for the urban component of the CURES have been recruited from within the corporation limits of Chennai City . Chennai ( formerly Madras ) , the largest city in Southern India and the fourth largest in India has been divided into 10 zones and 155 wards . 46 wards were selected by a systematic r and om sampling method to represent the whole of Chennai . Twenty thous and and one individuals were recruited for the study , this number being derived based on a sample size calculation . The study has three phases . Phase one is a door to door survey which includes a question naire , anthropometric , fasting capillary blood glucose and blood pressure measurements . Phase two focussed on the prevalence of diabetic complications particularly retinopathy using st and ardized techniques like retinal photography etc . Diabetic subjects identified in phase one and age and sex matched non-diabetic subjects will participate in these studies . Phase three will include more detailed studies like clinical , biochemical and vascular studies on a sub- sample of the study subjects selected on a stratified basis from phase one . CURES is perhaps one of the largest systematic population based studies to be done in India in the field of diabetes and its complications like retinopathy , nephropathy and neuropathy OBJECTIVE To determine the effect of lowering the fasting plasma glucose ( FPG ) criterion for impaired fasting glucose ( IFG ) on the prevalence of IFG , the risks of diabetes , and cardiovascular disease ( CVD ) associated with IFG . RESEARCH DESIGN AND METHODS Three studies were used : 1 ) . the 1998 National Health Survey ( NHS98 ) , a r and omly selected cross-sectional sample of 4723 subjects ; 2 ) . the Singapore Impaired Glucose Tolerance ( IGT ) Follow-up Study , a cohort study comprising 295 IGT and 292 normal glucose tolerance subjects ( frequency matched for age , sex , and ethnic group ) followed up from 1992 to 2000 ; and 3 ) . the Singapore CVD Cohort Study , comprising 5920 subjects from three cross-sectional studies in whom the first ischemic heart disease ( IHD ) event was identified through linkage to registry data bases . Risk of diabetes ( Singapore IGT Follow-up study ) was estimated using logistic regression adjusted for age , sex , and ethnicity . Risk of IHD ( Singapore CVD cohort ) was estimated using stratified ( by study , from which data were derived ) Cox 's proportional hazards models adjusted for age , sex , and ethnicity . RESULTS Lowering the criterion for diagnosing IFG to 5.6 mmol/l increased the prevalence of IFG from 9.5 to 32.3 % in the NHS98 . The lower cutoff identified more subjects at risk of diabetes and IHD , but the relative risk was lower than that for IGT . CONCLUSIONS Greater efforts to identify those with IGT , or a group at similar risk of diabetes and CVD , may be a more efficient public health measure than lowering the FPG criterion for diagnosing IFG This is the last in a series of four articles Prognostic studies include clinical studies of variables predictive of future events as well as epidemiological studies of aetiological risk factors . As multiple similar studies accumulate it becomes increasingly important to identify and evaluate all of the relevant studies to develop a more reliable overall assessment . For prognostic studies this is not straightforward . Box 1 summarises the clinical importance of information on prognostic factors . Many of the issues discussed are also relevant to aetiological studies , especially cohort ones . Some features of prognostic studies lead to particular difficulties for the systematic review er . Firstly , in most clinical prognostic studies the outcome of primary interest is the time to an event , often death . Meta- analysis of such studies is rather more difficult than that for binary data or continuous measurements . Secondly , in many context s the prognostic variable of interest is often one of several prognostic variables . When examining a variable of interest research ers should consider other prognostic variables with which it might be correlated . Thirdly , many prognostic factors are continuous variables , for which research ers use a wide variety of methods of analysis . # # # # Summary points Systematic review s are applicable to all types of research design , and studies of prognostic variables are an important additional area where appropriate methodology should be applied Prognostic variables should be evaluated in a representative sample of patients assembled at a common point in the course of their disease — ideally they should all have received the same medical treatment or been in a r and omised trial When examined critically , a high proportion of prognostic studies are found to be method ologically poor Meta- analysis of published data is hampered by difficulties in extraction of data and variation in the characteristics of the study and patients The poor quality of the published literature is a strong argument in favour OBJECTIVE —Early identification of subjects at high risk for diabetes is essential , and r and om HbA1c ( A1C ) may be more practical than fasting plasma glucose ( FPG ) . The predictive value of A1C , in comparison to FPG , is evaluated for 6-year incident diabetes . RESEARCH DESIGN AND METHODS —From the French cohort study Data from an Epidemiological Study on the Insulin Resistance Syndrome ( DESIR ) , 1,383 men and 1,437 women , aged 30–65 years , were volunteers for a routine health check-up . Incident diabetes was defined by FPG ≥7.0 mmol/l or treatment by antidiabetic drugs . Multivariate logistic regression models were used to predict diabetes at 6 years . Receiver operating characteristic curves compared the predictive values of A1C and FPG . RESULTS —At 6 years , 30 women ( 2.1 % ) and 60 men ( 4.3 % ) had developed diabetes . Diabetes risk increased exponentially with A1C in both sexes ( P < 0.001 ) . After stratifying on FPG , A1C predicted diabetes only in subjects with impaired fasting glucose ( IFG ) ( FPG ≥6.10 mmol/l ) : the odds ratio ( 95 % CI ) for a 1 % increase in A1C was 7.20 ( 3.00–17.00 ) . In these subjects , an A1C of 5.9 % gave an optimal sensitivity of 64 % and specificity of 77 % to predict diabetes . CONCLUSIONS —A1C predicted diabetes , even though the diagnosis of diabetes was based on FPG , but it was less sensitive and specific than FPG . It could be used as a test if fasting blood sampling was not available or in association with FPG . In subjects with IFG , A1C is better than glucose to evaluate diabetes risk , and it could be used to select subjects for intensive early intervention The criteria of the American Diabetes Association and the WHO for the diagnosis of diabetes mellitus are controversially discussed . In a prospect i ve population study , we evaluated the data of 3,737 men , aged 36 - 60 yr , without diabetes mellitus and with fasting serum glucose levels less than 7 mmol/L at entry into the study who had at least 1 repeat examination during a follow-up of 4 - 10 yr . During a mean follow-up of 6.3 yr , 200 men developed diabetes mellitus . They differed significantly from 3,537 men by body mass index , fasting serum levels of glucose , high density lipoprotein cholesterol , and family history positive for diabetes mellitus . Receiver operating curve analysis revealed that a glucose level of 5.72 mmol/L was the best discriminatory cut-off . Upon global risk estimation by multiple logistic function ( MLF ) analysis , 69.6 % of all diabetes mellitus incidences occurred in the highest quintile as defined by the MLF algorithm . The relative risk of a men in this quintile was 8.7 compared to that in the residual population . The performance of risk assessment by MLF as estimated by the area under the receiver operator characteristic curve was similar to fasting glucose levels . Global risk estimation by multiple risk factors does not improve the prediction of diabetes mellitus by fasting glucose in middle-aged men . The lower discriminatory cut-off of 5.72 mmol/L glucose may help to reduce the previously reported discordance between impaired fasting glucose ( American Diabetes Association ) and impaired glucose tolerance ( WHO ) in diagnosis of the prediabetic state Background : Positive predictive value ( PPV ) of hemoglobin A1c ( HbA1c ) for diagnosis of prediabetes in clinical practice has not been well studied . Methods : In a prospect i ve study , patients diagnosed with prediabetes based on HbA1c ( 5.7%–6.4 % ) underwent a 75-g oral glucose tolerance test ( OGTT ) as the gold st and ard test to diagnose dysglycemia . Demographics , anthropometrics , comorbidity , concomitant prescription medications and biochemical data were collected . Results : We identified 66 patients with HbA1c-based prediabetes with a mean HbA1c of 6.00 ± 0.20 % . However , based on the OGTT , 32 had normal glucose tolerance ( NGT ) , 26 had prediabetes and 8 had diabetes yielding a PPV of HbA1c of 39.4 % . In univariate analysis , the patients with the OGTT-based prediabetes administered more medications for associated medical problems compared with the NGT group ( 5.9 ± 2.2 versus 2.6 ± 1.8 , P < 0.0001 ) . After adjustment for baseline variables , the medication use remained significantly different between OGTT-based prediabetes and NGT groups ( P = 0.041 ) . Conclusions : PPV of HbA1c for diagnosis of prediabetes in clinical setting is low . Patients with HbA1c of 5.7 % to 6.4 % should undergo OGTT to confirm diagnosis of dysglycemia The San Luis Valley Diabetes Study was undertaken to determine the prevalence , risk factors , and complications of non-insulin-dependent diabetes mellitus in Hispanics and Anglos ( non-Hispanic whites ) , using a geographically based case-control design . The study was conducted in two southern Colorado counties that include 43.6 % Hispanic and 54.9 % Anglo persons . Medical practice records were review ed to identify medically diagnosed diabetics . Controls without diabetes were identified by a two-stage r and om sample of households . Diabetics ( n = 343 ) and controls ( n = 607 ) attended a clinic where an oral glucose tolerance test or current hypoglycemic therapy confirmed or diagnosed non-insulin-dependent diabetes mellitus . The age-adjusted prevalence of confirmed non-insulin-dependent diabetes mellitus was 21/1,000 in Anglo males and 44/1,000 in Hispanic males , accounting for non-response . For Anglo females , the prevalence was 13/1,000 compared with 62/1,000 for Hispanic females , accounting for nonresponse . Previously undiagnosed non-insulin-dependent diabetes mellitus was also higher among Hispanics . There was a 2.1-fold excess of confirmed non-insulin-dependent diabetes mellitus among Hispanic males and a 4.8-fold excess among Hispanic females , consistent with the excess non-insulin-dependent diabetes mellitus among Hispanics reported from comparable studies . Non-insulin-dependent diabetes mellitus is a major chronic disease problem for persons of Hispanic ethnicity Objective We wanted to determine whether obesity , abdominal fat distribution , and physical inactivity act similarly and independently as risk factors for noninsulin- dependent diabetes mellitus ( NIDDM ) and impaired glucose tolerance ( IGT ) in Hindu and Muslim Asian Indians , African-origin Creoles , and Chinese Mauritians . Research Design and Methods We examined a population -based r and om cluster sample of 5080 adult subjects from the Indian Ocean isl and of Mauritius . Glucose tolerance was assessed with a 75-g oral glucose tolerance test and World Health Organization criteria . Results Univariate data and multiple logistic regression models indicated that age , family history of diabetes , body mass index ( BMI ) , waisthip ratio ( WHR ) , and physical inactivity conveyed similar risk for NIDDM ( and IGT ) in each ethnic group . After adjusting for all other factors , Hindu ethnicity conferred additional risk for NIDDM ( but not IGT ) in men , but in women there were no clear ethnic differences . Although BMI and WHR were independently significant risk factors , WHR conveyed relatively stronger risk for NIDDM than BMI in women , whereas the converse was true in men . For ethnic groups combined , the independent odds ratios for IGT associated with moderate and low physical activity scores ( relative to high ) were 1.56 and 1.71 ( P < 0.05 ) , respectively , in men and 1.32 and 1.69 ( P < 0.05 ) in women . In subjects with asymptomatic NIDDM diagnosed during the survey , the independent odds ratios were 1.96 and 2.00 ( P < 0.05 ) in men and 1.73 and 2.70 ( P < 0.05 ) in women . Conclusions These data indicate that BMI , abdominally distributed fat , and physical inactivity are important independent risk factors for both IGT and NIDDM in diverse ethnic groups . Attributable risk fractions for Mauritius suggest that population wide modification of levels of these risk factors could potentially result in substantially lower occurrence of NIDDM ( and IGT ) . Such interventions should be attempted in high-risk population OBJECTIVE To determine the prevalence of diabetes and impaired glucose tolerance ( IGT ) in Yonchon County of South Korea and to investigate their associated factors . RESEARCH DESIGN AND METHODS We performed a population -based cross-sectional study with r and om cluster sampling of residents ≥30 years of age . Among the 3,804 residents sample d , a total of 2,520 participants had a st and ard 75-g oral glucose tolerance test and answered a detailed question naire . We also collected st and ard anthropometric data . RESULTS If the data for participants in the age range of 30–64 years were adjusted to the st and ard world population , the prevalence of diabetes was 7.2 % and the prevalence of IGT was 8.9 % . It was observed that the significant factors associated with diabetes were waist-to-hip circumference ratio , serum triglyceride levels , age , systolic blood pressure , family history of diabetes , and locality . CONCLUSIONS The prevalence of diabetes in Yonchon County was substantially higher than was previously suggested . The risk of diabetes increased with the increased central obesity and metabolic disturbances associated with insulin resistance Background and objective : In Sweden , mortality from cardiovascular diseases ( CVD ) increased steadily during the 20th century and in the mid-1980s it was highest in the county of Västerbotten . Therefore , a community intervention programme was launched – the Västerbotten Intervention Programme ( VIP ) – with the aim of reducing morbidity and mortality from CVD and diabetes . Design : The VIP was first developed in the small municipality of Norsjö in 1985 . Subsequently , it was successively implemented across the county and is now integrated into ordinary primary care routines . A population -based strategy directed towards the public is combined with a strategy to reach all middle-aged persons individually at ages 40 , 50 and 60 years , by inviting them to participate in systematic risk factor screening and individual counselling about healthy lifestyle habits . Blood sample s for research purpose s are stored at the Umeå University Medical Biobank . Results : Overall , 113,203 health examinations have been conducted in the VIP and 6,500–7,000 examinations take place each year . Almost 27,000 subjects have participated twice . Participation rates have ranged between 48 and 67 % . A dropout rate analysis in 1998 indicated only a small social selection bias . Cross-sectional , nested case-control studies and prospect i ve studies have been based on the VIP data . Linkages between the VIP and local , regional and national data bases provide opportunities for interdisciplinary research , as well as national and international collaborations on a wide range of disease outcomes . A large number of publications are based on data that are collected in the VIP , many of which also use results from analysed stored blood sample s. More than 20 PhD theses have been based primarily on the VIP data . Conclusions : The concept of the VIP , established as a collaboration between politicians and health care providers on the one h and and primary care , functioning as the operating machinery , and the public on the other , forms the basis for effective implementation and endurance over time . After more than 20 years of the VIP , there is a large comprehensive population -based data base , a stable organisation to conduct health surveys and collect data , and a solid structure to enable widespread multidisciplinary and scientific collaborations Summary This report presents data on antecedents of Type 2 ( non-insulin-dependent ) diabetes mellitus in a homogeneous sample of r and omly selected 54-year-old men from an urban Swedish population with a diabetes incidence of 6.1 % during 13.5 years of follow-up . The increased risk leading to diabetes for those in the top quintile compared to the lowest quintile of the distribution of statistically significant risk factors were : body mass index = 21.7 , triglycerides = 13.5 , waist-to-hip circumference ratio = 9.6 , diastolic blood pressure = 6.7 , uric acid = 5.8 , glutamic pyruvic transaminase = 3.9 , bilirubin = 3.2 , blood glucose = 2.7 , lactate = 2.4 and glutamic oxaloacetic transaminase = 2.0 . Those with a positive family history of diabetes had 2.4-fold higher risk for developing diabetes than those without such a history . In a multivariate analysis glutamic pyruvic transaminase , blood glucose , body mass index , bilirubin , systolic blood pressure , uric acid and a family history of diabetes were all significantly associated with the development of diabetes . Our study demonstrates the great importance of adiposity and body fat distribution for the risk of diabetes . A number of established risk factors for coronary heart disease are risk factors for diabetes as well . Disturbed liver function and increased levels of lactate are early risk factors for diabetes — presumably indicators of the presence of impaired glucose tolerance and /or hyperinsulinaemia Abstract Objective : To determine the risk factors for non-insulin dependent diabetes in a cohort representative of middle aged British men . Design : Prospect i ve study . Subjects and setting : 7735 men aged 40 - 59 , drawn from one group practice in each of 24 towns in Britain . Known and probable cases of diabetes at screening ( n=158 ) were excluded . Main outcome measures : Non-insulin dependent diabetes ( doctor diagnosed ) over a mean follow up period of 12.8 years . Results : There were 194 new cases of non-insulin dependent diabetes . Body mass index was the dominant risk factor for diabetes , with an age adjusted relative risk ( upper fifth to lower fifth ) of 11.6 ; 95 % confidence interval 5.4 to 16.8 . Men engaged in moderate levels of physical activity had a substantially reduced risk of diabetes , relative to the physically inactive men , after adjustment for age and body mass index ( 0.4 ; 0.2 to 0.7 ) , an association which persisted in full multivariate analysis . A non-linear relation between alcohol intake and diabetes was observed , with the lowest risk among moderate drinkers ( 16 - 42 units/week ) relative to the baseline group of occasional drinkers ( 0.6 ; 0.4 to 1.0 ) . Additional significant predictors of diabetes in multivariate analysis included serum triglyceride concentration , high density lipoprotein cholesterol concentration ( inverse association ) , heart rate , uric acid concentration , and prevalent coronary heart disease . Conclusion : These findings emphasise the interrelations between risk factors for non-insulin dependent diabetes and coronary heart disease and the potential value of an integrated approach to the prevention of these conditions based on the prevention of obesity and the promotion of physical activity . Key messages Key messages This study shows a strong , grade d association between body mass index and risk of diabetes in middle aged men , with no evidence of a threshold effect The risk of diabetes is reduced by more than 50 % among men who take moderately vigorous exercise Cardiovascular disease risk factors that are linked with insulin resistance , such as hypertriglyceridaemia and hyperuricaemia , predict non-insulin dependent diabetes These findings support an integrated approach to the prevention of non-insulin dependent diabetes and cardiovascular disease based on the prevention of obesity and the promotion of physical CONTEXT Glycated hemoglobin ( A1C ) has been recommended by the American Diabetes Association for the diagnosis of diabetes and prediabetes . The diagnostic utility of A1C has not been evaluated in Arabs , a population at increased risk for developing diabetes . OBJECTIVE Our objective was to examine the sensitivity and specificity of A1C for the diagnosis of diabetes and prediabetes in Arabs . DESIGN & SETTING In this cross-sectional study , glucose tolerance was classified by the American Diabetes Association diagnostic criteria specified for A1C , fasting plasma glucose , and 75-g oral glucose tolerance test . PARTICIPANTS A population -based representative sample of 482 r and omly selected adult Arabs without known diabetes was studied . MAIN OUTCOME MEASURES Sensitivity , specificity , and area under the receiver operating characteristic curve of A1C diagnostic cutpoints for diabetes and prediabetes were calculated . κ Coefficients were used to test for agreement between A1C categorization and glucose-based diagnoses . RESULTS A1C testing correctly identified 5 % of individuals diagnosed with diabetes by oral glucose tolerance test , 13 % by fasting plasma glucose , and 41 % by both criteria . A1C alone identified 14 % of individuals diagnosed with impaired glucose tolerance , 9 % with impaired fasting glucose , and 33 % with both abnormalities . Sensitivity , specificity , and area under the receiver operating characteristic curve were 19 % ( 16 - 23 % ) , 100 % ( 99 - 100 % ) , and 77 % ( 69 - 85 % ) for diabetes A1C cutpoint and 14 % ( 11 - 17 % ) , 91 % ( 89 - 94 % ) , and 57 % ( 52 - 62 % ) for prediabetes A1C range . A1C cutpoint of 6.2 % for diabetes and 5.1 % for prediabetes yielded the highest accuracy but still missed 73 % of those with diabetes and 31 % with prediabetes . Agreement between A1C and diabetes ( κ = 0.2835 ) or prediabetes ( κ = 0.0530 ) was low . CONCLUSIONS A1C-based criteria yield a high proportion of false-negative tests for diabetes and prediabetes in Arabs . SUMMARY Racial/ethnic differences in A1C performance for diagnosis and prediction of diabetes exist . This paper examines its utility against glucose measurements in an at-risk Arab population AIM Fasting plasma glucose ( FPG ) and the 2-h post-challenge plasma glucose ( 2hPG ) are commonly used to identify those at risk of type 2 diabetes . However , the role of HbA(1c ) in this prediction has still not been ascertained . METHODS The Asturias study is a prospect i ve population -based survey of diabetes and cardiovascular risk factors . Baseline examination , carried out during 1998 - 1999 , involved 1034 individuals , aged 30 - 75 years , r and omly selected to determine the prevalence of type 2 diabetes and prediabetes in the principality of Asturias ( northern Spain ) . In 2004 - 2005 , these same subjects were invited to a follow-up examination , and 700 participated . The present study includes only those who did not have diabetes at baseline . All participants with no known diabetes underwent an OGTT . Baseline HbA(1c ) levels were measured by HPLC . RESULTS Diabetes had developed in 44 participants at the time of follow-up . Quartiles of baseline HbA(1c ) values were 3.4 - 4.8 ( Q1 ) , 4.9 - 5.1 ( Q2 ) , 5.2 - 5.4 ( Q3 ) and 5.5 - 6.9 ( Q4 ) , and the incidence rates of diabetes by quartiles were 1.0 ( 0.1 - 7.1 ) , 4.0 ( 1.5 - 10.7 ) , 7.9 ( 4.0 - 15.9 ) and 32.6 ( 22.9 - 46.4 ) cases/1000 person-years , respectively . ROC curve analysis comparing HbA(1c ) , FPG and 2hPG in the prediction of diabetes showed areas under the curve ( ROC-AUC ) of 0.80 ( 0.74 - 0.86 ) , 0.83 ( 0.77 - 0.90 ) and 0.79 ( 0.72 - 0.87 ) , respectively . The combination of FPG and HbA(1c ) had the best predictive performance with an ROC-AUC of 0.88 ( 0.82 - 0.93 ) . CONCLUSION Our study indicates that HbA(1c ) is strongly predictive of new-onset diabetes in this northern Spanish population , and was similar to FPG and 2hPG in predictive capability . Also , the combined measurement of FPG and HbA(1c ) improved their individual predictive performance AIMS Impaired glucose tolerance ( IGT ) is regarded at risk factor for later diabetes . The aim of this study was to identify predictive factors for outcome of IGT in obese children and adolescents . METHODS We prospect ively examined 79 obese white children and adolescents ( mean age 13.1 + /- 2.1 years , 51 % female , 76 % pubertal ) with IGT . Anthropometrics , 2-h glucose in oral glucose tolerance test ( OGTT ) , fasting glucose , insulin , insulin resistance index homeostasis model assessment ( HOMA ) , glycated haemoglobin ( HbA(1c ) ) , lipids , blood pressure , waist circumference and pubertal stage were determined at baseline and 1 year later . RESULTS At follow-up , 32 % of the children continued to have IGT , 66 % converted to normal glucose metabolism , one child had impaired fasting glucose and one child developed Type 2 diabetes mellitus ( T2DM ) . Children with improvement of IGT had significantly lower weight , waist circumference , triglycerides , 2-h glucose during OGTT and HbA(1c ) at baseline compared with children who continued to have IGT . In the children whose glucose tolerance became normal , weight fell , and serum insulin concentrations , HOMA , lipids and blood pressure improved . They were also more likely to enter the late or post-pubertal stage than children who continued to have IGT . CONCLUSIONS Predictive factors for the frequent normalization of IGT in obese children and adolescents were lower weight , HbA(1c ) and 2-h glucose levels in OGTT at baseline , as well as a reduction of weight and entering late puberty stages during follow-up . Cardiovascular risk factors and HOMA improved along with the improvement of IGT , supporting an association between IGT , insulin resistance and features of the metabolic syndrome Summary In a prospect i ve population -based study of middle-aged Caucasian men , performed in Malmö , Sweden , specifically design ed to evaluate physical fitness , early and late insulin response as predictors of non-insulin-dependent diabetes mellitus ( NIDDM ) , 4,637 non-diabetic men underwent oral glucose tolerance tests at the ages of 48 and 54 years . At the baseline examination , physical fitness was measured in terms of lung vital capacity and oxygen uptake during ergometry ; early insulin response in terms of the 40-min insulin increment during an oral glucose tolerance test ( a correlate of acute insulin response to an intravenous glucose tolerance test ) , and late insulin response were measured in terms of the 2-h insulin value during the oral glucose tolerance test ( a correlate of glucose disposal during euglycaemic clamp testing ) . Of the subjects studied 116 developed NIDDM ( 0.4 % annually ) , and when compared with non-diabetic men at baseline , they were found to have an 11 % higher mean body mass index ( p<0.001 ) , a higher frequency of family history of diabetes ( 31 vs 18 % , p<0.001 ) , 16 % lower mean physical activity index ( p<0.05 ) , 16 % lower mean estimated maximal oxygen uptake ( p<0.001 ) , 10 % lower mean vital capacity ( p<0.001 ) , 26 % lower 40-min to total insulin response ratio ( p<0.001 ) , and a 2.7 times higher mean 2-h insulin value during an oral glucose tolerance test ( p<0.001 ) . Regression analysis ( using Cox 's proportional hazards model ) showed both low vital capacity , and impaired early insulin response but late hyperinsulinaemia to be independent predictors of NIDDM , in addition to body mass index and fasting blood glucose level ( p=0.05−0.0001 ) . Among subjects with impaired glucose tolerance at baseline ( 44 of 278 developed NIDDM ) , fasting glucose level alone predicted diabetes in this model . The findings suggest that in this age group in a Caucasian population , not only does insulin resistance precede glucose intolerance and NIDDM , but also loss of early insulin response indicating impaired beta-cell function to be an early feature of the process culminating in diabetes . As both physical fitness [ which correlates inversely with late insulin response ( r=−0.42 , p<0.0001 ) ] , and the level of physical activity were shown to correlate with diabetes development in this large series , measures to correct these adverse features should be included in future strategies for preventing NIDDM We determined in non-diabetic persons the risk of fasting and non-fasting glucose levels for pre-diabetes , diabetes , and coronary heart disease ( CHD ) , including the roles of serum C-reactive protein ( CRP ) and HDL cholesterol , and delineated risk profiles of the pre-diabetic states . Over 7¼ years , 2,619 middle-aged Turkish adults free of diabetes and CHD were studied prospect ively . Using different serum glucose categories including impaired fasting glucose ( IFG , 6.1–6.97 mmol/L ) and impaired glucose tolerance ( IGT ) , outcomes were analyzed by Cox regression . IFG was identified at baseline in 112 and IGT in 33 participants . Metabolic syndrome components distinguished individuals with IFG from those with normoglycemia . Participants with IGT tended to differ from adults in normal postpr and ial glucose categories in regard to high levels of triglycerides , apoA-I , and CRP . Diabetes risk , adjusted for sex , age , waist circumference , CRP , and HDL cholesterol , commenced at a fasting 5.6–6.1 mmol/L threshold , was fourfold at levels 6.1–6.97 mmol/L. Optimal glucose values regarding CHD risk were 5.0–6.1 mmol/L. Fasting and postpr and ial glucose values were not related to CHD risk in men ; IGT alone predicted risk in women ( HR 3.74 [ 1.16;12.0 ] ) , independent of age , systolic blood pressure , non-HDL cholesterol , waist circumference , smoking status , and CRP . HDL cholesterol was unrelated to the development of IFG , IGT , and diabetes , while CRP elevation independently predicted the development of diabetes . IGT independently predicts CHD risk , especially in women . HDL dysfunction associated with low- grade inflammation is a co-determinant of pre-diabetic states and their progression to diabetes INTRODUCTION Incidence of diabetes is increasing at an alarming rate worldwide . It has been estimated that 2.2 to 2.5 million of Poles will be affected by this disease by 2030 . OBJECTIVES The aim of the study was to conduct an epidemiological analysis of the incidence of diabetes and impaired fasting glucose ( IFG ) in the Polish population . PATIENTS AND METHODS A sample of 21,600 individuals ( men and women ) aged 20 - 74 years was r and omly selected from the general Polish population . A total of 14,769 individuals took part in the study ( 6977 men and 7792 women ) . Diabetes was identified in individuals with fasting glucose equal to or exceeding 7 mmol/l and in those with previously diagnosed diabetes . IFG was identified in nontreated individuals with fasting glucose between 5.6 and 6.9 mmol/l . RESULTS Diabetes was diagnosed in 1000 individuals ( 6.8 % ) , including 518 men ( 7.4 % ) and 482 women ( 6.2 % ) . IFG was detected in 1401 individuals ( 9.5 % ) , including 864 men ( 12.4 % ) and 537 women ( 6.9 % ) . Incidence of diabetes increases with age : in men from 0.7 % in those aged 20 - 29 years to 16.3 % in those aged > 60 years ; in women from 0.5 % in the youngest age group to 17.8 % in the oldest group . Incidence of diabetes in Pol and varies between the provinces -- from 5.3 % to 9 % among men and from 4.2 % to 7.5 % among women . There was no significant correlation between the incidence of diabetes and the size of a particular local district ( commune ; gmina ) . Similar territorial differences were observed for IFG , i.e. , from 5.8 % to 20.8 % among men and from 2.8 % to 11.7 % among women . As with diabetes , the incidence of IFG was not associated with the size of a commune . CONCLUSIONS Incidence of diabetes and IFG in the study population varies depending on age , sex , and region . Incidence of diabetes in Pol and is comparable to the average values observed worldwide BACKGROUND Dietary and exercise data are frequently recorded in clinical research , but their correlation with metabolic measures needs further evaluation . OBJECTIVE We examined the association of food and exercise habits with body size , lipid profile , and glycemia in a prospect i ve biracial cohort . METHODS The Pathobiology of Prediabetes in A Biracial Cohort study followed initially normoglycemic offspring of parents with type 2 diabetes ( T2DM ) for the occurrence of incident prediabetes , defined as impaired fasting glucose ( IFG ) and /or impaired glucose tolerance ( IGT ) . At enrollment , participants underwent a 75-gram OGTT , anthropometry , measurement of fasting lipids , insulin , and body fat ( DEXA ) , and completed the Food Habits Question naire ( FHQ ) , and Modifiable Activity Question naire ( MAQ ) . We assessed the relationship between FHQ and MAQ scores and adiposity , cardiometabolic measures , and incident dysglycemia . RESULTS Among our cohort of 338 subjects ( 188 black , 150 white ; mean age { ±SD } 45.2±10.2 years , BMI 30.3±7.2 kg/m(2 ) ) , FHQ and MAQ scores were individually correlated with BMI ( r=0.14 , -0.12 ; P=0.01 , 0.03 ) and waist circumference ( r=0.19 , -0.11 ; P=0.004 , 0.05 ) . Diet-adjusted leisure activity ( MAQ/FHQ ) was significantly correlated with total body fat ( r=-0.20 , P=0.0007 ) , trunk fat ( r=-0.20 , P=0.0006 ) , and serum triglycerides ( r=-0.17 , P=0.003 ) and HDL cholesterol ( r=0.11 , P=0.04 ) levels . During 5.5 years of follow-up , 111 subjects ( Progressors ) developed prediabetes ( n=101 ) or diabetes ( n=10 ) and 227 remained normoglycemic ( Non-progressors ) . Age , BMI , MAQ and MAQ/FHQ values were significant predictors of incident prediabetes/diabetes . Progressors reported similar dietary habits ( FHQ score 2.57±0.49 vs. 2.57±0.53 ) but 30 % lower physical activity ( MAQ score 15.2±20.5 vs. 22.3±30.5 MET-hr/wk , P=0.015 ) compared with non-progressors . CONCLUSIONS Among African-American and Caucasian offspring of parents with T2DM , self-reported dietary and exercise habits correlated with measures of adiposity and dyslipidemia ; however , physical activity , but not dietary recall , significantly predicted incident dysglycemia during 5.5 years of follow-up Background Various strategies have been used to induce lifestyle changes to reduce ischaemic heart disease ( IHD ) with various successes . The aim of Inter99 is to assess the effect on IHD incidence of individually tailored non-pharmacological intervention on lifestyle using a newly developed computer-based health educational tool . The article describes the study and baseline results . Methods From a population of 61,301 individuals two r and om sample s ( high intensity intervention group ( A ) , n = 11,708 ; low intensity intervention group ( B ) , n = 1308 ) are screened to assess their absolute risk of IHD . Those at high risk receive individual lifestyle counselling . Individuals in group A are furthermore offered lifestyle counselling in groups on smoking cessation or physical activity/diet over a 6-month period . Individuals in group B are referred to their GP . High-risk persons are re-counselled after 1 and 3 years and the whole group is re-invited after 5 years . The remaining 48,285 ( group C ) are followed by question naire . The total population is followed through central registers . Intermediate end-points are changes in lifestyle , cholesterol , blood pressure and body mass index . Final end-point is reduction in incidence of IHD . Results The r and omization leads to comparable groups . Participation rate was 52.5 % . A total of 60 % fulfilled the predetermined criteria for being at high risk for developing IHD . After an individual lifestyle counselling 41 % accepted group-based counselling . Conclusion This large r and omized population based trial discloses a noticeable need for and acceptance of lifestyle intervention in the general population . Eur J Cardiovasc Prevention Rehab 10:377 - 386 © 2003 Lippincott Williams & Wilkins Risk factors for non-insulin-dependent diabetes mellitus ( NIDDM ) were assessed in a population of 5042 middle-aged white men , initially nondiabetic , who were followed 3 yr . The subjects were participants in the Paris Prospect i ve Study I. Sixty-three subjects developed diabetes during the follow-up . Plasma glucose concentration in the years before the occurrence of the disease was a major risk factor . Subjects with normal glucose tolerance but elevated fasting plasma glucose exhibited a similar risk of developing NIDDM as did subjects classified as having impaired glucose tolerance on the basis of 2-h postload glucose . In a multiple logistic regression , a high fasting plasma insulin concentration and a low 2-h plasma insulin concentration after a glucose load in association with a high body mass index were independent predictors of conversion to NIDDM from impaired glucose tolerance . Previously , this result had been found only in Nauruans , Pima Indians , and Japanese . This demonstrates for the first time in a white population that a high fasting and low 2-h insulin concentration is predictive of conversion to NIDDM from impaired glucose tolerance The aims of this study were to determine if impaired fasting glucose should be redefined as a fasting plasma glucose ( FPG ) of 100 to 125 mg/dL ( 5.6 - 6.9 mmol/L ) in Korea . A prospect i ve cohort study was undertaken involving 13189 male workers aged 30 to 59 years who did not have medication for diabetes , a history of any cancer , or a fasting glucose level of 126 mg/dL or higher at the initial examination between January 1999 to December 2000 . Subjects were reexamined at periodic annual health examination over a 5-year period . The receiver operating characteristic curve for predicting the future onset of diabetes was derived by plotting the sensitivity against 1 - specificity for a baseline FPG of less than 126 mg/dL. The age- and body mass index-adjusted incidence density of type 2 diabetes mellitus was examined according to the percentile of the distribution for the baseline FPG . The baseline FPG for predicting the future onset of diabetes at a point on the receiver operating characteristic curve that was closest to the ideal 100 % sensitivity and 100 % specificity was 92 mg/dL. There was a threshold for the age- and body mass index-adjusted incidence density of diabetes in the group with FPG of 93 to 95 mg/dL , at a mean of 93.9 mg/dL. Lowering the lower limit of impaired fasting glucose to 100 mg/dL ( 5.6 mmol/L ) would optimize its sensitivity and specificity for predicting the future onset of diabetes in Korea Summary Although an increased plasma non-esterified fatty acid ( NEFA ) concentration has been shown to increase insulin resistance ( R and le cycle ) , decrease insulin secretion and increase hepatic gluconeogenesis , the effect of NEFA on the deterioration of glucose tolerance has not been studied prospect ively in Caucasian subjects . Therefore , we investigated whether plasma NEFA may be regarded as predictors of deterioration of glucose tolerance in subjects with normal ( NGT , n = 3671 ) or impaired ( IGT , n = 418 ) glucose tolerance who were participants in the Paris Prospect i ve study . The subjects were first examined between 1967 and 1972 and underwent two 75-g oral glucose tolerance tests 2 years apart with measurements of plasma glucose , insulin and NEFA concentrations . Glucose tolerance deteriorated from NGT to IGT or non-insulin-dependent diabetes ( NIDDM ) in 177 subjects and from IGT to NIDDM in 32 subjects . In multivariate analysis , high fasting plasma NEFA in NGT subjects and high 2-h plasma NEFA and low 2-h plasma insulin concentrations in IGT subjects were significant independent predictors of deterioration along with older age , high fasting and 2-h plasma glucose concentrations and high iliac to thigh ratio . When subjects were divided by tertiles of plasma NEFA concentration at baseline , there was an increase in 2-h glucose concentration with increasing NEFA in the subjects who did not deteriorate , but no effect of plasma NEFA in those who deteriorated . In subjects with IGT who deteriorated compared with those who did not 2-h plasma insulin concentration was lower but there was no evidence that this result ed from an effect of plasma NEFA . Our data suggest that a high plasma NEFA concentration is a risk marker for deterioration of glucose tolerance independent of the insulin resistance or the insulin secretion defect that characterize subjects at risk for NIDDM . [ Diabetologia ( 1997 ) 40 : 1101–1106 To clarify whether pancreatic beta-cell function and /or insulin resistance contributes to development of glucose intolerance in Japanese subjects , we investigated 551 subjects who underwent a 75-g oral glucose tolerance test ( OGTT ) . Subjects were divided into 3 groups : normal glucose tolerance ( NGT , n = 238 ) , impaired glucose tolerance ( IGT , n = 211 ) , and newly diagnosed type 2 diabetes mellitus ( n = 102 ) . The diabetics were subdivided into 3 subgroups as follows : diabetes with normal fasting glucose ( fasting plasma glucose [ FPG ] < 110 mg/dL ) , diabetes with impaired fasting glucose ( FPG 110 to 125 mg/dL ) , and diabetes with diabetic fasting glucose ( FPG > or= 126 mg/dL ) . Insulinogenic index as early-phase insulin secretion , homeostasis model assessment ( HOMA-beta and HOMA-resistance ) , and 4 different formulas of insulin sensitivity index were assessed by plasma glucose and insulin concentrations obtained at fasting or during a 75-g OGTT . Both early-phase insulin secretion and insulin sensitivity were low even in the IGT stage compared with NGT . The transition from IGT to diabetes was accompanied by a progressive deterioration of insulin reserve as well as insulin resistance . During the further progression in diabetes , insulinogenic index decreased additionally , whereas declines in insulin sensitivity were relatively small . In conclusion , both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of glucose intolerance in Japanese subjects AIM Because the incidence of type 2 diabetes in Korea has not been clearly defined , we examined the incidence of this condition and its association with impaired fasting glucose ( IFG ) , impaired glucose tolerance ( IGT ) , and other risk factors in a 12-year follow-up Korean community-based prospect i ve cohort study . METHODS We recruited 7542 subjects aged 40 - 69years without diabetes at baseline examination from the Korean Genome and Epidemiology Study and followed these subjects for 12years biennially . Diabetes was defined according to the 2010 American Diabetes Association criteria . The incidence of type 2 diabetes and the predictors of progression to diabetes were analyzed according to baseline glucose tolerance . RESULTS The overall incidence of type 2 diabetes was 22.1 per 1000person-years . Subjects with combined IFG-IGT at baseline had the highest incidence of diabetes , which was more than two-fold that of individuals with isolated IFG or isolated IGT ( 114.4 vs. 51.3 vs. 53.1 per 1000person-years ) . A multivariate Cox proportional hazards model analysis showed that combined IFG-IGT , which were strong predictors of diabetes , as well as age , urban residence , family history of diabetes , smoking status , abdominal obesity , hypertension , high triglycerides and low HDL cholesterols were also independently associated with progression to diabetes . CONCLUSIONS The incidence of type 2 diabetes is relatively high in our Korean community-based sample . Combined IFG-IGT are strong predictors of type 2 diabetes . Measurement of 2-hour plasma glucose in addition to fasting plasma glucose is necessary for the detection of individuals at high risk for development of diabetes OBJECTIVE To prospect ively evaluate progression to diabetes in individuals with impaired glucose regulation as defined according to fasting glucose alone or an oral glucose tolerance test ( OGTT ) ( i.e. , both fasting and postload glucose ) to compare the ability of these two screening methods to identify people at high risk of developing diabetes . RESEARCH DESIGN AND METHODS A working population of 1,245 nondiabetic telephone company employees aged 40 - 59 years was studied by OGTT in 1980 . Participants were classified according to baseline fasting glucose only ( as encouraged by the American Diabetes Association [ ADA ] ) or OGTT ( as recommended by the 1998 World Health Organization [ WHO ] consultation ) . Progression to diabetes was evaluated 11.5 years later according to the 1997 ADA criteria of a fasting plasma glucose level > or = 7.0 mmol/l . RESULTS With the use of the OGTT , baseline prevalence of impaired glucose regulation was substantially higher than that with fasting glucose alone ( 7.2 vs. 3.2 % ) ; the two groups only overlap for 40.9 % of the cases because a fairly large number of people with postload hyperglycemia ( 59.1 % ) have normal fasting glucose . Progression to diabetes in participants with normal fasting glucose and postload hyperglycemia is significantly more frequent than that of people with normoglycemia ( 32.5 vs. 7.2 % ; P < 0.001 ) and not significantly different from that of people with both fasting and postload hyperglycemia ( i.e. , 44.0 % ) . However , the former are not identified as being at unusually high risk of diabetes unless an OGTT is performed . When the use of fasting glucose alone or OGTT was vali date d as a marker of progression to diabetes , sensitivity was substantially higher for the OGTT ( 33.3 vs. 9.0 % ) without major differences in specificity ( 92.6 vs. 97.0 % ) . CONCLUSIONS These data ( the only data so far available in Caucasians ) support the viewpoint that for the identification of people at high risk of diabetes , the use of the OGTT should be maintained Type 2 diabetes is a common disease in industrialized countries . It is a major cause of cardiovascular disease and all-cause mortality ( 1 - 6 ) , and its prevalence has increased continuously over the past few decades ( 1 ) . The American Diabetes Association currently defines impaired fasting glucose as a fasting plasma glucose level from 6.1 to 6.9 mmol/L ( 110 to 125 mg/dL ) and type 2 diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Data from several prospect i ve studies show an inverse association between physical activity and diabetes ( 7 - 13 ) . However , these studies are limited by the use of self-reporting of physical activity and presence of type 2 diabetes ( 7 - 12 ) . Self-reporting of physical activity tends to be imprecise , and type 2 diabetes is undiagnosed in about 50 % of the prevalent cases ( 14 ) . This leads to misclassification on both exposure and outcome measures ( 15 ) . These limitations may result in underestimation of the true association between sedentary habits and risk for type 2 diabetes . Impaired fasting glucose is a strong predictor of type 2 diabetes , cardiovascular disease , and other diabetic complications ( 6 , 16 - 18 ) . The underlying cause of impaired fasting glucose is unknown , and no prospect i ve study of the association between physical activity and impaired fasting glucose has been published . We examined the relation of cardiorespiratory fitness , objective ly determined by a maximal exercise test on a treadmill , to the incidence of impaired fasting glucose and type 2 diabetes . Cases of impaired fasting glucose and diabetes at baseline and follow-up were determined by using the American Diabetes Association 's current guidelines ( 1 ) . Methods Patients In our population -based prospect i ve study , we included 8633 men 30 to 79 years of age at baseline ( mean , 43.5 years ) who completed at least two medical evaluations at the Cooper Clinic in Dallas , Texas , from 1970 to 1995 . Patients come to the Cooper Clinic for preventive medical examinations and health promotion counseling . Many are sent by their employers for these services , some are referred by their personal physicians , and others are self-referred . More than 97 % of the patients are white , and most are employed in executive or professional occupations . More than 75 % are college graduates . Although study participants came from middle and upper socioeconomic strata , they were similar to other well-characterized population -based cohorts in terms of blood pressure , cholesterol level , body weight , and cardiorespiratory fitness ( 19 ) . The study was review ed and approved annually by the institutional review board at the Cooper Institute for Aerobics Research . Additional details of the study methods and population characteristics of the cohort have been published elsewhere ( 20 , 21 ) . Because clinical or sub clinical heart disease and other conditions associated with type 2 diabetes may alter the level of physical activity and thus cardiorespiratory fitness , we excluded men with an abnormal resting or exercise electrocardiogram or a history of heart attack , stroke , or cancer at the baseline clinical examination ( n=2350 ) . The baseline evaluation was performed after participants gave written informed consent for the initial medical examination and registration in the follow-up study . Examinations were done after patients had fasted for at least 12 hours and included personal and family health histories , a question naire on demographic characteristics and health habits , a physical examination , an exercise test , anthropometric measurement , electrocardiography , blood chemistry analyses , and blood pressure measurement . Technicians who followed a st and ard manual of operations administered all procedures . Impaired fasting glucose and type 2 diabetes were diagnosed according to American Diabetes Association criteria that define impaired fasting glucose as a fasting plasma glucose level of 6.1 to 6.9 mmol/L ( 110 mg/dL to 125 mg/dL ) and diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Patients who did not meet these criteria but who reported a history of diabetes or current therapy with oral antidiabetic agents or insulin were also considered to have diabetes . We excluded patients who had diabetes at baseline according to any of these criteria ( n=377 ) . Cardiorespiratory fitness was assessed with a maximal exercise test that followed a modified Balke protocol ( 22 ) . Details of treadmill speed and elevation have been described elsewhere ( 20 , 21 ) . Briefly , the test began with the patient walking on a horizontal treadmill at 88 m/min . After the first minute , the elevation increased to 2 % ; the elevation then increased 1 % each minute up to 25 minutes . For the few patients who were still able to continue , the elevation was held constant after 25 minutes and the speed was increased by 5.4 m/min until the patient reached volitional fatigue . Use of this protocol for the exercise test correlates highly ( r=0.92 ) with measured maximal oxygen uptake ( 23 ) . All patients in our study achieved at least 85 % of their age-predicted maximal heart rate ; average maximal heart rates ( SD ) in each age group were 186 11 beats/min for patients 30 to 39 years of age , 179 12 beats/min for those 40 to 49 years of age , 172 13 beats/min for those 50 to 59 years of age , and 162 17 beats/min for those 60 years of age or older . Average maximal heart rates in each age group exceeded the age-predicted rate ( 220 beats/min age in years ) , which indicates that the exercise test can be considered maximal performance . We defined level of fitness by total time on the treadmill at the baseline examination , as in our previous studies ( 20 , 21 ) . Treadmill times were placed in frequency distributions for specific age groups ( 30 to 39 , 40 to 49 , 50 to 59 , or 60 or more years of age ) . The least fit 20 % of the participants in each age group were classified as low fitness , the next 40 % as moderate fitness , and the remaining 40 % as high fitness . The respective cut-points for total treadmill time in the low- , moderate- , and high-fitness groups were 945 seconds or less , 946 to 1259 seconds , and 1260 seconds or more for patients 30 to 39 years of age ; 849 seconds or less , 850 to 1020 seconds , and 1021 seconds or more for patients 40 to 49 years of age ; 750 seconds or less , 751 to 1035 seconds , and 1036 seconds or more for patients 50 to 59 years of age ; and 644 seconds or less , 645 to 953 seconds , and 954 seconds or more for patients 60 years of age or older . These cut-points at the 20th and 60th percentiles to define fitness levels were used in previous studies ( 20 , 21 ) and were selected before analysis for our investigation . However , we calculated these cut-points with patients in the current study , from which unhealthy persons were excluded . Therefore , they differ somewhat from the cut-points derived from the entire cohort of the Aerobics Center Longitudinal Study ( 21 ) . For some analyses , such as the models that included change in fitness from baseline to follow-up , cardiorespiratory fitness was expressed as maximal metabolic units ( metabolic equivalents [ METs ] , calculated as the working metabolic rate/resting metabolic rate ; 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg1 ) achieved on the exercise test . In other analyses , time on the treadmill was used as a continuous variable . Serum sample s were analyzed by using automated techniques in a laboratory that participates in the Centers for Disease Control and Prevention Lipid St and ardization Program . Blood pressure was measured by using auscultatory methods with a mercury sphygmomanometer . We defined high blood pressure as systolic blood pressure of at least 140 mm Hg , diastolic blood pressure of at least 90 mm Hg , or a history of hypertension . Height and weight were measured with a st and ard physician 's scale and stadiometer , and body mass index was calculated as weight in kg/height in m2 . Waist circumference was measured with a st and ard anthropometric tape . Statistical Analysis We used SAS statistical software for data analyses ( 24 ) . The incidence of impaired fasting glucose was calculated for men with normal fasting glucose at baseline , and the incidence of diabetes was based on data from all 8633 patients . For analyses with impaired fasting glucose as the outcome , we excluded 1122 men who had impaired fasting glucose at baseline and an additional 69 men who had normal fasting plasma glucose at baseline but developed diabetes during follow-up . Rates of impaired fasting glucose or diabetes were calculated by dividing the number of incident cases during the study period by the number of person-years over the same period . We defined the study period as the interval between the baseline examination and the last follow-up visit . We used logistic regression to estimate the association between dependent variables and independent variables after adjustment for possible confounding factors . We used general linear models to study the cross-sectional association of fitness level and parental history of diabetes ( 24 , 25 ) . To account for the possible cohort effect of baseline year , we examined the relation between incident cases and baseline year and found no association . We used tests for ordinal linear trend to evaluate the possible relation of higher treadmill time with risk for impaired fasting glucose or diabetes after dividing the sample into the three fitness groups . All P values are two-sided , and those less than 0.05 were considered statistically significant . Role of the Funding Source The funding agencies did not participate in the collection , analysis , or interpretation of data presented in this report or in the decision to su bmi t the manuscript for publication . Results During an average follow-up of 6.1 4.8 years ( range , 1 to 24.8 years ) that included 52 588 person-years , 593 men developed impaired fasting glucose and 149 developed diabetes . Of the men with incident diabetes , 139 ( 93 % ) were not aware of OBJECTIVES Noninsulin-dependent diabetes mellitus , a major risk factor for cardiovascular disease , is prevalent in more than 12 million Americans . A voluminous amount of data demonstrates that cigarette smoking is an important cause of cancer and coronary heart disease . However , the association between cigarette smoking and the risk of diabetes is virtually unexplored , especially in women . METHODS We examined the association between smoking and the incidence of noninsulin-dependent diabetes mellitus among 114,247 female nurses who were free of diabetes , cardiovascular disease , and cancer in 1976 . We collected exposure information and disease status prospect ively for 12 years from biennially self-administered question naires . RESULTS Current smokers had an increased risk of diabetes , and we observed a significant dose-response trend for higher risk among heavier smokers . During 1,277,589 person-years of follow-up , 2333 women were clinical ly diagnosed with diabetes . The relative risk of diabetes , adjusted for obesity and other risk factors , was 1.42 among women who smoked 25 or more cigarettes per day compared with nonsmokers . CONCLUSIONS These data suggest that cigarette smoking may be an independent , modifiable risk factor for noninsulin-dependent diabetes mellitus Aims /hypothesisThe aim of this study was to assess the impact of invitation to screening for type 2 diabetes and related cardiovascular risk factors on population mortality . Methods This was a parallel-group population -based cohort study including all men and women aged 40–65 years , free of known diabetes , registered with a single practice in Ely , UK ( n = 4,936 ) . In 1990–1992 , approximately one-third ( n = 1,705 ) were r and omly selected to receive an invitation to screening for diabetes ( with an OGTT ) and related cardiovascular risk factors . In the remaining two-thirds of the population , 1,705 individuals were r and omly selected for invitation to screening in 2000–2003 and 1,526 were not invited at any point during the follow-up period . All individuals were flagged for mortality until January 2008 . Results There were 345 deaths between 1990 and 1999 ( median 10 years follow-up ) . Compared with those not invited , individuals who were invited to the 1990–1992 screening round had a non-significant 21 % lower all-cause mortality ( HR 0.79 [ 95 % CI 0.63–1.00 ] , p = 0.05 ) after adjustment for age , sex and deprivation . There were 291 deaths between 2000 and 2008 ( median 8 years follow-up ) , with no significant difference in mortality between invited and non-invited participants in 2000–2003 . Compared with the non-invited group , participants who attended for screening at any time point had a significantly lower mortality and those who did not attend had a significantly higher mortality . Conclusions /interpretationInvitation to screening was associated with a non-significant reduction in mortality in the Ely cohort between 1990 and 1999 , but this was not replicated in the period 2000–2008 . This study contributes to the evidence concerning the potential benefits of population screening for diabetes and related cardiovascular risk factors AIM To develop strategies based on simple clinical assessment and blood markers to identify older individuals at high risk for Type 2 diabetes . METHODS A prospect i ve study of non-diabetic men ( n = 3523 ) and women ( n = 3404 ) aged 60 - 79 years followed for 7 years , during which there were 297 incident cases of Type 2 diabetes . Logistic regression was used to develop scores to predict incident cases , starting with clinical predictors and adding blood markers that predicted the incidence of diabetes . Receiving operating characteristic analyses were used to assess improvement in prediction . RESULTS The area under the curve for a simple clinical assessment score , which included age , sex , family history of diabetes , smoking status , BMI , waist circumference , hypertension and recall of doctor diagnosis of coronary heart disease was 0.765 ( 0.740 , 0.791 ) ; sensitivity and specificity in the top quintile of the score were 50.3 and 81.4 % , respectively . Addition of simple fasting blood markers HDL cholesterol , triglyceride and glucose improved prediction [ area under the curve = 0.817 ( 0.793 , 0.840 ) , P < 0.0001 ; sensitivity 63.8 % ; specificity 82.0 % ] . An alternative model adding blood markers not dependent on fasting yielded similar results . Further addition of C-reactive protein made no improvement . Blood measurements made small differences to reclassification of risk in those in the lowest three quintiles of the non-laboratory score . CONCLUSION In large population setting s , simple clinical assessment s could be used in the first instance to identify older adults who would benefit from further testing with routine ( non-fasting ) blood markers to identify those at most likely to be at elevated diabetes risk BACKGROUND Our objective was to quantify and predict diabetes risk reduction during the Diabetes Prevention Program Outcomes Study ( DPPOS ) in participants who returned to normal glucose regulation at least once during the Diabetes Prevention Program ( DPP ) compared with those who consistently met criteria for prediabetes . METHODS DPPOS is an ongoing observational study of participants from the DPP r and omised trial . For this analysis , diabetes cumulative incidence in DPPOS was calculated for participants with normal glucose regulation or prediabetes status during DPP with and without stratification by previous r and omised treatment group . Cox proportional hazards modelling and generalised linear mixed models were used to quantify the effect of previous ( DPP ) glycaemic status on risk of later ( DPPOS ) diabetes and normal glucose regulation status , respectively , per SD in change . Included in this analysis were 1990 participants of DPPOS who had been r and omly assigned to treatment groups during DPP ( 736 intensive lifestyle intervention , 647 metformin , 607 placebo ) . These studies are registered at Clinical Trials.gov , NCT00004992 ( DPP ) and NCT00038727 ( DPPOS ) . FINDINGS Diabetes risk during DPPOS was 56 % lower for participants who had returned to normal glucose regulation versus those who consistently had prediabetes ( hazard ratio [ HR ] 0·44 , 95 % CI 0·37 - 0·55 , p<0·0001 ) and was unaffected by previous group assignment ( interaction test for normal glucose regulation and lifestyle intervention , p=0·1722 ; normal glucose regulation and metformin , p=0·3304 ) . Many , but not all , of the variables that increased diabetes risk were inversely associated with the chance of a participant reaching normal glucose regulation status in DPPOS . Specifically , previous achievement of normal glucose regulation ( odds ratio [ OR ] 3·18 , 95 % CI 2·71 - 3·72 , p<0·0001 ) , increased β-cell function ( OR 1·28 ; 95 % CI 1·18 - 1·39 , p<0·0001 ) , and insulin sensitivity ( OR 1·16 , 95 % CI 1·08 - 1·25 , p<0·0001 ) were associated with normal glucose regulation in DPPOS , whereas the opposite was true for prediction of diabetes , with increased β-cell function ( HR 0·80 , 95 % CI 0·71 - 0·89 , p<0·0001 ) and insulin sensitivity ( HR 0·83 , 95 % CI 0·74 - 0·94 , p=0·0001 ) having a protective effect . Among participants who did not return to normal glucose regulation in DPP , those assigned to the intensive lifestyle intervention had a higher diabetes risk ( HR 1·31 , 95 % CI 1·03 - 1·68 , p=0·0304 ) and lower chance of normal glucose regulation ( OR 0·59 , 95 % CI 0·42 - 0·82 , p=0·0014 ) than did the placebo group in DPPOS . INTERPRETATION We conclude that prediabetes is a high-risk state for diabetes , especially in patients who remain with prediabetes despite intensive lifestyle intervention . Reversion to normal glucose regulation , even if transient , is associated with a significantly reduced risk of future diabetes independent of previous treatment group . FUNDING US National Institutes of Health BACKGROUND The objective was to study the ability of the 30-min plasma glucose ( 30-min PG ) during an oral glucose tolerance test to predict the future risk of type 2 diabetes among Asian Indians with impaired glucose tolerance . METHODS For the present analyses , we utilized data from 753 participants from two diabetes primary prevention studies , having complete data at the end of the study periods , including 236 from Indian Diabetes Prevention Programme-1 and 517 from the 2013 study . Baseline 30-min PG values were divided into tertiles : T1 < 9.1 mmol/L ( < 163.0 mg/dL ) ; T2 9.2 - 10.4 mmol/L ( 164.0 - 187.0 mg/dL ) and T3 ≥ 10.4 mmol/L ( ≥188 mg/dL ) . The predictive values of tertiles of 30-min PG for incident diabetes were assessed using Cox regression analyses RESULTS : At the end of the studies , 230 ( 30.5 % ) participants developed diabetes . Participants with higher levels of 30-min PG were more likely to have increased fasting , 2-h PG and HbA1c levels , increased prevalence of impaired fasting glucose and decreased beta cell function . The progression rate of diabetes increased with increasing tertiles of 30-min PG . Cox 's regression analysis showed that 30-min PG was an independent predictor of incident diabetes after adjustment for an array of covariates [ Hazard Ratio (HR):1.44 ( 1.01 - 2.06 ) ] CONCLUSIONS : This prospect i ve analysis demonstrates , for the first time , an independent association between an elevated 30-min PG level and incident diabetes among Asian Indians with impaired glucose tolerance . Predictive utility of glycemic thresholds at various time points other than the traditional fasting and 2-h PG values should therefore merit further consideration . Copyright © 2016 John Wiley & Sons , BACKGROUND The long-range prediction from clinical variables of the onset of diabetes is important to patients and clinicians . Our objective was to evaluate the efficacy of various glucose-related clinical measurements in predicting the 20-year risk of developing type 2 diabetes ( T2DM ) in an elderly population . METHODS In a prospect i ve study , 672 men and women aged 59 - 92 years , who were not diabetic in 1980 and were part of a nationwide longitudinal r and omized study , were followed-up in 2000 - 2003 . Fasting glucose , 1- and 2-h post-oral glucose tolerance and insulin were measured in 1980 and 2000 - 2003 . RESULTS A group of 174 ( 25.9 % ) survivors had progressed to diabetes during the 20-year follow-up . Fasting glucose values were a good predictor for diabetes . With the 100 mg/dL cut-off of impaired fasting glucose ( IFG ) , a 2 - 4-times higher predictive sensitivity followed the dramatic increase in IFG prevalence compared to the 110 mg/dL cut-off , but at a cost of reduced specificity and positive predictive value ( PPV ) . By receiver operating curve ( ROC ) analysis , a 1-h post-load glucose was similar to 2 h and fasting glucose in prediction of the 20-year incidence of diabetes , and classifying correctly the 77 , 74 and 73 % of the group , respectively . In adjusted logistic regressions , 2.28 , 1.78 and 1.69-folds increased the 20-year risk , and were associated with each SD increment of the respective glucose values ( p < 0.001 ) . CONCLUSIONS Although the best population -based strategy for the diagnosis of T2DM would be the combination of fasting glucose followed by post-load glucose , for the purpose s of long-term prediction of T2DM risk , fasting glucose is sufficient AIMS We assessed blood pressure ( BP ) and blood glucose ( BG ) values in healthy subjects , and examined baseline BP as a predictor of incident prediabetes during follow-up . METHODS Participants in the Pathobiology of Prediabetes in a Biracial Cohort ( POP-ABC ) study underwent screening assessment s ( anthropometry , BP , OGTT ) and were stratified into normal BP ( NBP ) , prehypertension , or hypertension , and normal glucose regulation ( NGR ) , prediabetes ( IFG/IGT ) , or type 2 diabetes ( T2D ) status . NGR subjects who met all inclusion criteria were enrolled in a 5-yr prospect i ve study , with the primary outcome of incident prediabetes . RESULTS We screened 602 adults ( 341 black , 261 white ) and enrolled 343 ( 193 black , 150 white ) for prospect i ve follow-up . Systolic and diastolic BP correlated significantly with fasting and nonfasting BG ( P=0.003-<0.0001 ) . Compared to NGR group , more prediabetic subjects had prehypertension ( 42.5 % vs. 36.2 % ) and fewer had NBP ( 35.9 % vs. 48.6 % ) ( P=0.009 ) . During ~5years of follow-up , 26.3 % of NBP and 35.7 % of prehypertensive subjects developed prediabetes ( P=0.02 ) . Kaplan-Meier analysis showed higher probability of incident prediabetes among participants with prehypertension compared to NBP during ~5years of follow-up ( P=0.0012 ) . CONCLUSIONS In our biracial cohort , BP and BG values were significantly correlated , and BP status predicted incident prediabetes among initially normoglycemic individuals . These findings suggest co-evolution of factors involved in the dysregulation of BP and BG The diabetes mellitus of type 2 ( DMT2 ) is a disease of the elderly with multifactorial pathogenesis , characterized by interactions of genetic variations suspect for diabetes , as well as of the longevity and aging genes . Since today it is still not possible to obtain the diagnosis with laboratory methods of clinical genetics , we tried to identify the subjects of risk of future diabetes on the basis of a combined measurement of glycemia , the glycosylated hemoglobin ( HbA1c ) and the waist circumference ( WC ) . The studied population consisted of 2603 elderly subjects of 65 - 84 years of age , involved in the epidemiological study called ILSA ( Italian Longitudinal Study on Aging ) . The subjects who displayed at the baseline an impaired fasting glucose ( IFG ) accompanied by HbA1c and WC values above the normal cut-points proved to be diabetic after a 3-year follow-up in 18.96 % , while the subjects with normal fasting glucose ( NFG ) accompanied by normal HbA1c and WC values were found to be diabetic only in 1.34 % . It means that the presence of abnormal values of these 3 parameters in the elderly does not allow the identification of the risks for future diabetes in the great majority of subjects . We conclude that the results of prospect i ve studies may gain particular significance not only regarding the glycemia , but also the other 2 risk factors , if we wish to reach not only a predictive diagnosis of risk for diabetes , but also to prevent the chronic degenerative complications of it The Isle of Ely Diabetes Project is a prospect i ve population -based study of the aetiology and pathogenesis of Type 2 diabetes mellitus . Between 1990 and 1992 , 1156 subjects aged between 40 and 65 years underwent a st and ard 75 g oral glucose tolerance test ( OGTT ) . A total of 1122 individuals who were not known to have diabetes completed the test and were classified according to WHO criteria ; 51 subjects ( 4.5 % ) had previously undiagnosed diabetes and 188 ( 16.7 % ) had impaired glucose tolerance . The subjects with newly diagnosed glucose intolerance were significantly older , more obese , and shorter than those with normal glucose tolerance . Blood pressure , cholesterol , triglyceride , and LDL-cholesterol concentrations were elevated and HDL-cholesterol levels were lower among those with abnormal rather than normal glucose tolerance . In multiple regression analyses stratified by gender and including age , body mass index , and the waist-hip ratio as covariates , there were significant differences between those with normal and abnormal glucose intolerance in blood pressure , triglyceride , and HDL-cholesterol , but not total or LDL-cholesterol . In both male and female subjects , height had a significant independent negative association with the plasma glucose at 120 min after administration of oral glucose ( st and ardized beta coefficient = -0.12 , p < 0.01 ) This study compared the relative role of insulin resistance and beta-cell dysfunction ( both assessed using the HOMA method ) with glucose intolerance conditions in the progression to type 2 diabetes among a high risk group of subjects with fasting plasma glucose ( FPG ) 5.6 - 7.0 mmol/l in Kinmen , Taiwan . Data were collected during a continuing prospect i ve study ( 1998 - 99 ) of a group of Taiwanese subjects at high-risk of developing type 2 diabetes who had fasting hyperglycemia ( 5.6 - 7.0 mmol/l ) and exhibited 2-h postload glucose concentrations < 11.1 mmol/l from 1992 - 94 to 1995 - 96 . Among 644 non-diabetic subjects at baseline , 79.8 % ( 514/644 ) had at least one follow-up examination . There were 107 new cases of diabetes diagnosed by 1999 WHO criteria in 2918.7 person-years of follow-up . The incidence rate was 3.67%/year ( 107/2918.7 ) . After adjustment for other possible associative variables , including gender , age , BMI , waist circumference , insulin resistance , and beta-cell dysfunction , Cox 's hazard model showed that those individuals with isolated IFG ( impaired fasting glucose ) and those individuals with isolated IGT ( 2-h glucose impairment ) exhibited similar risk of developing diabetes . Those individuals with isolated IFG and isolated IGT showed a comparable impairment of basal or hepatic insulin sensitivity , but those individuals with isolated IFG had a greater beta-cell dysfunction by the HOMA method A longitudinal study of 266 r and omly selected nondiabetic Nauruans [ 215 with normal tolerance and 51 with impaired glucose tolerance ( IGT ) ] over 6 yr showed that deterioration in glucose tolerance status had occurred in 61 subjects . Of the subjects with initially normal tolerance , 34 ( 16 % ) progressed to IGT and 14 ( 6.5 % ) progressed to diabetes . Thirteen of the subjects with IGT ( 25 % ) progressed to diabetes . Subjects were examined in 1975 through 1976 , and follow-up examinations were performed in 1982 . After age , a high 2-h plasma insulin response to a glucose load was the factor most predictiveof progression from normal tolerance to both diabetes ( P < .001 ) and IGT ( P < .01 ) . Both a high 2-h glucose level and greater obesity independently predicted progression from IGT , and a diminished 2-h insulin response just failed to significantly improve the model ( P < .06 ) . The negative parameter of the insulin response associated with deterioration from IGT differed significantly ( P < .01 ) from the positive-parameter estimate of the response associated with progression to diabetes from normal tolerance ( P < .01 ) , implying a qualitative difference between these nondiabetic subgroups . The use of a glucose-insulin interaction term to predict ( P < .01 ) progression to diabetes for all nondiabetic subjects confirmed this difference ; this term 's addition improved the model ( P < .01 ) , and progression to diabetes was associated with a high insulin response for 2-h glucose < 7.8 mM but a low response for 2-h glucose > 7.8 BACKGROUND The Italian Longitudinal Study on Aging ( ILSA ) evaluates the rates of diabetes , cardiovascular and neurological disorders in a r and om sample of 5632 Italians aged 65 - 84 years . METHODS The ILSA has two components : a first screening phase administered to all participants , that includes a personal interview , physician examination , laboratory and diagnostic tests , and a second phase , consisting of the clinical confirmation of suspected cases by a specialist . RESULTS Prevalence rates were significantly higher among men for myocardial infa rct ion ( 10.7 % versus 4.8 % ) , cardiac arrhythmia ( 25.1 % versus 20.3 % ) and peripheral artery disease ( 8.1 % versus 5.2 % ) , and among women for hypertension ( 67.3 % versus 59.4 % ) , heart failure ( 7.3 % versus 5.4 % ) and dementia ( 7.2 % versus 5.3 % ) . No gender difference was found for stroke , angina , diabetes , Parkinsonism and distal symmetric neuropathy . Unreported diagnoses accounted for 85 % of cases of distal symmetric neuropathy , for more than half the cases of cardiac failure , for 40 % of cases of angina , and for more than one-third of cases arrhythmia , myocardial infa rct ion , peripheral artery disease , hypertension , Parkinsonism . Data from the phase 1 interview showed substantial overreporting for myocardial infa rct ion , peripheral artery disease , diabetes , and stroke . CONCLUSIONS The authors conclude that self-reported information would lead to inaccurate estimates of prevalence rates suggesting the need for including the clinical ascertainment in any population -based epidemiological study Aims /hypothesis . To study the risk of women with impaired fasting glucose ( IFG ) as against impaired glucose tolerance ( IGT ) developing diabetes.¶ Methods . Oral glucose tolerance tests ( 75 g ) were done in 265 women selected at r and om at baseline ( age 55–57 years ) and at a 10-year follow-up . Of the women 42 had IFG/NGT ( fasting glucose 6.1–6.9 mmol/l , 2-h glucose < 7.8 mmol/l ) , 66 IGT/NFG ( 2-h glucose 7.8–11.0 mmol/l , fasting glucose < 6.1 mmol/l ) , 30 IGT/IFG and 127 NFG/NGT.¶ Results . The 10-year progression to diabetes was similar in IGT/NFG ( 12.1 % ) and IFG/NGT groups ( 11.9 % , p = 0.97 ) . In IGT/IFG , 20.0 % had developed diabetes , which was not significantly higher than in IFG/NGT and IGT/NFG ( p = 0.53 ) . In NFG/NGT at baseline , only 3.9 % had developed diabetes , which was lower than in the other groups ( p = 0.023).¶ Conclusion /interpretation . Fasting and 2-h glucose concentrations are equally good in predicting diabetes development over a 10-year period in Caucasian postmenopausal women . Because IGT is more common than IFG , measuring only fasting glucose concentrations would , however , result in missing a prediabetic stage in a large group of people at risk for diabetes and cardiovascular diseases . [ Diabetologia ( 2000 ) 43 : 1224–1228 OBJECTIVE To examine prospect ively the association between regular exercise and the subsequent development of non-insulin-dependent diabetes mellitus ( NIDDM ) . DESIGN Prospect i ve cohort study including 5 years of follow-up . PARTICIPANTS 21,271 US male physicians participating in the Physicians ' Health Study , aged 40 to 84 years and free of diagnosed diabetes mellitus , myocardial infa rct ion , cerebrovascular disease , and cancer at baseline . Morbidity follow-up was 99.7 % complete . MAIN OUTCOME MEASURE Incidence of NIDDM . RESULTS At baseline , information was obtained about frequency of vigorous exercise and other risk indicators . During 105,141 person-years of follow-up , 285 new cases of NIDDM were reported . The age-adjusted incidence of NIDDM ranged from 369 cases per 100,000 person-years in men who engaged in vigorous exercise less than once weekly to 214 cases per 100,000 person-years in those exercising at least five times per week ( P , trend , less than .001 ) . Men who exercised at least once per week had an age-adjusted relative risk ( RR ) of NIDDM of 0.64 ( 95 % Cl , 0.51 to 0.82 ; P = .0003 ) compared with those who exercised less frequently . The age-adjusted RR of NIDDM decreased with increasing frequency of exercise : 0.77 for once weekly , 0.62 for two to four times per week , and 0.58 for five or more times per week ( P , trend , .0002 ) . A significant reduction in risk of NIDDM persisted after adjustment for both age and body-mass index : RR , 0.71 ( 95 % Cl , 0.56 to 0.91 ; P = .006 ) for at least once per week compared with less than once weekly , and P , trend , .009 , for increasing frequency of exercise . Further control for smoking , hypertension , and other coronary risk factors did not material ly alter these associations . The inverse relation of exercise to risk of NIDDM was particularly pronounced among overweight men . CONCLUSIONS Exercise appears to reduce the development of NIDDM even after adjusting for body-mass index . Increased physical activity may be a promising approach to the primary prevention of NIDDM AIMS In 2010 , the American Diabetes Association has published recommendations on the population to be screened for dysglycaemia ; the diagnostic criteria for intermediate hyperglycaemia and diabetes using oral glucose tolerance testing and HbA(1c ) ; and the patients eligible for treatment with metformin . We aim ed to evaluate the consequences of screening with oral glucose tolerance test or HbA(1c ) in an at-risk population . METHODS Among 1177 overweight or obese consecutive adults without known diabetes who were referred to our department for weight management , we selected 1157 individuals ( 83 % female ; 80 % European ) fulfilling the American Diabetes Association 2010 criteria for dysglycaemia screening . RESULTS Mean age was 41.2 ± 13 years , BMI 37.0 ± 7.2 kg/m(2 ) , fasting plasma glucose 4.9 ± 0.8 mmol/l and HbA(1c ) ( turbidimetric immunoassay ) 5.7 ± 0.7 % ( 39 mmol/mol ) . Based on oral glucose tolerance test and HbA(1c ) , respectively , 76 ( 6.6 % ) and 113 ( 9.8 % ) patients had diabetes , including 34 sharing both criteria ; 307 ( 26.5 % ) and 478 ( 41.3 % ) had intermediate hyperglycaemia ; and 130 ( 11.2 % ) and 255 ( 22.0 % ) would be treated with metformin . The sensitivity/specificity of HbA(1c ) ≥ 6.5 % ( 48 mmol/mol ) for the diagnosis of diabetes according to the oral glucose tolerance test were 44.7/92.7 % . Diabetes risk scores and UK Prospect i ve Diabetes Study cardiovascular risk score were the highest in the 130 patients having both an abnormal oral glucose tolerance test and HbA(1c ) ≥ 5.7 % . CONCLUSIONS In a population at risk for diabetes , the HbA(1c ) strategy could lead to diagnosing more cases of dysglycaemia and to treating more patients with metformin than the oral glucose tolerance test strategy . The consistency of either diagnostic criteria was low . The patients with the highest a priori risk of diabetes and cardiovascular disease were those fulfilling both oral glucose tolerance test and HbA(1c ) criteria AIM R and om glucose is widely used in routine clinical practice . We investigated whether this non-st and ardized glycemic measure is useful for individual diabetes prediction . METHODS The Study of Health in Pomerania ( SHIP ) , a population -based cohort study in north-east Germany , included 3107 diabetes-free persons aged 31 - 81 years at baseline in 1997 - 2001 . 2475 persons participated at 5-year follow-up and gave self-reports of incident diabetes . For the total sample and for subjects aged ≥50 years , statistical properties of prediction models with and without r and om glucose were compared . RESULTS A basic model ( including age , sex , diabetes of parents , hypertension and waist circumference ) and a comprehensive model ( additionally including various lifestyle variables and blood parameters , but not HbA1c ) performed statistically significantly better after adding r and om glucose ( e.g. , the area under the receiver-operating curve ( AROC ) increased from 0.824 to 0.856 after adding r and om glucose to the comprehensive model in the total sample ) . Likewise , adding r and om glucose to prediction models which included HbA1c led to significant improvements of predictive ability ( e.g. , for subjects ≥50 years , AROC increased from 0.824 to 0.849 after adding r and om glucose to the comprehensive model+HbA1c ) . CONCLUSIONS R and om glucose is useful for individual diabetes prediction , and improves prediction models including HbA1c In a prospect i ve study of South African Indians with impaired glucose tolerance ( IGT ) , the serum insulin response during a 75 g oral glucose tolerance test ( OGTT ) was examined in 128 subjects who were classified as IGT 1 year previously ( year 0 ) and in 60 matched control subjects . Based on the results at year 1 , study subjects were divided into three groups , using World Health Organization criteria for glucose tolerance : IGT ( n = 47 ) , diabetes ( n = 41 ) , and transient IGT ( normal glucose tolerance ) ( n = 40 ) . When compared with the control group , despite higher plasma glucose concentrations , the IGT group showed similar fasting insulin , but lower 30-min insulin response ( 57.4 + /- 1.9 mUl-1 vs 86.5 + /- 1.8 , p < 0.001 ) and lower 30-min insulin/glucose ratio ( 7.4 + /- 5.2 vs 13.3 + /- 8.7 , p < 0.001 ) . The insulinogenic index was lower in the IGT group than in the control group at 30 , 60 , 90 , and 120 min ( p < 0.01 , p < 0.001 , p < 0.001 , p < 0.001 , respectively ) . The 2-h insulin response was higher in the IGT group ( 106.7 + /- 1.9 mUl-1 vs 59.2 + /- 1.9 , p < 0.01 ) . The IGT group displayed a delayed pattern of insulin response with maximum levels only at 2-h . Insulin area was similar in the two groups . In the transient IGT group , despite similar plasma glucose levels , the insulin responses at 0 , 15 , 30 , and 60 min ( p < 0.01 , p < 0.001 , p < 0.001 , p < 0.001 , respectively ) were lower than in the control group ; the 30-min insulin/glucose ratio ( 7.1 + /- 5.1 vs 13.3 + /- 8.7 , p < 0.001 ) and 60-min insulinogenic index ( 46.9 + /- 86.3 vs 123.4 + /- 206.3 , p < 0.001 ) were also lower in the transient IGT group . ( ABSTRACT TRUNCATED AT 250 WORDS Purpose : Although there are approximately 200 million people of Malay ethnicity living in Asia , the burden and risk factors of blinding eye diseases in this ethnic group are unknown . This study summarizes the rationale and study design of a population -based study of eye diseases among adult Malays in Singapore . Methods : A population -based cross-sectional study of Malays was design ed in Singapore . The sampling frame consisted of all Malays aged 40–79 living in design ated study areas in southwestern Singapore . From a list of 16,069 names provided by the Ministry of Home Affairs , age-stratified r and om sampling was used to select 5,600 names ( 1,400 people from each decade of 40–49 , 50–59 , 60–69 , and 70–79 years ) . The target sample size for this study was 3,150 persons . Selected individuals were invited to a central ized clinic by letters , telephone calls , and home visits . Participants underwent st and ardized interview and assessment of blood pressure , anthropometry , presenting and best-corrected visual acuity , subjective refraction , ocular biometry , Goldmann tonometry , slit-lamp biomicroscopy , optic disc imaging , digital lens , and retinal photography . Blood and urine sample s were collected for biochemical analyses and further stored for future studies . Selected participants also had gonioscopic examination , visual fields test , and assessment of ankle and brachial blood pressure to detect presence of peripheral vascular disease . Conclusions : This study provides population -based data on the prevalence of and risk factors for age-related eye diseases in people of Malay ethnicity in Singapore . Data from this study allow further underst and ing of the etiology and impact of eye diseases in this ethnic group OBJECTIVE In 1997 , the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association ( ADA ) recommended three new sets of criteria for the diagnosis of diabetes that were different from those established by the World Health Organization ( WHO ) in 1985 . One of these three methods was based on a fasting plasma glucose value only . This article compares ADA criteria with WHO criteria by applying them to three subgroups of American Indians in the Strong Heart Study who had no known diabetes . RESEARCH DESIGN AND METHODS The Strong Heart Study is a prospect i ve epidemiological study of vascular disease in three American Indian population s aged 45 - 74 years . During the baseline examination from 1988 to 1991 , participants without diagnosed diabetes underwent a fasting glucose test and a 2-h oral glucose tolerance test . These values were used to compare the ADA and WHO diagnostic criteria . RESULTS By using fasting and 2-h glucose values , prevalence rates of undiagnosed diabetes were 15.9 % according to WHO criteria and 14.4 % according to ADA criteria . The overall agreement rate was 65 % , and the weighted kappa statistic was 0.474 , which indicates moderate agreement . The age-specific analysis showed that , among participants between 45 and 54 years of age , the prevalence rates of undiagnosed diabetes were 13.4 % according to WHO criteria and 12.7 % according to ADA criteria . Among those aged 55 - 74 years , the rates were 18.7 % according to WHO criteria and 16.3 % according to ADA criteria . Thus , the difference in the prevalence rates when using WHO and ADA criteria , although generally small in this population , was three times higher in the older group ( 2.4 % ) than the difference in the younger group ( 0.7 % ) . CONCLUSIONS The Strong Heart Study found that prevalence rates of undiagnosed diabetes determined by ADA criteria and WHO criteria were similar in its American Indian population . The data suggest that the difference between the two criteria may increase as age increases . Longitudinal data will be needed to evaluate further the utility of the two criteria OBJECTIVE To describe the change in diabetic status over 30 months . RESEARCH DESIGN AND METHODS Cohort study of 5,400 Caucasian men from the Paris Prospect i ve Study , aged 44 - 55 years , who were not known as having diabetes at baseline . Oral glucose tolerance tests were performed at baseline and after 30 months . RESULTS At baseline , diabetes was diagnosed in 2.9 % of the men by fasting plasma glucose ( FPG ) > or = 7.0 mmol/l and in 0.9 % by isolated postchallenge hyperglycemia ( IPH ) ( FPG < 7.0 mmol/l and 2-h plasma glucose concentration > or = 11.1 mmol/l ) , i.e. , one in four of all men with newly diagnosed diabetes . Thirty months later , 42 % of the men with diabetes diagnosed by FPG reverted to nondiabetic status , compared with 72 % of those with diabetes diagnosed by IPH ( P < 0.0001 ) . For the men with diabetes diagnosed by FPG at baseline , diabetes had been diagnosed by a physician at 30 months in 11.5 % , in contrast to only 3.9 % of those with diabetes diagnosed by IPH ( P < 0.05 ) . For the 51 men with diabetes diagnosed by IPH at baseline , those who reverted to nondiabetic status had a lower frequency of family history of diabetes ( P < 0.1 ) , a higher mean corpuscular volume ( P < 0.08 ) , and a significantly higher total cholesterol concentration ( P < 0.006 ) at baseline ; in contrast , for the 156 men with diabetes diagnosed by FPG at baseline , the men who reverted to nondiabetic status and those who remained diabetic had similar characteristics . CONCLUSIONS In this epidemiological study , diabetes diagnosed by one FPG concentration was more stable than diabetes diagnosed by one IPH ; in clinical practice , the diagnosis of diabetes requires confirmation of the hyperglycemia Abstract BACKGROUND : There is controversy surrounding the issue of whether , and how , to screen adults for type 2 diabetes . Our objective was to measure the incidence of new diabetes among out patients enrolled in a health care system , and to determine whether hemoglobin A1c ( HbA1c ) values would allow risk stratification for patients ’ likelihood of developing diabetes over 3 years . METHODS : We conducted a prospect i ve cohort study with 3-year follow-up at a single large , tertiary care , Department of Veterans Affairs Medical Center ( VAMC ) . A convenience sample of 1,253 out patients without diabetes , age 45 to 64 , with a scheduled visit at the VAMC , were screened for diabetes using an initial HbA1c measurement . All subjects with HbA1c ≥6.0 % ( normal , 4.0 % to 6.0 % ) were invited for follow-up fasting plasma glucose ( FPG ) . We then surveyed patients annually for 3 years to ascertain interval diagnosis of diabetes by a physician . The baseline screening process was repeated 3 years after initial screening . After the baseline screening , new cases of diabetes were defined as either the self-report of a physician ’s diagnosis of diabetes , or by HbA1c ≥7.0 % or FPG ≥7.0 mmol/L at 3-year follow-up . The incidence of diabetes was calculated as the number of new cases per person-year of follow-up . RESULTS : One thous and two hundred fifty-three patients were screened initially , and 56 ( 4.5 % ) were found to have prevalent unrecognized diabetes at baseline . The 1,197 patients without diabetes at baseline accrued 3,257 person-years of follow-up . There were 73 new cases of diabetes over 3 years of follow-up , with an annual incidence of 2.2 % ( 95 % confidence interval [ CI ] , 1.7 % to 2.7 % ) . In a multivariable logistic regression model , baseline HbA1c and baseline body mass index ( BMI ) were the only significant predictors of new onset diabetes , with HbA1c having a greater effect than BMI . The annual incidence of diabetes for patients with baseline HbA1c ≤ 5.5 was 0.8 % ( CI , 0.4 % to 1.2 % ) ; for HbA1c 5.6 to 6.0 , 2.5 % ( CI , 1.6 % to 3.5 % ) ; and for HbA1c 6.1 to 6.9 , 7.8 % ( CI , 5.2 % to 10.4 % ) . Obese patients with HbA1c 5.6 to 6.0 had an annual incidence of diabetes of 4.1 % ( CI , 2.2 % to 6.0 % ) . CONCLUSIONS : HbA1c testing helps predict the likelihood that patients will develop diabetes in the future . Patients with normal HbA1c have a low incidence of diabetes and may not require rescreening in 3 years . However , patients with elevated HbA1c who do not have diabetes may need more careful follow-up and possibly aggressive treatment to reduce the risk of diabetes . Patients with high-normal HbA1c may require follow-up sooner than 3 years , especially if they are significantly overweight or obese . This predictive value suggests that HbA1c may be a useful test for periodic diabetes screening In 2003 , the American Diabetes Association reduced the lower limit defining impaired fasting glucose ( IFG ) to 100 mg/dL. The aim of this study was to analyze the impact of this change in the definition of IFG in a low-risk white population from northern Spain . The Asturias Study is a prospect i ve , population -based survey of diabetes and cardiovascular risk factors . The baseline examination was carried out between 1998 and 1999 when 1034 individuals ( age range , 30 - 75 years ) were r and omly selected to determine the prevalence of type 2 diabetes mellitus and prediabetes in the Principality of Asturias ( northern Spain ) . In 2004 to 2005 , these same subjects were invited for a follow-up examination . All participants without known diabetes underwent an oral glucose tolerance test both at baseline and follow-up . Application of the new American Diabetes Association definition result ed in 3 times more persons having IFG . The incidence rates of diabetes were 3.8 , 19.5 , and 58.0 per 1000 person-years in subjects with initial FPG values < 100 , 100 to 109 , and 110 to 125 mg/dL , respectively . Inclusion of persons with an intermediate risk in the 100- to 109-mg/dL zone to the definition of IFG changed its positive predictive value , specificity , and sensitivity to predict diabetes from 36.5 % , 94.5 % , and 43.2 % to 19.9 % , 77.3 % , and 75 % , respectively . Receiver operating characteristics curve analysis including all the baseline fasting plasma glucose levels from 64 to 125 mg/dL depending on their ability to predict diabetes showed that the point closest to the ideal of 100 % sensitivity and 100 % specificity was 100 mg/dL. In conclusion , this study indicated that lowering the cutoff point for IFG optimizes its ability to predict diabetes in this Spanish population . The addition of other risk factors such as impaired glucose tolerance , hypertriglyceridemia , and overweight to IFG can stratify diabetes risk better The Australian Diabetes , Obesity and Lifestyle Study ( AusDiab ) addresses the urgent need for data on diabetes prevalence , risk factors and associated conditions in Australia . Here we describe the methods used and the response rates obtained . AusDiab was a population -based cross-sectional survey of national diabetes mellitus prevalence and associated risk factors in people aged > or = 25 years , conducted between May 1999 and December 2000 in the six states and the Northern Territory of Australia . The study involved an initial household interview , followed by a biomedical examination that included an oral glucose tolerance test ( OGTT ) , st and ard anthropometric tests , blood pressure measurements and the administration of question naires . Of the 20347 eligible people ( aged > or = 25 years and resident at the address for > or = 6 months ) who completed a household interview , 11247 ( 55.3 % ) attended for the biomedical examination . Of those who completed the biomedical examination 55.1 % were female . Comparisons with the 1998 Australian population estimates showed that younger age responders were under-represented at the biomedical examination , while the middle-aged and older age groups were over-represented . Weighting of the AusDiab data for age and gender have corrected for this bias . AusDiab , which is the largest national diabetes prevalence study undertaken in a developed nation to have used an OGTT , provides a valuable national re source for the study of the prevalence and possible causes of diabetes , as well as identifying possible risk factors that may lead to diabetes . Furthermore , it generates the baseline data for a prospect i ve 5-year cohort study . The data will be important for national and regional public health and lifestyle education and health promotion programs AIMS We assessed whether the increased sequential changes in the fasting plasma glucose level ( FPG ) that is still within the normoglycemic range could be a predictor for future diabetes . METHODS A prospect i ve cohort study was conducted with 5296 male employees , aged 31 - 44 years . A sequential change in the FPG level was defined as the first follow-up FPG level minus the baseline FPG level . The incident diabetes was assessed at annual examinations during the next 4.1 years . Cox proportional hazard analyses were performed . RESULTS During the 21,575.5 person-years follow-up among the 5,296 subjects , a total of 156 incident cases of type 2 diabetes occurred ( 116 cases among the 4,975 normoglycemic subjects and 40 cases among the 321 subjects with impaired fasting glucose ) . An increase in the FPG level from the baseline to the first follow-up , although still within the normoglycemic range ( FPG<100 mg/dl ) , significantly predicted future diabetes : the multivariate hazard ratios associated with the sequential changes in the FPG of < -3 , -3 to 3 , 4 - 6 , 7 - 9 , and > 9 mg/dl were 0.75 , 1.00 ( reference ) , 2.28 , 3.28 , and 6.10 , respectively ( p for trend < 0.001 ) . CONCLUSIONS The increase of the sequential changes in the FPG level that were within the normal glucose range was associated with a higher risk for developing diabetes . Thus , conducting assessment for the serial changes in the FPG level may help to identify the young , healthy , normoglycemic individuals at risk for type 2 diabetes BACKGROUND Identification of the population at high risk of developing atherosclerotic cardiovascular disease ( ASCVD ) is critical for its prevention . The aim of the present study was to evaluate the use of fasting blood glucose ( FBG ) to predict ASCVD . METHODS In all , 18 610 participants , aged 35 - 74 years at enrollment , were included in this prospect i ve study . Baseline information was collected using a st and ardized question naire , physical examinations , and laboratory tests . During follow-up , disease status and vital information were up date d. Cox proportional hazards regression analysis was used to estimate associations , with normal FBG ( 70 - 99 mg/dL ) as the reference group . Anthropometric measurements , socioeconomic status , and conventional cardiovascular risk factors were included in the multivariate-adjusted model . RESULTS After 7.8 years follow-up ( 145 223 person-years ) , there were 519 cases of ASCVD . The multivariate-adjusted hazard ratios ( HR ) , with 95 % confidence intervals ( CI ) , for ASCVD in patients with low FBG ( < 70 mg/dL ) , impaired fasting glucose ( IFG ; 100 - 125 mg/dL ) , and diabetes ( ≥126 mg/dL , use of antidiabetic medication and /or self-report ) were 1.35 ( 0.84 , 2.15 ) , 1.02 ( 0.81 , 1.27 ) , and 1.68 ( 1.26 , 2.23 ) , respectively . Although IFG was associated with the development of diabetes ( multivariate-adjusted HR 3.67 ; 95 % CI 3.20 , 4.21 ) , it was only associated with incident ASCVD in the univariate model ( HR 1.52 ; 95 % CI 1.23 , 1.88 ) . The association of diabetes with coronary heart disease was more pronounced than that with stroke . Gender and residential differences were also identified . CONCLUSIONS In the present study , IFG was associated with the development of diabetes but not incident ASCVD . Prevention strategies to reduce the development of diabetes in people with IFG are critical to improve cardiovascular health Previous epidemiological studies have shown that vigorous physical activity reduces the development of type 2 diabetes ( 1–3 ) . A recommendation from the Centers for Disease Control and Prevention reported that individuals should engage in ≥30 min of moderate-intensity physical activity , such as brisk walking , on most days of the week for health promotion and disease prevention ( 4 ) ; however , it is unclear whether mild physical activity ( i.e. , walking to walk ) reduces the risk for type 2 diabetes . In the present study , we examined the relationship between walking to work and the development of type 2 diabetes during a 4-year observational period . The Kansai Healthcare Study is an ongoing cohort investigation design ed to clarify the risk factors for cardiometabolic diseases . Between April 2000 and March 2001 , 12,647 male employees of a company in the area of Kansai , Japan , who were aged 40–55 years at entry and considered to be involved in sedentary jobs were enrolled in this study . All employees aged ≥40 years underwent annual detailed medical check-ups . The protocol for this research was review ed by the Human Subjects Review Committee at Osaka City University . For current analysis , study participants consisted of 11,073 Japanese men aged 40–55 years at entry with a fasting plasma glucose ( FPG ) < 126 mg/dl and not taking oral hypoglycemic medication or insulin . A 4-year follow-up examination after baseline was conducted between April 2004 and March 2005 . We excluded 53 men because of death and 2,016 men because of OBJECTIVE To examine prospect ively the association between age , BMI , and subsequent incidence of type 2 diabetes in Australian aboriginal people . RESEARCH DESIGN AND METHODS We performed a stratified analysis of incidence data from a community-based longitudinal study . Measures included fasting and 2-h postload glucose concentrations , and BMI , stratified into four categories . Subjects were 882 male and female participants in diabetes screening initiatives in two remote Australian aboriginal communities , free from diabetes at baseline , ages 15 - 77 years . RESULTS There were 46 incident cases of diabetes over 2,808 person-years of follow-up . BMI modified strongly the sex- and community-adjusted association between age and diabetes incidence ( P < 0.001 ) . Adjusted for age , sex , and community , the population diabetes incidence rate was 20.3 cases/1,000 person-years , with BMI -specific rates of 10.7 - 47.2 cases/1,000 person-years , and relative risks ( 95 % CI ) for BMI strata beyond the reference category ( < 25 kg/m2 ) of 3.3 ( 1.5 - 7.0 ) , 2.7 ( 1.1 - 6.8 ) , and 4.4 ( 1.7 - 11.6 ) , respectively . The population 's attributable risk ( 95 % CI ) associated with BMI beyond the reference category was 70.1 % ( 58.1 - 82.4 ) . CONCLUSIONS BMI -specific diabetes incidence rates in Australian aboriginal people are among the highest in the world . Diabetes incidence in the lowest BMI category ( 10.7 cases/1,000 person-years ) is two to five times greater than corresponding rates for non-aboriginal population s. An urgent need exists to prevent weight gain associated with diabetes . Further study is required to determine for aboriginal people an optimal range of BMI , likely lower than that suggested for non-aboriginal population Incidence rates and risk factors for type 2 diabetes in low-risk population s are not well documented . We investigated these in white individuals who were aged 40 - 79 years and from the population of Bruneck , Italy . Of an age- and sex-stratified r and om sample of 1,000 individuals who were identified in 1990 , 919 underwent an oral glucose tolerance test ( OGTT ) and an assessment of physiological risk factors for diabetes , including insulin resistance ( homeostasis model assessment , HOMA-IR ) , and postchallenge insulin response ( Sluiter 's Index ) . Diabetes at baseline by fasting or 2-h OGTT plasma glucose ( World Health Organization criteria , n = 82 ) was excluded , leaving 837 individuals who were followed for 10 years . Incident cases of diabetes were ascertained by confirmed diabetes treatment or a fasting glucose > or=7.0 mmol/l . At follow-up , 64 individuals had developed diabetes , corresponding to a population -st and ardized incidence rate of 7.6 per 1,000 person-years . Sex- and age-adjusted incidence rates were elevated 11-fold in individuals with impaired fasting glucose at baseline , 4-fold in those with impaired glucose tolerance , 3-fold in overweight individuals , 10-fold in obese individuals , and approximately 2-fold in individuals with dyslipidemia or hypertension . Incidence rates increased with increasing HOMA-IR and decreasing Sluiter 's Index . As compared with normal insulin sensitivity and normal insulin response , individuals with low insulin sensitivity and low insulin response had a sevenfold higher risk of diabetes . Baseline impaired fasting glucose , BMI , HOMA-IR , and Sluiter 's Index were the only independent predictors of incident diabetes in multivariate analyses . We conclude that approximately 1 % of European white individuals aged 40 - 79 years develop type 2 diabetes annually and that " subdiabetic " hyperglycemia , obesity , insulin resistance , and impaired insulin response to glucose are independent predictors of diabetes BACKGROUND Hemoglobin A1c ( HbA1c ) is a marker of cumulative glycemic exposure over the preceding 2- to 3-month period . Whether mild elevations of this biomarker provide prognostic information for development of clinical ly evident type 2 diabetes and cardiovascular disease among individuals at usual risk for these disorders is uncertain . METHODS We examined baseline HbA1c levels as a predictor of incident clinical diabetes and cardiovascular disease ( nonfatal myocardial infa rct ion , coronary revascularization procedure , ischemic stroke , or death from cardiovascular causes ) in a prospect i ve cohort study beginning in 1992 of 26,563 US female health professionals aged 45 years or more without diagnosed diabetes or vascular disease ( median follow-up 10.1 years ) . RESULTS During follow-up , 1238 cases of diabetes and 684 cardiovascular events occurred . In age-adjusted analyses using quintiles of HbA1c , a risk gradient was observed for both incident diabetes and cardiovascular disease . After multivariable adjustment , HbA1c remained a strong predictor of diabetes but was no longer significantly associated with incident cardiovascular disease . In analyses of threshold effects , adjusted relative risks for incident diabetes in HbA1c categories of less than 5.0 % , 5.0 % to 5.4 % , 5.5 % to 5.9 % , 6.0 % to 6.4 % , 6.5 % to 6.9 % , and 7.0 % or more were 1.0 , 2.9 , 12.1 , 29.3 , 28.2 , and 81.2 , respectively . Risk associations persisted after additional adjustment for C-reactive protein and after excluding individuals developing diabetes within 2 and 5 years of follow-up . CONCLUSIONS These prospect i ve findings suggest that HbA1c levels are elevated well in advance of the clinical development of type 2 diabetes , supporting recent recommendations for lowering of diagnostic thresholds for glucose metabolic disorders . In contrast , the association of HbA1c with incident cardiovascular events is modest and largely attributable to coexistent traditional risk factors The potential role of physical activity in the primary prevention of non-insulin-dependent diabetes mellitus ( NIDDM ) is largely unknown . We examined the association between regular vigorous exercise and the subsequent incidence of NIDDM in a prospect i ve cohort of 87,253 US women aged 34 - 59 years and free of diagnosed diabetes , cardiovascular disease , and cancer in 1980 . During 8 years of follow-up , we confirmed 1303 cases of NIDDM . Women who engaged in vigorous exercise at least once per week had an age-adjusted relative risk ( RR ) of NIDDM of 0.67 ( p less than 0.0001 ) compared with women who did not exercise weekly . After adjustment for body-mass index , the reduction in risk was attenuated but remained statistically significant ( RR = 0.84 , p = 0.005 ) . When analysis was restricted to the first 2 years after ascertainment of physical activity level and to symptomatic NIDDM as the outcome , age-adjusted RR of those who exercised was 0.5 , and age and body-mass index adjusted RR was 0.69 . Among women who exercised at least once per week , there was no clear dose-response gradient according to frequency of exercise . Family history of diabetes did not modify the effect of exercise , and risk reduction with exercise was evident among both obese and nonobese women . Multivariate adjustments for age , body-mass index , family history of diabetes , and other variables did not alter the reduced risk found with exercise . Our results indicate that physical activity may be a promising approach to the primary prevention of NIDDM Several investigators have observed an association between alcohol consumption and elevated glucose levels , raising the possibility that alcohol may increase the risk of diabetes . This hypothesis was evaluated prospect ively among 85,051 women participating in the Nurses ' Health Study who were 34 to 59 years of age in 1980 and had no history of cancer , coronary heart disease , or diabetes . At baseline , participants completed an independently vali date d dietary question naire which included information on the consumption of beer , wine , and liquor . Incident cases of non-insulin-dependent diabetes were reported on follow-up question naires sent in 1982 and 1984 ( 98 % response to at least one follow-up ) ; 526 cases were confirmed by a supplementary question naire regarding symptoms , laboratory values , and treatment . The risk of diabetes decreased monotonically with increasing alcohol consumption ( chi trend = -9.4 , p less than 0.0001 ) . Compared with nondrinkers , women consuming 5 - 14.9 g of alcohol per day ( about 4 - 10 drinks per week ) had an age-adjusted relative risk of diabetes of 0.4 ( 95 % confidence interval ( CI ) 0.3 - 0.6 ) ; for 15 g or more per day , the relative risk was 0.3 ( 95 % CI 0.2 - 0.4 ) . However , a strong inverse association between alcohol drinking and body weight explained much of the apparent protective effect of alcohol . After simultaneous adjustment for Quetelet index ( weight (kg)/height (m)2 ) , family history of diabetes , total caloric intake , and age , the relative risk of diabetes for consumers of 5 - 14.9 g per day was 0.8 ( 95 % CI 0.6 - 1.2 ) , and for women who drank 15 + g per day , the relative risk was 0.6 ( 95 % CI 0.3 - 0.9 ) . These data provide no support for the hypothesis that moderate alcohol intake increases the risk of non-insulin-dependent diabetes To determine the optimal fasting plasma glucose ( FPG ) cut-off value which effectively identifies high risk subjects for type 2 diabetes in Japanese , we conducted a population -based prospect i ve study on diabetes as part of the Japan Public Health Center-based Prospect i ve Study and estimated the 5-year incidence of diabetes . The subjects of the analysis of this study were 2,207 Japanese aged 51 - 70 at baseline from whom a fasting blood sample was collected in both the baseline and the 5-year follow-up surveys and who completed the question naires at both times . Diabetes was defined as an FPG value > or = 126 mg/dL ( 7.0 mmol/L ) and /or self-reported diabetes . A total of 125 subjects developed diabetes during the 5 years after the baseline survey , and the incidence rate for a baseline FPG value of 95 - 99 , 100 - 104 , 105 - 109 , 110 - 114 , 115- 119 , and 120 - 125 mg/dL was 6.1 , 11.5 , 30.3 , 52.6 , 86.4 , and 115.2 per 1,000 person-years , respectively . The results of receiver operating characteristic curve analysis suggested that an FPG value of 102 mg/dL ( 5.67 mmol/L ) was optimal for predicting diabetes during the next 5-years . The cut-off value was similar in both genders and in the 51- to 60-year-old group and 61- to 70-year-old group . Use of hemoglobin A(1c ) level > or = 6.1 % for an additional diagnostic criterion result ed in a small increment in incidence , but the cut-off value for predicting diabetes was almost the same ( 101 mg/dL ) . The results of this study suggested that the cut-off FPG value should be lowered in terms of prediction of type 2 diabetes among Japanese population AIM Experimental evidence suggests that osteocalcin is a key messenger that affects both adipocytes and insulin-producing β cells . Epidemiological cross-sectional studies have shown a negative association between plasma levels of osteocalcin and glucose . For this reason , the hypothesis that lower baseline osteocalcin plasma levels are associated with diabetes was prospect ively tested . METHODS The study population consisted of individuals at high risk for type 2 diabetes who were screened for participation in the Greek arm of a European type 2 diabetes prevention study ( the DE-PLAN study ) . All participants were free of diabetes at baseline and underwent a second evaluation 3 years later . Diabetes status was defined according to an oral glucose tolerance test . RESULTS A total of 307 subjects were included in the present analysis . The population , including 154 men ( 50.3 % ) , was middle-aged ( 54.4 ± 10.2 years ) and overweight ( BMI : 29.5 ± 4.9 kg/m(2 ) ) . At baseline , mean total plasma osteocalcin was lower in those with impaired fasting glucose and /or impaired glucose tolerance compared with those with normal glucose tolerance ( 6.0 ± 3.1 ng/mL vs. 7.3 ± 4.0 ng/mL , respectively ; P = 0.01 ) . After 3 years , 36 subjects had developed diabetes . In the prospect i ve evaluation , there was no association between baseline osteocalcin levels and diabetes ( OR : 1.04 per 1 ng/mL , 95 % CI : 0.93 - 1.15 ; P = 0.49 ) on multivariable logistic regression analysis , nor was there any correlation with changes in plasma glucose after 3 years ( r = 0.09 , P = 0.38 ) . CONCLUSION Our prospect i ve results show that lower levels of circulating osteocalcin do not predict future diabetes development and , in contrast to most cross-sectional published data so far , suggest that this molecule may not be playing a major role in glucose homoeostasis in humans AIMS To determine the incidence of Type 2 diabetes in an elderly population in Germany and its association with clinical and lifestyle factors . METHODS Oral glucose tolerance tests ( OGTT , World Health Organization criteria ) were carried out in a r and om sample of 1353 subjects ( age group 55 - 74 years ; 62 % response ) in Augsburg ( Southern Germany ) ( 1999 - 2001 ) . The cohort was re-investigated in 2006 - 2008 . Of those individuals without diabetes ( baseline ) , 887 ( 74 % ) participated in the follow-up . RESULTS Ninety-three ( 10.5 % ) developed diabetes during the 7-year follow-up period { st and ardized incidence rates [ 95 % confidence interval ( CI ) ] per 1000 person-years : total 15.5 ; 12.6 , 19.1 ; men 20.2 ; 15.6 , 26.1 ; women 11.3 ; 7.9 , 16.1}. In both sexes , those who developed diabetes were slightly older , were more obese , had a more adverse metabolic profile ( higher glucose values , HbA(1c ) , fasting insulin , uric acid , and triglycerides ) and were more likely to have hypertension at baseline than were participants remaining free of diabetes ( P < 0.05 ) . On stepwise logistic regression , age , parental diabetes , body mass index , uric acid , current smoking , HbA(1c ) and fasting and 2-h glucose ( OGTT ) were strong predictors of diabetes incidence . The risk of diabetes was higher in subjects with isolated impaired glucose tolerance ( odds ratio 8.8 ; 95 % CI 5.0 , 15.6 ) than in isolated impaired fasting glucose ( 4.7 ; 2.2 , 10.0 ) , although the difference did not reach statistical significance . CONCLUSIONS For the first time , we have estimated the incidence of Type 2 diabetes in an elderly German cohort and demonstrated that it is among the highest in Europe . The OGTT appears to be useful in identifying individuals with high Type 2 diabetes risk . Our results support a role of smoking in the progression to diabetes A four-yr prospect i ve study was undertaken to examine the natural history of IGT in 128 South-African Indians classified as such at year 0 of the study , based on WHO criteria . Subjects were reexamined at year 1 and year 4 . Of the 113 subjects who completed the study , 50.4 % progressed to NIDDM ( rate of progression 12.6%/yr ) , 24.8 % persisted with IGT , and 24.8 % , reverted to NGT . The majority ( 72 % ) who progressed to NIDDM did so in year 1 . At year 1 , 47 subjects were still classified as IGT ; of the 40 subjects completing the study , 16 subjects ( 40 % ) progressed to NIDDM , 17 subjects ( 42.5 % ) persisted with IGT , and 7 subjects ( 17.5 % ) reverted to NGT . Examination of risk factors predictive of subsequent progression to NIDDM was undertaken by analysis of baseline variables in two ways : When year 0 was used as baseline ( in 113 IGT0 subjects ) , significant predictive risk factors were the FPG and 2-h plasma glucose concentrations . All subjects who at year 0 had 2-h plasma glucose ≥ 10.2 and < 11.1 mM or FPG ≥ 7.3 but < 7.8 mM , subsequently progressed to NIDDM . When year 1 was used as baseline ( 40 IGT1 subjects ) , 90-min plasma glucose concentration ( midtest level ) was found to be a significant risk factor for development of NIDDM . In conclusion , this study has demonstrated that in South-African Indians with IGT , the majority ( 50.4 % ) progress to NIDDM within 4 yr ; significant predictors of subsequent diabetes are the baseline fasting and 2-h plasma glucose concentration . The midtest plasma glucose also may be a useful predictor of clinical outcome . Moreover , the study highlighted the rapid decompensation to NIDDM in the first year and the demonstration of cut-off levels of plasma glucose above which the risk of development of NIDDM is total BACKGROUND A prospect i ve evaluation of the relationship between insulin secretion and insulin sensitivity , derived from the fasting state , is needed in clinical practice in order to identify the worsening of glucose metabolism . In this study the authors examine whether the product of insulin sensitivity and insulin secretion , assessed from the fasting state , predicts progression from normal glucose tolerance ( NGT ) to impaired fasting glucose ( IFG ) and from impaired glucose tolerance ( IGT ) to type 2 diabetes mellitus ( T2DM ) . MATERIAL S AND METHODS A cohort of 300 subjects with NGT and 75 subjects with IGT were followed up over a 5-year period . Insulin sensitivity was calculated using the Belfiore index ( B ) and insulin secretion by the homeostasis model analysis beta-cell ( HOMA-beta cell ) index : the product of B-beta is expressed as : ( 40 x Ins(0 ) pmol L(-1))/Glu(0 ) mmol L(-1){[(Glu(0 ) mmol L(-1)x Ins(0 ) pmol L(-1 ) ) + 1 ] - 3.5[(Glu(0 ) mmol L(-1 ) x Ins(0 ) pmol L(-1 ) ) - 1 ] } , where Glu(0 ) is fasting glucose and Ins(0 ) is fasting insulin . RESULTS From baseline at the end of the follow-up period , the product B-beta decreased 10.7 % and 52.2 % in progressors to IGT and T2DM , respectively . The product B-beta predicts the progression from NGT to IGT [ relative risk ( RR ) 2.7 , CI(95 % ) 1.2 - 9.1 ] and from IGT to T2DM ( RR 5.3 , CI(95 % ) 1.3 - 8.55 ) . The cut-off point for the product B-beta that better predicts progression from NGT to IGT is 0.25 ( sensitivity 88 % , specificity 92 % ) and from IGT to T2DM 0.15 ( sensitivity 92 % , specificity 95 % ) . CONCLUSIONS Adaptation of insulin secretion to compensate for decreased insulin sensitivity during transition to IGT and T2DM can be successfully assessed with simple measures derived from the fasting state . The product B-beta predicts the development to IGT and T2DM OBJECTIVE To evaluate the significance of transient impaired glucose tolerance ( IGT ) in terms of the risk of progression to NIDDM and the serum insulin response during oral glucose tolerance test ( OGTT ) in a prospect i ve study on the natural history of IGT in South African Indians . RESEARCH DESIGN AND METHODS This is a report on 87 subjects who formed part of a 4-year prospect i ve study in 128 subjects classified with IGT at baseline ( year 0 ) using World Health Organization criteria for glucose tolerance . Subjects were reexamined at years 1 and 4 . At year 1 , based on OGTT results , the subjects were divided into three groups : transient IGT ( normal glucose tolerance [ trIGT ] , n = 40 ) , persistent IGT ( pIGT , n = 47 ) , and diabetes ( n = 41 ) . Analysis was performed on the 87 subjects who were classified as IGT at year 0 , but who had not progressed to NIDDM by year 1 of the study At baseline ( year 0 ) , a modified OGTT was performed ; between years 1 and 4 , the OGTT included timed midtest sample s for plasma glucose and serum insulin . Analysis of predictive factors for progression to diabetes or reversion to normal glucose tolerance was undertaken using year 0 as baseline . RESULTS By year 4 , 72 subjects ( 82.8 % ) completed the study Of the 32 subjects in the trIGT group , none ( 0 % ) had progressed to NIDDM , 11 ( 34.4 % ) had reverted to IGT ( N-IGT ) , and 21 ( 65.6 % ) had persisted with normal glucose tolerance ( N-N ) ; of the 40 subjects in the pIGT group , 16 ( 40 % ) had progressed to NIDDM ( IGT-D ) , 17 ( 42.5 % ) had persisted with IGT ( IGT-IGT ) , and 7 ( 17.5 % ) had reverted to normal glucose tolerance ( IGT-N ) . Significant predictive factors for reversion to normal glucose tolerance included absence of obesity ( P = 0.0131 , odds ratio [ OR ] 4.2 , 95 % CI 1.4–13.1 ) and 2-h plasma glucose level ( P = 0.027 , OR 2.4 , 95 % CI 1.11–5.13 ) at baseline ( year 0 ) . Intergroup ( cross-sectional ) analysis showed that the serum insulin response was higher in the pIGT than in the trIGT subgroup ( fasting serum insulin : IGT-N vs. N-IGT and N-N , 16.9 ± 1.9 vs. 6.8 ± 2.1 and 6.1 ± 2.4 μU/ml , respectively , P < 0.001 ; 2-h postload serum insulin : IGT-IGT vs. N-IGT , 116.8 ± 2.2 vs. 60.3 ± 1.7 μU/ml , P < 0.05 ) . By contrast , the insulinogenic index was higher in the trIGT subgroups both at year 1 ( 90-min : N-N vs. IGT-D , 48.9 ± 3.9 vs. 14.1 ± 2.5 ; P < 0.05 ) and at year 4 ( N-N vs. remaining four subgroups , P < 0.01 at 60 min and 90 min ) . Intragroup ( prospect i ve ) comparisons showed that in the N-IGT subgroup , the mean 2-h insulinogenic index was lower at year 4 than at year 1 ( 19.9 ± 1.7 vs. 66.0 ± 2.7 ; P < 0.05 ) . CONCLUSIONS In this 4-year prospect i ve study in South African Indians , transient IGT carries no risk of progression to NIDDM . The significant predictive factors for reversion to normal glucose tolerance include lower baseline obesity prevalence and 2-h postload plasma glucose level . Moreover , in this group , β-cell secretory function appeared to deteriorate with worsening of glucose tolerance Cardiovascular disease risk factors were measured 10 - 15 years ( mean , 11.9 years ) prior to the diagnosis of impaired glucose tolerance and non-insulin-dependent diabetes mellitus in Rancho Bernardo , California . There were 1,847 men and women aged 40 - 79 years who had no known diabetes or fasting hyperglycemia at baseline ( 1972 - 1974 ) . At the follow-up examination ( 1984 - 1987 ) , 1,115 men and women ( 60.4 % ) had normal glucose tolerance , 513 ( 27.8 % ) had impaired glucose tolerance , and 219 ( 11.9 % ) had non-insulin-dependent diabetes mellitus as defined by World Health Organization criteria . Rates of impaired glucose tolerance and non-insulin-dependent diabetes mellitus increased with age , and impaired glucose tolerance was approximately twice as common as non-insulin-dependent diabetes mellitus . Those with non-insulin-dependent diabetes mellitus were older and more overweight and had higher levels of blood pressure , fasting plasma glucose , and triglyceride at baseline than those whose glucose tolerance remained normal ; those with impaired glucose tolerance generally had intermediate levels of the same risk factors . When it was examined in a prospect i ve fashion , in general , the age-adjusted risk of non-insulin-dependent diabetes mellitus increased with increasing quartile of each risk factor , and the risk of non-insulin-dependent diabetes mellitus in a given quartile was greater than that for impaired glucose tolerance . Logistic regression analyses showed these factors to be positively associated with a subsequent diagnosis of impaired glucose tolerance as well as non-insulin-dependent diabetes mellitus in women , and to a lesser degree in men , independent of baseline age and body mass index ( weight (kg)/height (m)2 ) . These data illustrate that a less favorable cardiovascular risk factor profile precedes the diagnosis of both non-insulin-dependent diabetes mellitus and impaired glucose tolerance The aim of the study was to analyze cardiovascular risk factors as predictors for developing non-insulin-dependent diabetes mellitus ( NIDDM ) in people with impaired glucose tolerance . A cross-sectional survey of glucose tolerance was conducted in people , aged 50 - 74 , who were r and omly selected from the registry of the middle-sized town Hoorn ( The Netherl and s ) . Based on the mean values of two oral glucose tolerance tests , people were classified in glucose tolerance categories according to the WHO criteria . The mean follow-up time was 36 months ( range 13 - 55 months ) . The cumulative incidence of NIDDM was 34 % ( 95 % CI 16.9 - 45.1 ) . In multiple logistic regression analysis , cardiovascular risk factors at baseline did not predict the conversion from impaired glucose tolerance to NIDDM , in contrast with the two-hour plasma glucose level ( odds ratio 3.56 , p < 0.001 ) and the fasting proinsulin level , as one of the determinants of beta-cell dysfunction ( Odds ratio 2.1 , p < 0.05 ) . The baseline HDL-cholesterol level , one of the components of the insulin resistance syndrome , was associated with the conversion from impaired glucose tolerance to normal glucose tolerance ( Odds ratio 1.58 , p < 0.05 ) . The results of our study seem to support the hypothesis that conversion from impaired glucose tolerance to normal glucose tolerance depends on insulin resistance and the development of NIDDM from impaired glucose tolerance depends on beta-cell dysfunction Identification of individuals at high risk of developing type 2 diabetes is a prerequisite for prevention of the disease . We therefore studied risk factors predicting type 2 diabetes in the Botnia Study in Western Finl and . A total of 2,115 nondiabetic individuals were prospect ively followed with repeated oral glucose tolerance tests . After a median follow-up of 6 years , 127 ( 6 % ) subjects developed diabetes . A family history of diabetes ( hazard ratio [ HR ] 2.2 , P = 0.008 ) , BMI ( HR for comparison of values below or above the median 2.1 , P < 0.001 ) , waist-to-height index ( 2.3 , P < 0.001 ) , insulin resistance ( 2.1 , P = 0.0004 ) , and beta-cell function adjusted for insulin resistance ( 2.7 , P < 0.0001 ) predicted diabetes . Marked deterioration in beta-cell function with modest changes in insulin sensitivity was observed during the transition to diabetes . The combination of FPG > or = 5.6 mmol/l , BMI > or = 30 kg/m(2 ) , and family history of diabetes was a strong predictor of diabetes ( 3.7 , P < 0.0001 ) . Of note , using FPG > or = 6.1 mmol/l or 2-h glucose > or = 7.8 mmol/l did not significantly improve prediction of type 2 diabetes . In conclusion , a marked deterioration in beta-cell function precedes the onset of type 2 diabetes . These individuals can be identified early by knowledge of FPG , BMI , and family history of diabetes PURPOSE Little is known about excess risk of incident diabetes conferred by fasting plasma glucose ( FPG ) within the normal range ( < 5.6 mmol/l ) for high risk families . METHODS Healthy 30 - 59 year old non-diabetic siblings ( N = 542 ) of index cases with documented premature coronary disease were followed prospect ively for type 2 diabetes . RESULTS During 8.7+/-3 years of follow-up , incident diabetes was identified in 7.8 % . Rates were incremental with baseline non-diabetes FPG thresholds of 5.0 , 5.6 , 6.1 , and 6.7 mmol/l ( p for trend < 0.0001 ) . FPG was the strongest predictor of incident diabetes even across levels within the normal range . The multivariable adjusted relative risk was 14.9 ( 95 % CI = 3.4 - 65.2 ) at FPG thresholds > or = 5.0 mmol/l versus FPG < 5.0 mmol/l . The maximal diagnostic efficiency for FPG was 5.50 mmol/l ; with sensitivity and specificity 0.782 . All FPG thresholds in the normal range between 5.0 and 5.6 mmol/l showed efficiency levels > 0.74 . The overall area under the ROC curve predicting incident diabetes for normal and prediabetes ranges of FPG was 0.867 . CONCLUSION Higher FPG levels within the design ated " normal " range in high risk families are a potent independent risk factor for type 2 diabetes and may serve as a sentinel to trigger primary preventive interventions The authors hypothesized that increased socioeconomic status and acculturation of Mexican Americans to mainstream US society would be accompanied by a progressive lessening of obesity and non-insulin-dependent diabetes mellitus . This hypothesis was tested in 1979 - 1982 in the San Antonio Heart Study , a population -based study of 1,288 Mexican Americans and 929 non-Hispanic whites , aged 25 - 64 years , r and omly selected from three San Antonio neighborhoods : a low-income barrio , a middle-income transitional neighborhood , and a high-income suburb . Socioeconomic status was assessed by the Duncan Socioeconomic Index , a global measure of socioeconomic status based on occupational prestige . Acculturation was assessed by three scales which measure functional integration with mainstream society , value placed on preserving Mexican cultural origin , and attitude toward traditional family structure and sex-role organization . In Mexican-American men , increased acculturation was accompanied by a statistically significant , linear decline in both obesity and diabetes , while socioeconomic status had no significant effect on either outcome . In Mexican-American women , on the other h and , increased acculturation and increased socioeconomic status were accompanied by statistically significant , linear declines in both outcomes . However , the effects of acculturation on obesity and diabetes prevalence in women were stronger than the effects of socioeconomic status . In women , obesity also appeared to be a more important mediator of the relation between socioeconomic status and diabetes than of the relation between acculturation and diabetes . The results of this study suggest that culturally mediated factors exert a more pervasive influence on obesity and diabetes in Mexican Americans than do socioeconomically mediated factors . The influence of socioeconomic status in women , however , can not be ignored , particularly with regard to obesity BACKGROUND The use of an oral glucose tolerance test ( OGTT ) has been recommended to diagnose type 2 diabetes , but an OGTT with venous blood sampling may not be feasible in the screening phase preceding large epidemiological studies . We have conducted a population -based screening in 2715 men and women and evaluated the diagnostic validity of capillary plasma glucose concentration measurements versus venous plasma glucose concentration measurements in a subset of 350 subjects . METHODS During a single OGTT , glucose concentrations were measured in venous plasma as well as in capillary plasma . RESULTS Based on the 1999 WHO criteria for venous glucose concentrations , the study population ( n=350 ) yielded 97 subjects with type 2 diabetes mellitus , 77 subjects with impaired glucose tolerance and 176 subjects with normal glucose tolerance . Sensitivity and specificity to diagnose type 2 diabetes mellitus by capillary plasma were 84 % and 98 % , respectively . Consistent classification by either venous or capillary plasma glucose measurements was 78 % ( kappa=0.65 , p<0.001 ) . CONCLUSION Capillary glucose measurements are suitable for use in epidemiological studies to diagnose and detect type 2 diabetes and normal glucose tolerance . Use of capillary measurements can result in cost-effective inclusion schemes in epidemiological studies BACKGROUND The Pathobiology of Prediabetes in a Biracial Cohort ( POP-ABC ) study is a prospect i ve evaluation of the natural history impaired glucose regulation . DESIGN AND METHODS The eligibility requirements include age 18 - 65 yr , history of type 2 diabetes in one or both parents , normal fasting plasma glucose ( FPG ) or normal glucose tolerance , and African-American or Caucasian status . Participants underwent assessment s ( including dietary and exercise behavior , clinical examination , glucose tolerance , insulin sensitivity , β-cell function , body composition , energy expenditure ) during 2.25 - 5.5 yr of quarterly follow-up . The primary outcome is the occurrence of prediabetes . Baseline data are presented for the 376 enrolled participants . The cohort was also compared with National Health and Nutrition Examination Survey 2007/2008 participants meeting the age and glycemic criteria for the POP-ABC study . RESULTS The POP-ABC cohort [ mean ( ±SD ) age was 44.2 ± 10.6 yr ] was 57.7 % African-Americans , 42.3 % Caucasians , and 70.7 % females ; 86 % had one parent with diabetes and 14 % had both parents affected . Although greater than 70 % of the cohort were employed and 75 % had more than 13 yr of education , more African-Americans reported incomes less than $ 20,000 and fewer reported incomes more than $ 75,000 compared with Caucasians . Compared with Caucasians , African-Americans had a higher body mass index ( 31.3 ± 7.8 vs. 28.8 ± 7.8 kg/m(2 ) , P = 0.001 ) , a lower FPG ( 90.0 ± 7.72 vs. 92.2 ± 7.60 mg/dl , P = 0.008 ) , higher glycosylated hemoglobin , lower triglycerides , and similar blood pressure , and homeostasis model assessment of insulin resistance , homeostasis model assessment of β-cell function , high-density lipoprotein , and low-density lipoprotein cholesterol levels . Compared with a cross-section of U.S. subjects ( National Health and Nutrition Examination Survey 2007/2008 ) with normal FPG and normal glucose tolerance , participants in the POP-ABC study had similar lipid profile but were more educated and had higher body mass index , glycosylated hemoglobin , and blood pressure . CONCLUSIONS The POP-ABC study has successfully enrolled healthy African-American and Caucasian adults with parental type 2 diabetes mellitus . The study will generate novel data on incidence rates and predictors of prediabetes , and clarify the role of race/ethnicity on early dysglycemia A 4-year prospect i ve study on the natural history of IGT in South African Indians has allowed for the evaluation of the WHO and NDDG criteria for IGT , using the five groups for non-diabetic glucose tolerance recently recommended and relating these to the risk of diabetes development . Using WHO criteria , 128 subjects were classed IGT in a baseline survey ( Year 0 ) . The five recommended categories were applied to the OGTTs done between Year 1 and Year 4 of the study , when mid-test plasma ( MPG ) sample s were also obtained . These categories included N-N ( Normal by WHO and NDDG ) ; N-ND1 ( Normal by WHO , non-diagnostic level 1 by NDDG ) ; N-ND2 ( Normal by WHO , non-diagnostic level 2 by NDDG ) ; I-ND3 ( IGT by WHO , non-diagnostic level 3 by NDDG ) and I-I ( IGT by WHO and NDDG ) . The risk of diabetes development and the significance of the non-diagnostic category were evaluated by comparing the glucose tolerance status at Year 4 with the status at Year 1 . In the cross-sectional evaluation at Year 1 , of the 87 non-diabetic OGTTs analysed , 31 % ( n = 27 ) were classified I-I , 34.5 % ( n = 30 ) were classed N-N and 34.5 % ( n = 30 ) were classified non-diagnostic [ I-ND3 ( 23.1 % ) ; N-ND2 ( 8 % ) ; N-ND1 ( 3.4 % ) ] . In the prospect i ve analysis , of the 72 subjects who completed the study , 16 subjects developed NIDDM by Year 4 ; of these 13 subjects were classed I-I and 3 subjects I-ND3 at Year 1 . ( ABSTRACT TRUNCATED AT 250 WORDS AIM To identify dietary patterns among apparently healthy individuals and to determine their long-term effect on diabetes incidence . METHODS During 2001 - 2002 , a r and om sample of 3,042 men and women ( 18 - 89 years old ) , living in greater Athens , was r and omly selected to participate in the study . During 2011 - 2012 , the 10-year follow-up was performed in 2,583 participants ( 15 % drop-out rate ) . After excluding participants with diabetes at baseline and those for whom no information on diabetes status was available at follow-up , the working sample consisted of 1,485 participants . Dietary habits were assessed by means of a vali date d semi-quantitative , food frequency question naire . Factor analysis was performed to extract dietary patterns from 18 food groups . RESULTS Diabetes diagnosis at follow-up was made in 191 participants , yielding an incidence rate of 12.9 % . Six factors ( i.e. dietary patterns ) were identified that explained 54 % of the variation in consumption . After adjusting for major confounders , and stratification by age-group , logistic regression revealed that the most healthful pattern consisted of the consumption of fruits , vegetables , legumes , bread , rusk , and pasta which reduced the 10-year diabetes risk by 40 % , among participants aged 45 - 55 years . The association reached marginal statistical significance ( 95 % CI : 0.34 , 1.07 ) , while no significant association was observed for the other age-groups . When the analysis was additionally adjusted for carbohydrate percentage , statistical significance was lost completely , suggesting a possibly mediating effect of this macronutrient . CONCLUSIONS The results confirm the potentially protective effect of a plant-based dietary pattern in the primary prevention of diabetes , in particular among middle-aged people . Carbohydrate content may be a specific factor in this relationship ; other micronutrients found in plant-based food groups may also play a role Background High levels of serum gamma-glutamyltransferase ( GGT ) are associated with increased risk of prediabetes and type 2 diabetes in observational studies . It is unclear whether this relationship is causal , arises from residual confounding or is a consequence of reverse causation . Methods We used data from a prospect i ve population -based cohort study , compromising 8611 individuals without diabetes at baseline . Cox proportional hazard models were used to study the association between serum GGT levels and incident prediabetes and diabetes . A Mendelian r and omization ( MR ) study was performed using a genetic risk score consisting of 26 GGT-related variants , based on a genome-wide association study ( GWAS ) on liver enzymes . Association with diabetes and glycaemic traits were investigated within the Rotterdam Study and large-scale GWAS . Results During follow-up , 1125 cases of prediabetes ( mean follow-up 5.7 years ) and 811 cases of type 2 diabetes ( 6.9 years ) were ascertained . The predicted hazard ratios per st and ard deviation ( SD ) change in GGT levels in the multivariable model were 1.10 for prediabetes [ 95 % confidence interval ( CI ) : 1.02 - 1.19 ] and 1.19 for type 2 diabetes ( 95 % CI : 1.10 - 1.30 ) . The genetic risk score associated with increased GGT levels ( beta per SD log GGT = 0.41 , 95 % CI : 0.35 - 0.47 ) , explaining 3.5 % of the observed variation in GGT . MR analysis did not provide evidence for a causal role of GGT , with a causal relative risk for prediabetes and type 2 diabetes per SD of log GGT of 0.97 ( 95 % CI : 0.91 - 1.04 ) and 0.96 ( 95 % CI : 0.89 - 1.04 ) , respectively . Multiple instrumental analysis using genetic associations with type 2 diabetes and glycaemic traits from previous GWA studies detected no causal effect of GGT . Conclusions MR analyses did not support a causal role of GGT on the risk of prediabetes or diabetes . The association of GGT with diabetes in observational studies is likely to be driven by reverse causation or confounding bias . As such , therapeutics targeted at lowering GGT levels are unlikely to be effective in preventing diabetes AIMS We compared the utility of glycated hemoglobin ( HbA1c ) and oral glucose tolerance ( oGTT ) in non-diabetic patients for identifying incident diabetes ; all-cause mortality ; cardiovascular disease ( CVD ) mortality ; CVD , coronary heart disease ( CHD ) , and ischemic stroke events ; and diabetes microvascular complications . METHODS Data from a New Zeal and community setting were prospect ively linked to hospitalization , mortality , pharmaceutical and laboratory test results data . After applying exclusion criteria ( prior laboratory diagnosis or history of drug treatment for diabetes or hospitalization for diabetes or CVD event ) , there were 31,148 adults who had an HbA1c and 2-h 75 g oGTT . HbA1c was measured by ion-exchange high-performance liquid chromatography , and glucose using a commercial enzymatic method . We compared glycemic measures and outcomes using multivariable Cox proportional hazards regression . RESULTS The median follow-up time was 4years ( range 0 to 13 ) . The mean age was 57·6years and 53·0 % were male . After adjusting for other glycemic measures ( fasting glucose , 2-h glucose and /or HbA1c where relevant ) in addition to age , sex , ethnicity and smoking habit , the hazard ratios for incident diabetes and diabetes complications of retinopathy and nephropathy were highest for 2-h glucose levels , followed by HbA1c and lastly by fasting glucose . However , all-cause mortality and CHD were significantly associated with HbA1c concentrations only , and ischemic stroke and CVD events with 2-h glucose only . Circulatory complications showed a stronger association with HbA1c . CONCLUSION Apart from neuropathy , HbA1c showed stronger associations with outcomes compared to fasting glucose and provides a convenient alternative to an oGTT Background There is a lack of consensus across international organizations regarding definitions of prediabetes . Associations with complications can inform the comparative value of different prediabetes definitions . Methods We conducted a prospect i ve cohort study of 10,844 Atherosclerosis Risk in Communities ( ARIC ) study participants without diagnosed diabetes who attended visit 2 ( 1990–92 ) and 7,194 who attended visit 4 ( 1996–98 ) . Fasting glucose and HbA1c were measured at visit 2 and fasting glucose and 2-hour glucose were measured at visit 4 . We compared prediabetes definitions based on fasting glucose ( American Diabetes Association [ ADA ] 5.6–6.9 mmol/L and World Health Organization [ WHO ] 6.1–6.9 mmol/L ) , HbA1c ( ADA 39–46 mmol/mol and International Expert Committee [ IEC ] 42–46 mmol/mol ) , and 2-hour glucose ( ADA/WHO 7.8–11.0 mmol/L ) . Findings ADA fasting glucose-defined prediabetes ( prevalence 37.9 % ) was the most sensitive for major clinical outcomes , while ADA and IEC HbA1c and WHO fasting glucose-based definitions ( prevalence 18.7 % , 9.0 % , 11.2 % , respectively ) were more specific . After demographic adjustment , HbA1c-based definitions of prediabetes had higher hazard ratios and demonstrated better risk discrimination for chronic kidney disease , cardiovascular disease , peripheral arterial disease , and all-cause mortality compared to fasting glucose ( modestly larger C-statistics , all p<0.05 ) . For example , the C-statistic for incident chronic kidney disease was 0.636 for ADA fasting glucose categories and 0.640 for ADA HbA1c clinical categories ( difference −0.005 , 95%CI −0.008 , −0.001 ) . Additionally , ADA HbA1c-defined prediabetes also demonstrated significant overall improvement in the net reclassification index for cardiovascular outcomes and death compared to glucose-based definitions . Comparing ADA and WHO fasting glucose and ADA/WHO 2-hour did not reveal statistically significant differences in risk discrimination for chronic kidney disease , cardiovascular , or mortality outcomes . Interpretation Our results suggest that HbA1c-defined prediabetes definitions were more specific and provided modest improvements in risk discrimination for clinical complications . ADA fasting glucose was a more sensitive definition overall OBJECTIVE This study examined associations between BMI and mortality in individuals with normoglycemia , impaired fasting glucose ( IFG ) , newly diagnosed diabetes , and prevalent diabetes and identified BMI ranges associated with the lowest mortality in each group . RESEARCH DESIGN AND METHODS A total of 12,815,006 adults were prospect ively monitored until 2013 . Diabetes status was defined as follows : normoglycemia ( fasting glucose < 100 mg/dL ) , IFG ( 100–125 mg/dL ) , newly diagnosed diabetes ( ≥126 mg/dL ) , and prevalent diabetes ( self-reported ) . BMI ( kg/m2 ) was measured . Cox proportional hazards model hazard ratios were calculated after adjusting for confounders . RESULTS During a mean follow-up period of 10.5 years , 454,546 men and 239,877 women died . U-shaped associations were observed regardless of diabetes status , sex , age , and smoking history . Optimal BMI ( kg/m2 ) for the lowest mortality by group was 23.5–27.9 ( normoglycemia ) , 25–27.9 ( IFG ) , 25–29.4 ( newly diagnosed diabetes ) , and 26.5–29.4 ( prevalent diabetes ) . Higher optimal BMI by worsening diabetes status was more prominent in younger ages , especially in women . The relationship between worsening diabetes status and higher mortality was stronger with lower BMI , especially at younger ages . Given the same BMI , people with prevalent diabetes had higher mortality compared with those with newly diagnosed diabetes , and this was more striking in women than men . CONCLUSIONS U-curve relationships existed regardless of diabetes status . Optimal BMI for lowest mortality became gradually higher with worsening diabetes for each sex and each age-group OBJECTIVE Many individuals with prediabetes have evidence of sub clinical myocardial damage and are at an increased risk of cardiovascular disease ( CVD ) . If sub clinical myocardial damage is independently associated with incident diabetes , this may contribute to the underst and ing of the association between diabetes and CVD . This study was conducted to determine whether high-sensitivity cardiac troponin T ( hs-cTnT ) is associated with incident diabetes . RESEARCH DESIGN AND METHODS Using Kaplan-Meier curves and Cox models , we prospect ively analyzed 8,153 participants without known diabetes or CVD . We used the Harrell C statistic to investigate whether hs-cTnT added incremental prognostic information for diabetes prediction . RESULTS During a median of 13 years of follow-up , there were 1,830 incident cases of diagnosed diabetes . After adjustment for demographics and traditional risk factors , participants with a baseline hs-cTnT of 9–13 ng/L or ≥14 ng/L had a significantly increased risk for diabetes compared to those with an hs-cTnT of ≤5 ng/L , with hazard ratios of 1.14 ( 95 % CI 0.99–1.33 ) and 1.25 ( 95 % CI 1.03–1.53 ) , respectively ( P = 0.018 for trend ) . Linear spline modeling that included adjustment for baseline fasting glucose suggested an increased risk of incident diabetes for participants with hs-cTnT levels > 8 ng/L. Furthermore , the addition of hs-cTnT to fully adjusted models that included glucose significantly improved the prediction of incident diabetes from 0.7636 to 0.7644 ( P = 0.023 ) . CONCLUSIONS Participants with elevated hs-cTnT levels at baseline had an increased risk of incident diabetes , suggesting that the measurement of hs-cTnT may incorporate an underlying pathophysiologic overlap between diabetes and CVD not captured by other traditional risk factors . Measurement of hs-cTnT may be useful to identify individuals at an increased risk for incident diabetes and CVD in order to provide early and more intensive risk factor modification |
2,193 | 30,679,296 | Conclusions Complex , interlinking , multilevel barriers to accessing mental health services for women with perinatal mental illness exist . | Objective Lack of access to mental health services during the perinatal period is a significant public health concern in the UK .
Barriers to accessing services may occur at multiple points in the care pathway .
However , no previous review s have investigated multilevel system barriers or how they might interact to prevent women from accessing services .
This review examines women , their family members ’ and healthcare providers ’ perspectives of barriers to accessing mental health services for women with perinatal mental illness in the UK . | Background Postnatal depression affects 10–15 % of all mothers in Western societies and remains a major public health concern for women from diverse cultures . British Pakistani and Indian women have a higher prevalence of depression in comparison to their white counterparts . Research has shown that culturally adapted interventions using Cognitive Behavioural Therapy ( CBT ) may be acceptable and may help to address the needs of this population . The aim of this study was to assess the acceptability and overall experience of the Positive Health Programme by British South Asian mothers . Methods This was a nested qualitative study , part of an exploratory r and omized controlled trial ( RCT ) conducted to test the feasibility and acceptability of a culturally-adapted intervention ( Positive Health Programme or PHP ) for postnatal depression in British South Asian women . In-depth interviews ( N = 17 ) were conducted to determine the views of the participants on the feasibility and acceptability of the intervention . Results The participants found the intervention acceptable and experienced an overall positive change in their attitudes , behaviour , and increased self-confidence . Conclusions The findings suggest that the culturally adapted Positive Health Programme is acceptable to British South Asian women . These results support that culturally sensitive interventions may lead to better health outcomes and overall satisfaction . Trial registration Protocol registered on Clinical trials.gov Background In the UK , 8–15 % of women suffer from postnatal depression with long term consequences for maternal mood and child development . Current guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression . Previous literature suggests that women are reluctant to disclose symptoms of postnatal depression . This study aim ed to explore general practitioners ' ( GPs ) , health visitors ' and women 's views on the disclosure of symptoms which may indicate postnatal depression in primary care . Methods In-depth interviews with GPs , health visitors and women who were participating in a r and omised controlled trial of anti-depressants versus health visitor delivered non-directive counselling for the treatment of postnatal depression . Interviews were audio-taped and fully transcribed . Thematic analysis with an iterative approach was used , allowing the views of practitioners and patients to be explored and then compared . Results Nineteen GPs , 14 health visitors and 28 women were interviewed . A number of common themes were identified across all three data sets : underst and ing and negotiating the diagnosis of postnatal depression , hindering and facilitating disclosure , and the system of care . Both women and health professionals described postnatal depression in psychosocial terms : an adjustment reaction to change in life circumstances and the reality of motherhood not meeting personal expectations . Women described making a conscious decision about whether or not to disclose their feelings to their GP or health visitor . Health professionals described strategies used to hinder disclosure and described a reluctance to make a diagnosis of postnatal depression , as they had few personal re sources to manage women with postnatal depression themselves , and no services to which to refer women for further treatment . Conclusion To improve disclosure of symptoms in primary care , there should be a move away from question ing why health professionals do not make the diagnosis of depression and in response suggesting that education and training will improve skills and thus improve detection of depression . Improving the detection and management of postnatal depression in primary care requires recognition of the context in which women consult , and system changes that ensure health professionals work in an environment that can facilitate disclosure and that the necessary re sources for management are available . Trail Registration IS RCT N BACKGROUND In the UK , 8 - 15 % of women suffer from postnatal depression , with long-term consequences for maternal mood and child development . Previous literature suggests that health visitors struggle with their conflicting roles with respect to mother and infant . Current policy is redirecting the emphasis and organisation of health visitor work , but guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression . AIM To explore the views of GPs and health visitors on the diagnosis and management of postnatal depression . DESIGN OF STUDY A qualitative study nested within a multicentre r and omised controlled trial . SETTING Nine primary care trusts in Bristol , Manchester , and London . METHOD In-depth interviews with GPs and health visitors from primary care trusts participating in a r and omised controlled trial of antidepressants versus health visitor-delivered non-directive counselling . Interviews were audiotaped and fully transcribed . Thematic analysis with an iterative approach was used to develop conceptual categories from the transcripts . RESULTS Nineteen GPs and 14 health visitors were interviewed . GPs and health visitors described their work in making and negotiating the diagnosis of postnatal depression , the value of a long-term relationship with the woman , and how labelling affects management of women with postnatal depression . Responders described how they viewed others ' roles in the management of postnatal depression , and how national policy and local organisational changes had an impact on patient care , so that no one health professional was assuming overall responsibility for the care of women with postnatal depression . CONCLUSION Ongoing organisational changes within primary care , such as the implementation of corporate working by health visitors , affect care provided to women after birth , which in turn has an impact on the diagnosis and management of postnatal depression BACKGROUND Postnatal depression is a public health problem requiring intervention . To provide effective care , information is needed on the experiences of those with high levels of depressive symptoms who are offered and accept , or decline , psychological intervention postnatally . AIM To provide the first integrated in-depth exploration of postnatal women 's experiences of the identification and management of symptoms of depression and the offer and acceptance of postnatal care by health visitors taking part in the PoNDER trial . SETTING General practice : primary care within the former Trent regional health authority , Engl and . METHOD Thirty women with 6-week Edinburgh Postnatal Depression Scale ( EPDS ) scores ≥ 18 and probable depression completed semi-structured interviews . All women had taken part in the Post-Natal Depression Economic Evaluation and R and omised controlled ( PoNDER ) trial where intervention group health visitors received training in identification of depressive symptoms and provided psychologically informed sessions based on cognitive-behavioural therapy or person-centred counselling principles . RESULTS When accepted , psychological sessions were experienced as positive , effective , and ' ideal care ' . Women approved of using the EPDS but did not underst and the health visitor 's role in supporting women . Seeking help and accepting sessions depended on women 's perspectives of their health visitor as an individual . CONCLUSION Women 's experience of their health visitors providing psychological sessions to help with postnatal depressive symptoms is highly positive . Women will better accept support from health visitors if they recognise their role in postnatal depression and find them easy to relate to on personal matters . There is a case for specific enhancement of interpersonal skills in health visiting , or alternatively offering a choice of health visitors to women |
2,194 | 31,142,524 | Overall , validity of each triage system to identify high and low-urgency patients was moderate to good , but performance was highly variable .
In a subgroup analysis , no clear association was found between ED patient volume or casemix severity of illness and triage systems ' performance .
Established triage systems show a reasonable validity for the triage of patients at the ED , but performance varies considerably . | OBJECTIVE To assess and compare the performance of triage systems for identifying high and low-urgency patients in the emergency department ( ED ) . | The aim of this study was to compare the performance of the Paediatric Canadian Triage and Acuity Scale ( Paed CTAS ) to a previous triage tool with respect to the percentage of admissions , the diagnostic and therapeutic interventions , and the mean pediatric risk of admission ( PRISA ) score in a pediatric tertiary center emergency department . Data were prospect ively collected for 4 months before the Paed CTAS introduction ( PRE group ) and for 4 months after its implementation ( Paed CTAS group ) . Both groups were similar in chief complaints , distribution of triage levels , and mean PRISA score . In the Paed CTAS group , more patients were triaged in the higher acuity levels ( 53 % vs 36 % , P < .05 ) , but the percentage of admission for these patients was comparatively lower ( 13 % vs 27 % , P<.05 ) . The ability to predict admission was greater for the PRE tool as compared to the Paed CTAS tool ( AUC : 0.82 vs 0.69 , P=.001 ) . The ability to predict requirements for interventions such as blood culture and intravenous fluid bolus was similar for both triage tools OBJECTIVES The objective was to compare the validity of an existing informally structured triage system with the Emergency Severity Index ( ESI ) and the Manchester Triage System ( MTS ) . METHODS A total of 900 patients were prospect ively triaged by six trained triage nurses using the three systems . Triage ratings of 421 ( 48 % ) patients treated only by emergency department ( ED ) physicians were compared with a reference st and ard determined by an expert panel . The percentage of undertriage , the sensitivity , and the specificity for each urgency level were calculated . The relationship between urgency level , re source use , hospitalization , and length of stay ( LOS ) in the 900 triaged patients was determined . RESULTS The percentage of undertriage using the ESI ( 86 of 421 ; 20 % ) was significantly higher than in the MTS ( 48 of 421 ; 11 % ) . When combining urgency levels 4 and 5 , the percentage of undertriage was 8 % for the informally structured system ( ISS ) , 14 % for the ESI , and 11 % for the MTS . In all three systems , sensitivity for all urgency levels was low , but specificity for levels 1 and 2 was high ( > 92 % ) . Sensitivity and specificity were significantly different between ESI and MTS only in urgency level 4 . In all 900 patients triaged , urgency levels across all systems were associated with significantly increased re source use , hospitalization rate , and LOS . CONCLUSIONS All three triage systems appear to be equally valid . Although the ESI showed the highest percentage of undertriage and the ISS the lowest , it seems preferable to use a verifiable , formally structured triage system BACKGROUND / PURPOSE Since the implementation of National Health Insurance in Taiwan , Emergency Department ( ED ) volume has progressively increased , and the current triage system is insufficient and needs modification . This study compared the prioritization and re source utilization differences between the four-level Taiwan Triage System ( TTS ) and the st and ardized five-level Canadian Triage and Acuity Scale ( CTAS ) among ED patients . METHODS This was a prospect i ve observational study . All adult ED patients who presented to three different medical centers during the study period were included . Patients were independently triaged by the duty triage nurse using TTS , and a single trained research nurse using CTAS with a computer support software system . Hospitalization , length of stay ( LOS ) , and medical re source consumption were analyzed by comparing TTS and CTAS by acuity levels . RESULTS There was significant disparity in patient prioritization between TTS and CTAS among the 1851 enrolled patients . With TTS , 7.8 % , 46.1 % , 45.9 % and 0.2 % were assigned to levels 1 , 2 , 3 , and 4 , respectively . With CTAS , 3.5 % , 24.4 % , 44.3 % , 22.4 % and 5.5 % were assigned to levels 1 , 2 , 3 , 4 , and 5 , respectively . The hospitalization rate , LOS , and medical re source consumption differed significantly between the two triage systems and correlated better with CTAS . CONCLUSION CTAS provided better discrimination for ED patient triage , and also showed greater validity when predicting hospitalization , LOS , and medical re source consumption . An accurate five-level triage scale appeared superior in predicting patient acuity and re source utilization INTRODUCTION The study objectives were to compare reliability and validity of a 3-level ( 3L ) triage system with a new 5-level ( 5L ) triage system and determine the effect of nursing experience on triage reliability . METHODS The study was conducted in a southeastern tertiary emergency department . With a stratified r and om sample , reliability of 3L triage ratings was measured with weighted kappa ( time 1 ) . The 5L system was then implemented , and weighted kappa was remeasured ( time 2 ) . Validity was assessed by comparing case mix , sensitivity , and specificity at times 1 and 2 , and comparing 5L ratings with physician billing ( Evaluation and Management ) codes and nursing re source intensity at time 2 . RESULTS Time 1 case mix ( 15,324 patients ) was : level 1 , 6 % ; level 2 , 36 % ; level 3 , 59 % , and time 2 ( 16,024 patients ) was : level 1 , 1 % ; level 2 , 8 % ; level 3 , 38 % ; level 4 , 41 % ; level 5 , 13 % . Three hundred-five triage ratings were evaluated from time 1 , and 303 were evaluated from time 2 . Weighted kappa was 0.53 for time 1 and 0.68 for time 2 . Spearman correlations were : 5L and nursing re source intensity , 0.55 ( P < .0001 ) ; and 5L and Em , 0.57 ( P < .0001 ) . Sensitivity was 58 % for the 3L and 68 % for the 5L . Specificity was 83 % for the 3L and 91 % for the 5L . Under-triage rates were 28 % for the 3L and 12 % for the 5L , and less-experienced nurses were more likely to under-triage using the 3L system . DISCUSSION The 5L triage system is safer and provides greater discrimination , better reliability , and improved sensitivity and specificity than the 3L triage system Objective An ideal emergency department ( ED ) triage system accurately prioritises patients on the basis of the urgency of interventions required to avoid under- or over-triage . The objective of this study was to develop and vali date a five-level Taiwan triage and acuity scale ( TTAS ) with an electronic decision support tool . Methods This prospect i ve , multicentre , observational study included 10533 patients triaged at 11 academic medical centres , 18 regional and four district hospitals . Adult patients presenting to the ED were independently triaged by the duty triage nurse in the usual way and trained research nurses using TTAS with a computerised decision support system . Weighted κ statistics were used to assess the reproducibility . Hospitalisation , length of stay , and medical re source consumption were analysed by TTAS acuity levels . Results Most cases were stratified into levels 2 to 3 by the existing four-level triage system , whereas the TTAS stratified most patients to levels 3 ( 41.4 % ) and 4 ( 25.0 % ) , and only a small number to level 1 ( 3.9 % ) ( resuscitation ; most urgent ) . Weighted κ for TTAS assignment was 0.87 ( 95 % CI 0.85 to 0.89 ) . The decrease in mean medical re source consumption and hospitalisation rate was statistically significant with each decrease in the TTAS triage acuity level . The length of stay also decreased significantly as the TTAS level acuity fell from levels 2 to 5 . Conclusions The TTAS was found to be a reliable triage system that accurately prioritises the treatment needed to avoid overtriage , more efficiently deploying the appropriate re sources to ED patients INTRODUCTION Each of the two most commonly used five-level triage tools in North America , the Emergency Severity Index and the Canadian Triage and Acuity Scale have been used as a measure of emergency department re source utilization in addition to acuity . In both cases , it is believed that patients triaged as having a higher level of acuity require a greater number of emergency department re sources . We compared the ability of each tool to predict the emergency department re sources for each emergency department visit and associated hospital admission and in-hospital mortality rates . METHODS This is an observational , cohort study of a population -based r and om sample of patients triaged at two emergency departments over a 4-month period . Correlational analyses were performed to examine the relationship between the triage assessment and : ( i ) re source utilization , ( ii ) hospital admission , and ( iii ) in-hospital mortality . RESULTS From 486 patients , analyses revealed the greatest correlation was between Emergency Severity Index and diagnostic re sources [ -0.54 ( 95 % confidence intervals : -0.58 , -0.50 ) ] and the poorest correlation was between Canadian Triage and Acuity Scale and mortality [ -0.16 ( 95 % confidence intervals : -0.20 , -0.12 ) ] . No statistically significant differences ( P<0.005 ) were observed between each tool 's ability to predict any of the outcomes measured . CONCLUSION No statistically significant difference was observed in the ability of Emergency Severity Index v. 3 and Canadian Triage and Acuity Scale to predict emergency department re source utilization or immediate patient outcomes . This ability is , at best , only moderate indicating that other , more accurate tools than measures of triage acuity are required for this purpose BACKGROUND Triage system in children seems to be more challenging compared to adults because of their different response to physiological and psychosocial stressors . This study aim ed to determine the best triage system in the pediatric emergency department . METHODS This was a prospect i ve observational study . This study was divided into two phases . The first phase determined the inter-rater reliability of five triage systems : Manchester Triage System ( MTS ) , Emergency Severity Index ( ESI ) version 4 , Pediatric Canadian Triage and Acuity Scale ( CTAS ) , Australasian Triage Scale ( ATS ) , and Ramathibodi Triage System ( RTS ) by triage nurses and pediatric residents . In the second phase , to analyze the validity of each triage system , patients were categorized as two groups , i.e. , high acuity patients ( triage level 1 , 2 ) and low acuity patients ( triage level 3 , 4 , and 5 ) . Then we compared the triage acuity with actual admission . RESULTS In phase I , RTS illustrated almost perfect inter-rater reliability with kappa of 1.0 ( P<0.01 ) . ESI and CTAS illustrated good inter-rater reliability with kappa of 0.8 - 0.9 ( P<0.01 ) . Meanwhile , ATS and MTS illustrated moderate to good inter-rater reliability with kappa of 0.5 - 0.7 ( P<0.01 ) . In phase II , we included 1 041 participants with average age of 4.7±4.2 years , of which 55 % were male and 45 % were female . In addition 32 % of the participants had underlying diseases , and 123 ( 11.8 % ) patients were admitted . We found that ESI illustrated the most appropriate predicting ability for admission with sensitivity of 52 % , specificity of 81 % , and AUC 0.78 ( 95%CI 0.74 - 0.81 ) . CONCLUSION RTS illustrated almost perfect inter-rater reliability . Meanwhile , ESI and CTAS illustrated good inter-rater reliability . Finally , ESI illustrated the appropriate validity for triage system Objective To measure and compare the reliability and predictive validity of a four-level triage system ( I-4L ) and the new four-level model triage emergency method ( TEM ) . Methods This observational study was conducted in an urban hospital . Ten nurses were r and omly selected to assign a triage level to 189 paper scenarios , using either the I-4L model ( 5 nurses ) or the TEM model ( 5 nurses ) . We used weighted κ statistics to measure the interrater and intrarater reliability of each triage tool and assessed the validity of each models based on the accuracy in predicting admission . Results Interrater reliability was κ=0.73 [ 95 % CI ( confidence interval ) : 0.59–0.87 ] and κ=0.79 ( 95 % CI : 0.65–0.93 ) with I-4L and TEM , respectively . Intrarater reliability was κ=0.82 ( 95 % CI : 0.67–0.96 ) and κ=0.78 ( 95 % CI : 0.62–0.93 ) , respectively . The accuracy of triage rating for admission prediction was similarly good with I-4L and TEM , namely , 79 % ( 95 % CI : 74–85 ) and 77 % ( 95 % CI : 74–85 ) . The proportion of patients admitted per triage level was similar with the two models . Conclusion The interrater and intrarater reliability for rating triage acuity and for accuracy in patient admission prediction was good with both models . Performance with the new model was similar to that of I-4L despite the nurses ' short experience . The new TEM model has the advantage of predicting utilization of emergency department re sources Objective : To evaluate the validity , reliability , sensitivity , and specificity of the Emergency Severity Index ( ESI ) and Australasian Triage System ( ATS ) for children visiting admitted to the emergency department ( ED ) . Methods : This was a prospect i ve study occurred in the Mofid children 's Hospital in Iran from August 2017 to November 2018 and children had aged ≤14 years and presented at the ED with a medical symptom were considered eligible for participation . This study was divided into two phases : in the first phase , we determined the inter-rater reliability of ESI version 4 and ATS by triage nurses and pediatric residents . In the second phase , to analyze the validity , sensitivity , and specificity of each triage system . Reliability and agreement rates were measured using kappa statistics . Results : ESI showed inter-rater reliability with kappa of 0.65–0.92 ( P<0.001 ) and ATS showed inter-rater reliability with kappa of 0.51–0.87 ESI had sensitivity ranged from 81 % to 95 % and specificity ranged from 73 % to 86 % . In addition , sensitivity ranged of the ATS were 80 % to 95 % and specificity ranged from 74 % to 87 % . Under triage and over triage occurred in 12 % and 15 % of patients respectively in ESI and 13 % and 15 % of patients respectively in ATS . Conclusion : The ESI and ATS both valid to triage children in the ED section of Mofid children 's Hospital paediatric . Reliability of the ESI is good , moderate to good for the ATS |
2,195 | 31,621,155 | There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials . | BACKGROUND There is substantial variation in how menopausal vasomotor symptoms are reported and measured among intervention studies .
This has prevented meaningful comparisons between treatments and limited data synthesis .
OBJECTIVES To systematic ally review outcome reporting and measures used to assess menopausal vasomotor symptoms from r and omised controlled trials of treatments . | Objective This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms ( VMS ) frequency and bother . Methods This study was a three-by-two factorial , r and omized controlled trial . Eligible women were r and omized to yoga ( n = 107 ) , exercise ( n = 106 ) , or usual activity ( n = 142 ) , and were simultaneously r and omized to a double-blind comparison of & ohgr;-3 fatty acid ( n = 177 ) or placebo ( n = 178 ) capsules . Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice . Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline , 6 weeks , and 12 weeks . Secondary outcomes included insomnia symptoms ( Insomnia Severity Index ) at baseline and 12 weeks . Results Among 249 r and omized women , 237 ( 95 % ) completed 12-week assessment s. The mean baseline VMS frequency was 7.4 per day ( 95 % CI , 6.6 to 8.1 ) in the yoga group and 8.0 per day ( 95 % CI , 7.3 to 8.7 ) in the usual activity group . Intent-to-treat analyses included all participants with response data ( n = 237 ) . There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks ( mean difference [ yoga − usual activity ] from baseline at 6 wk , −0.3 [ 95 % CI , −1.1 to 0.5 ] ; mean difference [ yoga − usual activity ] from baseline at 12 wk , −0.3 [ 95 % CI , −1.2 to 0.6 ] ; P = 0.119 across both time points ) . Results were similar for VMS bother . At week 12 , yoga was associated with an improvement in insomnia symptoms ( mean difference [ yoga − usual activity ] in the change in Insomnia Severity Index , 1.3 [ 95 % CI , −2.5 to −0.1 ] ; P = 0.007 ) . Conclusions Among healthy women , 12 weeks of yoga class plus home practice , compared with usual activity , do not improve VMS frequency or bother but reduce insomnia symptoms Objectives This study aim ed to investigate the effect of Educational program on quality of life ( QOL ) in menopausal women in 2016 in Hamadan , Iran . Methods In this clinical trial study , 100 postmenopausal women were r and omly selected and allocated to case and control group ( 50 per group ) . Data collection tool included question naires of demographic information and Menopause QOL , which were completed by the sample s before the intervention . In the case group , education program was run during 5 sessions for 45 to 60 minutes . Immediately and Three months after intervention , information were collected using question naire in both groups and they were analyzed using SPSS 16 software . Results The menopause women in both intervention and control groups had similar demographics . There was not a significant difference in the QOL mean scores in before of the intervention between the two groups of intervention and control in all dimension of QOL . There was a significantly difference in the mean of QOL scores between the two groups in immediately after the intervention and 3 months after the intervention in dimension of vasomotor , psychosocial , sexual and physical ( P < 0.001 ) . Conclusions This study recommend that a unit in health and treatment centers be established for training menopausal women about health care by holding didactic classes Menopausal Hormone Therapy ( MHT ) use in Australia fell by 55 % from 2001 to 2005 , following the release of large-scale findings on its risks and benefits . Comprehensive national data , including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004–5 National Health Survey , when 11 % of women aged 45 + years were estimated to be current MHT users . No national data are available on prevalence of use of “ bioidentical ” hormone therapy ( BHT ) . The objective of this study was to determine recent prevalence of MHT and BHT use . A cross-sectional , national , age-stratified , population survey was conducted in 2013 . Eligible women , aged 50–69 years , resident in Australia were r and omly sample d in 5-year age groups from the Medicare enrolment data base ( Australia ’s universal health scheme ) . The response rate was 22 % based on return of completed question naires , and analyses were restricted to 4,389 women within the specified age range . The estimated population -weighted prevalence of current use of MHT was 13 % ( 95%CI 12–14 ) , which was broadly similar to the previously reported national figures in 2004–5 , suggesting that the use of MHT in Australia has largely stabilised over the past decade . A total of 39 % and 20 % of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT , respectively , whereas 77 % of hysterectomised current-users used oestrogen-only MHT . Almost three-quarters of current-users [ population -weighted prevalence 9 % ( 95%CI 8–10 ) ] had used MHT for ≥5 years . In regard to BHT , estimated population -weighted prevalence of ever use was 6 % ( 95%CI 6–7 ) and 2 % ( 95%CI 2–3 ) for current use . The population -weighted prevalence of MHT and BHT combined , in current users in their fifties and sixties was 15 % ( 95%CI 14–16 ) . These data provide a recent national “ snapshot ” of Australian women ’s use of both conventional MHT and of BHT Clinical trials , systematic review s and guidelines compare beneficial and non-beneficial outcomes following interventions . Often , however , various studies on a particular topic do not address the same outcomes , making it difficult to draw clinical ly useful conclusions when a group of studies is looked at as a whole.1 This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention , which found that among 103 r and omised trials , no fewer than 72 different outcomes were reported.2 There is a growing recognition among clinical research ers that this variability undermines consistent synthesis of the evidence , and that what is needed is an agreed st and ardised collection of outcomes – a “ core outcomes set ” – for all trials in a specific clinical area.1 Recognising that the current inconsistency is a serious hindrance to progress in our specialty , the editors of over 50 journals related to women 's health have come together to support The CROWN ( CoRe Outcomes in WomeN 's health ) Initiative ( Box 1 ) . ! [Graphic][1 ] Box 1 # # # Aims of The CROWN Initiative ( http://www.crown-initiative.org ) 1 . Form a consortium among all gynaecology-obstetrics and related journals to promote core outcome sets in all areas of our specialty . … [ 1 ] : Background Natural estrogen decline leads to vasomotor symptoms ( VMS ) . Hormone therapy alleviates symptoms but increases cancer risk . Effective treatments against VMS with minimal cancer risks are needed . We investigate the effects of a highly bioavailable aglycone rich Red Clover isoflavone treatment to alleviate existing menopausal VMS , assessed for the first time by 24hour ambulatory skin conductance ( SC ) Methods and results We conducted a parallel , double blind , r and omised control trial of 62 peri-menopausal women aged 40–65 , reporting ≥ 5 hot flushes/day and follicle stimulating hormone ≥35 IU/L. Participants received either twice daily treatment with bioavailable RC extract ( RCE ) , providing 34 mg/d isoflavones and probiotics , or masked placebo formulation for 12 weeks . The primary outcome was change in daily hot flush frequency ( HFF ) from baseline to 12 weeks using 24hr SC . Secondary outcomes were change in SC determined hot flush intensity ( HFI ) , self-reported HFF ( rHFF ) and hot flush severity ( rHFS ) , blood pressure and plasma lipids . A significant decrease in 24hr HFF ( P < 0.01 ) and HFI ( P<0.05 ) was found when comparing change from baseline to 12 months of the RCE ( -4.3 HF/24hr , CI -6.8 to -2.3 ; -12956 μS s-1 , CI -20175 to -5737 ) with placebo ( 0.79 HF/24hr , CI -1.56 to 3.15 ; 515 μS s-1 , CI -5465 to 6496 ) . rHFF was also significantly reduced ( P < 0.05)in the RCE ( -2.97 HFs/d , CI -4.77 to -1.17 ) group compared to placebo ( 0.036 HFs/d , CI -2.42 to 2.49 ) . Other parameters were non-significant . RCE was well tolerated . Conclusion Results suggest that moderate doses of RCE were more effective and superior to placebo in reducing physiological and self-reported VMS . Findings support that objective physiological symptom assessment methods should be used together with self-report measures in future studies on menopausal VMS . Trial registration Clinical Trials.gov CONTEXT St and ard therapy for hot flashes has been hormone replacement with estradiol or progestational agents , but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective . OBJECTIVE To evaluate a selective serotonin reuptake inhibitor ( paroxetine controlled release [ CR ] ) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women . DESIGN AND SETTING R and omized , double-blind , placebo-controlled , parallel group study conducted across 17 US sites , including urban , suburban , and rural clinics . PATIENTS A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks . Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy . INTERVENTION After a 1-week placebo run-in phase , study participants were r and omized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR ( in a 1:1:1 ratio ) for 6 weeks . MAIN OUTCOME MEASURES Mean change from baseline to week 6 in the daily hot flash composite score ( frequency x severity ) . RESULTS Fifty-six participants were r and omly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR . The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo . By week 6 , the mean daily hot flash frequency went from 7.1 to 3.8 ( mean reduction , 3.3 ) for those in the 12.5-mg/d and from 6.4 to 3.2 ( mean reduction , 3.2 ) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 ( mean reduction , 1.8 ) for those in the placebo group . Mean placebo-adjusted reduction in hot flash composite scores were -4.7 ( 95 % confidence interval , - 8.1 to -1.3 ; P = .007 ) comparing 12.5-mg/d paroxetine CR with placebo ; and -3.6 ( 95 % confidence interval , -6.8 to -0.4 ; P = .03 ) comparing 25.0-mg/d paroxetine CR with placebo . This corresponded to median reductions of 62.2 % for those in the 12.5-mg/d and 64.6 % for those in the 25.0-mg/d paroxetine CR groups compared with 37.8 % for those in the placebo group . CONCLUSION Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms OBJECTIVE To evaluate the efficacy comparison of Pueraria mirifica ( PM ) , name in Thai is Kwao Kruea Khao , against conjugated equine estrogen ( CEE ) with/without medroxyprogesterone acetate ( MPA ) in the treatment of perimenopuasal women with climacteric symptoms . MATERIAL AND METHOD Perimenopausal women attending the Menopausal clinic of Hat Yai Regional Hospital were voluntarily recruited . The vasomotor symptoms such as hot flushes and night sweats , as well as other unpleasant symptoms , urogenital and psychological symptoms , were also assessed . Patients were voluntarily enrolled and r and omly received daily 50 mg raw material of PM , Group A , or daily 0.625 mg of conjugated equine estrogen ( CEE ) with/without 2.5 mg of medroxyprogesterone acetate ( MPA ) , Group B , depend on non-hysterectomized/hysterectomized condition . RESULTS Seventy-one patients were enrolled . Eleven of those were excluded for failing to complete the initial work-up and follow-up . Sixty cases were evaluated , 30 cases in Group A and 30 cases in Group B. After medication , the mean of modified Greene climacteric scale ( MGCS ) in Group A/Group B had decreased from 29.0/32.26 to 17.86/18.1 , 12.56/9.57 and 9.9/8.16 at 1- , 3- , and 6- month respectively . The clinical satisfaction using MGCS was not statistically significant between PM ( Group A ) and CEE with/without MPA ( Group B ) in the alleviation of climacteric symptoms ( p-value > 0.05 ) . There were no statistically significant changes of three serum markers : estradiol , follicle-stimulating hormone ( FSH ) , and luteinizing hormone ( LH ) between both groups . CONCLUSION PM , containing phytoestrogens , has estrogenic effect as similar as CEE , and can alleviate the climacteric symptoms in perimenopausal women . PM demonstrates great promise in the treatment of climacteric symptoms . However , optimal doses should be clinical ly assessed to meet appropriate individual responses The objective of this study was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of women with postmenopausal symptoms . A total of 120 healthy women with menopausal symptoms were recruited to this prospect i ve study with a follow-up period of 6 mo . They were r and omly assigned to 1 of 2 groups and were treated with fluoxetine or black cohosh . After entry into the study , patients were examined at the first , second , third , and sixth months of the treatment period . The women kept diaries in which they reported the daily number and intensity of hot flushes and night sweats . In addition , at the beginning and end of the third month , they completed question naires consisting of a modified Kupperman Index , Beck ’s Depression Scale , and a R AND -36 Quality -of-Life Question naire . Statistically significant differences were noted in the Kupperman Index and Beck ’s Depression Scale at the end of the third month in both groups compared with baseline values . In the black cohosh group , the Kupperman Index decreased significantly compared with that in the fluoxetine group by the end of the third month . On the other h and , in the fluoxetine group , Beck ’s Depression Scale decreased significantly compared with that in the black cohosh group . Monthly scores for hot flushes and night sweats decreased significantly in both groups ; however , black cohosh reduced monthly scores for hot flushes and night sweats to a greater extent than did fluoxetine . At the end of the sixth month of treatment , black cohosh reduced the hot flush score by 85 % , compared with a 62 % result for fluoxetine . By the sixth month of the study , 40 women had discontinued the study —20 ( 33 % ) in the fluoxetine group and 20 ( 33 % ) in the black cohosh group . Compared with fluoxetine , black cohosh is more effective for treating hot flushes and night sweats . On the other h and , fluoxetine is more effective in improvements shown on Beck ’s Depression Scale BACKGROUND tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints , without affecting endometrial thickness and lipid profile or blood glucose . However , the potentially similar efficacy , but better tolerability , of a low dose of this drug ( 1.25 mg ) has never been established . METHODS 162 healthy , non-obese , post-menopausal women , aged 40 - 65 years , with an intact uterus were enrolled in a national , single centre , r and omised , double blind , placebo controlled , parallel group trial . After 1 week of runin , patients were treated for 24 weeks with placebo , tibolone 1.25 mg or 2.5 mg/day . During the study laboratory tests , endometrial ultrasound scans and mammography were performed . Occurrence of menopausal signs and symptoms , including vaginal bleeding , and quality of sexual life were also checked . RESULTS in the 120 patients terminating the study without major protocol violations , climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg ( 78 % and 90 % reduction at week 24 for hot flushes , 36 % and 34 % for sweating episodes and 44 % and 51 % for vaginal dryness ) , but not by placebo . Benefits occurred earlier in the group treated with tibolone 2.5 mg . Quality of sexual life was almost invariably improved by tibolone as compared to placebo , but improvement occurred earlier in the tibolone 1.25 mg group . Severity of vaginal bleeding was not different between placebo and active treatment groups , except at week 12 when was higher . At the end of treatment vaginal bleeding occurred in 15 % of patients treated with placebo , 14 % treated with tibolone 1.25 mg and 12 % treated with tibolone 2.5 mg . Endometrial thickness and breast density were not changed by treatment , as well as FSH , 17-beta-estradiol , total cholesterol , HDL and LDL cholesterol , triglycerides and blood glucose . Adverse events were reported by 14.7 % , 26.7 % and 24.4 % of patients treated with placebo , tibolone 1.25 mg and tibolone 2.5 mg/day , respectively . CONCLUSIONS tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles , though were more effective than placebo . Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function Objective To assess the effects of tibolone on climacteric symptoms , endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer OBJECTIVE To estimate the effect of escitalopram ( 10 - 20 mg/d ) versus placebo for reducing hot flash interference in daily life and underst and correlates and predictors of reductions in hot flash interference , a key measure of quality of life . DESIGN Multisite , r and omized , double-blind , placebo-controlled clinical trial . SETTING MsFLASH clinical sites in Boston , Indianapolis , Oakl and , and Philadelphia . PATIENT(S ) A total of 205 midlife women ( 46 % African-American ) who met criteria participated . INTERVENTION(S ) After baseline , women were r and omized to one pill of escitalopram 10 mg/d ( n = 104 ) or placebo ( n = 101 ) with follow-up at 4 and 8 weeks . At week 4 , those not achieving 50 % fewer hot flashes were increased to two pills daily ( 20 mg/d or 2 placebo pills ) . MAIN OUTCOME MEASURE(S ) The Hot Flash Related Daily Interference Scale ; correlates were variables from hot flash diaries ; predictors were baseline demographics , clinical variables , depression , anxiety , sleep quality , and hot flashes . RESULT ( S ) Compared to placebo , escitalopram significantly reduced hot flash interference by 6.0 points at week 4 and 3.4 points at week 8 more than placebo . Reductions in hot flash interference correlated with changes in hot flash diary variables . However , baseline variables did not significantly predict reductions in hot flash interference . CONCLUSION ( S ) Escitalopram ( 10 - 20 mg/d ) for 8 weeks improves women 's quality of life and this benefit did not vary by demographic , clinical , mood , sleep , or hot flash variables . CLINICAL TRIAL REGISTRATION NUMBER NCT00894543 PURPOSE The purpose of our study was to evaluate the effect of cognitive behavioral therapy ( CBT ) , physical exercise ( PE ) , and of these two interventions combined ( CBT/PE ) on menopausal symptoms ( primary outcome ) , body image , sexual functioning , psychological well-being , and health-related quality of life ( secondary outcomes ) in patients with breast cancer experiencing treatment-induced menopause . PATIENTS AND METHODS Patients with breast cancer reporting treatment-induced menopausal symptoms ( N=422 ) were r and omly assigned to CBT ( n=109 ) , PE ( n=104 ) , CBT/PE ( n=106 ) , or to a waiting list control group ( n=103 ) . Self-report question naires were completed at baseline , 12 weeks , and 6 months . Multilevel procedures were used to compare the intervention groups with the control group over time . RESULTS Compared with the control group , the intervention groups had a significant decrease in levels of endocrine symptoms ( Functional Assessment of Cancer Therapy-Endocrine Symptoms ; P<.001 ; effect size , 0.31 - 0.52 ) and urinary symptoms ( Bristol Female Lower Urinary Tract Symptoms Question naire ; P=.002 ; effect size , 0.29 - 0.33 ) , and they showed an improvement in physical functioning ( 36-Item Short Form Health Survey physical functioning subscale ; P=.002 ; effect size , 0.37 - 0.46 ) . The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats ( problem rating scale of the Hot Flush Rating Scale ; P<.001 ; effect size , 0.39 - 0.56 ) and an increase in sexual activity ( Sexual Activity Question naire habit subscale ; P=.027 ; effect size , 0.65 ) . Most of these effects were observed at both the 12-week and 6-month follow-ups . CONCLUSION CBT and PE can have salutary effects on endocrine symptoms and , to a lesser degree , on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause . Future work is needed to improve the design and the planning of these interventions to improve program adherence OBJECTIVE : Several clinical studies suggest that black cohosh may be effective in climacteric complaints . However , evidence of its efficacy based on current quality st and ards has been limited . METHODS : This r and omized , multicenter , double-blind clinical trial compared the efficacy and tolerability of the isopropanolic black cohosh extract in the treatment of climacteric complaints compared with placebo . A total of 304 patients were r and omly allocated to receive tablets corresponding to 40 mg drug or matching placebo daily for 12 weeks . The primary efficacy measure was the change from baseline on the Menopause Rating Scale I ; secondary measures included changes in its subscores and safety variables . RESULTS : Patient groups did not differ in baseline characteristics . The isopropanolic black cohosh extract was more effective than placebo ( P < .001 ) depending on time from symptom onset ( P = .014 ) and follicle-stimulating hormone level ( P = .011 ) . The effect size was 0.03 to 0.05 Menopause Rating Scale units which is similar to recent hormone replacement therapy study results ( 0.036 Menopause Rating Scale units ) and may therefore be considered clinical ly relevant . Women in the early climacteric phase benefited more than in the late phase . The hot flush subscore was the most effective measure of the isopropanolic black cohosh extract 's efficacy . There were no relevant group differences in adverse events , laboratory findings , or tolerability . CONCLUSION : This isopropanolic extract of black cohosh root stock is effective in relieving climacteric symptoms , especially in early climacteric women . LEVEL OF EVIDENCE : Objective The aim of this study was to investigate the potential effects of pomegranate seed oil ( PGS ) on menopausal symptoms . Methods The prospect i ve r and omized , placebo-controlled , double-blinded trial was completed by 81 postmenopausal women , who received two daily doses of either 30 mg PGS containing 127 & mgr;g of steroidal phytoestrogens per dose or a placebo for 12 weeks . The participants reported their number of hot flashes and completed the Menopause Rating Scale II at baseline and at weeks 4 , 8 , 12 , and 24 . At baseline and after 12 weeks , hormonal status was determined . Results After 12 weeks of treatment , PGS reduced the number of hot flashes per day by 4.3 ( 38.7 % ) , whereas placebo reduced it by 2.5 ( 25.6 % ) . Both groups were significant compared with baseline , but the treated group was not significant compared with the placebo group ( P = 0.17 ) . After 24 weeks , the treated group showed a mean of 7.1 ( interquartile range , 4.0 ) hot flashes per day compared with the placebo group with a mean of 8.8 ( interquartile range , 5.0 ; P = 0.02 ) . Although the overall sum score of the Menopause Rating Scale II parameters at week 12 decreased in the treated group from 16.0 to 9.0 at week 12 and in the placebo group from 18.0 to 14.5 ( P = 0.08 ) , the sum score of the vegetative somatic symptoms subgroup decreased strongly versus placebo ( P < 0.03 ) , attributable mainly to an improvement in sleeping disorders . PGS did not affect the hormone status , and no adverse effects were reported . Conclusions In postmenopausal women , PGS does not significantly reduce hot flashes within a 12-week observation period , but further studies are needed to investigate the long-term effect IMPORTANCE Estrogen therapy is the gold st and ard treatment for hot flashes and night sweats , but some women are unable or unwilling to use it because of associated risks . The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment . While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen , these medications have not been simultaneously evaluated in one clinical trial to date . OBJECTIVE To determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms ( VMS ) . DESIGN , SETTING , AND PARTICIPANTS In total , 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day ( mean , 8.1 per day ) were recruited from the community to MsFLASH ( Menopause Strategies : Finding Lasting Answers for Symptoms and Health ) clinical network sites between December 5 , 2011 , and October 15 , 2012 . INTERVENTIONS Participants were r and omized to double-blind treatment with low-dose oral 17β-estradiol ( 0.5 mg/d ) ( n = 97 ) , low-dose venlafaxine hydrochloride extended release ( 75 mg/d ) ( n = 96 ) , or placebo ( n = 146 ) for 8 weeks . MAIN OUTCOMES AND MEASURES The primary outcome was the mean daily frequency of VMS after 8 weeks of treatment . Secondary outcomes were VMS severity , bother , and interference with daily life . Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments . RESULTS Compared with baseline , the mean VMS frequency at week 8 decreased to 3.9 ( 95 % CI , 2.9 - 4.9 ) VMS per day ( 52.9 % reduction ) in the estradiol group , to 4.4 ( 95 % CI , 3.5 - 5.3 ) VMS per day ( 47.6 % reduction ) in the venlafaxine group , and to 5.5 ( 95 % CI , 4.7 - 6.3 ) VMS per day ( 28.6 % reduction ) in the placebo group . Estradiol reduced the frequency of symptoms by 2.3 more per day than placebo ( P < .001 ) , and venlafaxine reduced the frequency of symptoms by 1.8 more per day than placebo ( P = .005 ) . The results were consistent for VMS severity , bother , and interference . Low-dose estradiol reduced the frequency of symptoms by 0.6 more per day than venlafaxine ( P = .09 ) . Treatment satisfaction was highest ( 70.3 % ) for estradiol ( P < .001 vs placebo ) , lowest ( 38.4 % ) for placebo , and intermediate ( 51.1 % ) for venlafaxine ( P = .06 vs placebo ) . Both interventions were well tolerated . CONCLUSIONS AND RELEVANCE Low-dose oral estradiol and venlafaxine are effective treatments for VMS in women during midlife . While the efficacy of low-dose estradiol may be slightly superior to that of venlafaxine , the difference is small and of uncertain clinical relevance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01418209 OBJECTIVE To investigate the efficacy and tolerability of a new 7-day transdermal sequential estradiol/levonorgestrel patch ( Fem7 Combi ; Merck KGaA ; Germany ) , versus placebo , as hormone replacement therapy in menopausal women . METHODS A multicentre , r and omized , clinical study consisting of a 3-week screening phase , a 12-week double-blind , placebo-controlled treatment phase , and a 12-week open , follow-up phase . Women aged 40 - 65 years with an intact uterus and menopausal complaints were r and omized to either 2 weeks of an estradiol mono patch ( 50 microg per 24 h ) followed by 2 weeks of an estradiol/levonorgestrel combination patch ( 50 microg/10 microg per 24 h ) , or a placebo patch , for three 28-day cycles . Changes in the Kupperman Index and the frequency of hot flushes were assessed . RESULTS The sequential use of a 7-day estradiol patch and a 7-day estradiol/levonorgestrel patch was superior to placebo in reducing menopausal symptoms , and was well tolerated . At the end of the treatment phase , there was a statistically significant reduction in the Kupperman Index score versus placebo ( P<0.0001 ) , and a statistically significant difference between groups in the proportion of patients with a reduction in the number of hot flushes ( at least 50 % versus baseline ) . During the open follow-up phase , there was a marked reduction in the Kupperman Index score and the number of hot flushes for patients switched from placebo to active study medication . The active medication was effective throughout the 1-week application period . CONCLUSIONS The new 7-day transdermal sequential estradiol/levonorgestrel patch was well tolerated , providing rapid and effective relief of menopausal symptoms . The addition of low-dose levonorgestrel did not influence the beneficial effects of estradiol New estradiol ( E2 ) transdermal matrix patches developed for once-a-week application , releasing 25 μg E2 ( 7D-25 ) or 50 μg E2 ( 7D-50 ) daily , were investigated in comparison with a placebo patch and the twice-weekly parent patch releasing 50 μg E2 ( Derm-50 ) daily . Three hundred and eleven postmenopausal patients suffering at least seven hot flushes daily were r and omly assigned to the four parallel groups and treated continuously for 12 weeks without progestin opposition . The daily number of hot flushes significantly decreased in all groups . At the 12th week the decrease from a baseline average of eight to nine episodes per day was 78 % with 7D-25 , 93 % and 97 % respectively with 7D-50 and Derm-50 , and significantly ( p < 0.001 ) lower with placebo ( 59 % ) . Comparable efficacy was observed in terms of severity of hot flushes , Kupperman Index and patient self-rated overall efficacy . Minor systemic adverse events occurred in 10.0 % , 8.8 % , 16.9 % ) and 13.5 % patients in the placebo , 7D-25 , 7D-50 and Derm-50 groups respectively . Occasional mild and transient itching and /or erythema at the site of application was reported by a few patients , with no difference between groups or between once-weekly or twice-weekly application . In conclusion all E2 patches were significantly more effective than placebo in relieving climacteric symptoms in a dose-dependent fashion and all were well tolerated Abstract Objective : To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause . Design : R and omised , double blind , placebo controlled study . Setting : District general hospital and teaching hospital . Subjects : 56 menopausal women suffering hot flushes at least three times a day . Intervention : Four capsules twice a day of 500 mg evening primrose oil with 10 mg natural vitamin E or 500 mg liquid paraffin for six months . Main outcome measures - Change in the number of hot flushes or sweating episodes a month . Results : 56 diaries were analysed , 28 from women taking gamolenic acid and 28 from those taking placebo . Only 18 women given gamolenic acid and 17 given placebo completed the trial . The mean ( SE ) improvement in the number of flushes in the last available treatment cycle compared with the control cycle was 1.9 ( 0.4 ) ( P<0.001 ) for daytime flushes and 0.7 ( 0.3 ) ( P<0.05 ) for night time flushes in womentaking placebo ; the corresponding values for women taking gamolenic acid were 0.5 ( 0.4 ) and 0.5 ( 0.3 ) . In women taking gamolenic acid the only significant improvement was a deduction in the maximum number of night time flushes ( 1.4 ( 0.6 ) ; P<0.05 ) . Conclusion : Gamolenic acid offers no benefit over placebo in treating menopausal flushing OBJECTIVES Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women . The primary aim of this double-blind , multi-centre , r and omised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone . STUDY DESIGN 313 women with ≥50 moderate to severe hot flushes during the previous week were r and omised to 0.5 mg 17β-oestradiol/2.5 mg dydrogesterone ( E 0.5 mg/D 2.5 mg ) , 1 mg 17β-oestradiol/5 mg dydrogesterone ( E 1mg/D 5 mg ) or placebo for 13 weeks . The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks , whilst the other groups continued on the same treatment . RESULTS After 13 weeks , the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group ( -6.4 vs. -4.9 , p<0.001 ) and comparable to that in the 1/5 mg group ( -6.3 ) . E 0.5 mg/D 2.5 mg and E 1mg/D 5 mg significantly improved the total Menopause Rating Scale score . The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg . The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81 % ; this increased to 91 % in months 10 - 12 . CONCLUSIONS Continuous combined 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life , and was associated with a high amenorrhoea rate and a good tolerability profile Objective To evaluate the efficacy of two ultra-low-dose 17β-estradiol plus norethisterone acetate ( NETA ) treatment regimens for relieving menopausal symptoms . Design A total of 577 postmenopausal women were enrolled , in three treatment groups in a double-blind , r and omized , placebo-controlled study of 0.5 mg 17β-estradiol + 0.1 mg NETA or 0.5 mg 17β-estradiol + 0.25 mg NETA or placebo . Participants returned at weeks 4 , 8 , 12 and 24 for climacteric complaint evaluation based on a daily diary vasomotor symptom record . Patients were assessed by the Greene Climacteric Scale and urogenital symptoms were also evaluated . Results Treatment with ultra-low-dose 0.5 mg 17β-estradiol + 0.1 mg NETA ( 0.1 Group ) or 0.5 mg 17β-estradiol + 0.25 mg NETA ( 0.25 Group ) effectively reduced the severity and number of hot flushes within the initial weeks of therapy . Compared to placebo , a rapid , statistically significant decrease in the frequency and severity of hot flushes was achieved by week 3 , followed by further improvement which continued throughout the study . There were no statistically significant differences between the active treatment arms . Conclusions The data show that both ultra-low-dose regimens are effective in reducing the severity and number of hot flushes compared to placebo , with good safety profiles Summary Background Hot flushes affect 70 % of menopausal women and often severely impact physical , psychosocial , sexual , and overall wellbeing . Hormone replacement therapy is effective but is not without risk . Neurokinin B signalling is increased in menopausal women , and has been implicated as an important mediator of hot flushes . Methods This phase 2 , r and omised , double-blind , placebo-controlled , single-centre , crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist ( MLE4901 ) on menopausal hot flushes . Eligible participants were healthy women aged 40–62 years , having seven or more hot flushes in every 24 h of which some were reported as being severe or bothersome , who had not had a menstrual period for at least 12 months , and who had not been taking any medication shown to improve menopausal flushes in the preceding 8 weeks . Participants received 4 weeks of MLE4901 ( 40 mg , orally , twice daily ) and placebo ( orally , twice daily ) in r and om order separated by a 2 week washout period . R and omisation was completed by a central computer , and participants were allocated to treatment number in numerical order . The primary outcome was the total number of hot flushes during the final week of both treatment periods . Analyses were by intention to treat and per protocol using generalised linear mixed models and st and ard crossover analysis . All analyses were prespecified in the study protocol . The trial is registered at Clinical Trials.gov , number NCT02668185 . Findings 68 women were screened between Feb 3 and Oct 10 , 2016 , of which 37 were r and omly assigned and included in an intention-to-treat analysis . 28 participants completed the trial and were included in a per- protocol analysis . MLE4901 significantly reduced the total weekly number of hot flushes by 45 percentage points ( 95 % CI 22–67 ) compared with the placebo ( intention-to-treat adjusted means : placebo 49·01 [ 95 % CI 40·81–58·56 ] vs MLE4901 19·35 [ 15·99–23·42 ] ; adjusted estimate of difference 29·66 [ 17·39–42·87 ] , p<0·0001 ) . Treatment was well tolerated . Three participants developed a transaminase rise ( alanine aminotransferase 4·5–5·9 times the upper limit of normal ) with a normal bilirubin 28 days after starting MLE4901 , which normalised within 90 days . Interpretation Treatment with a neurokinin 3 receptor antagonist ( MLE4901 ) could be practice changing as it safely and effectively relieves hot flush symptoms without the need for oestrogen exposure . Larger scale studies of longer duration are now indicated . Funding UK Medical Research Council and National Institute for Health Research Objective : This study aims to evaluate the effectiveness and safety of Gua sha therapy on perimenopausal symptoms , quality of life , and serum female hormones in participants with perimenopausal syndrome . Methods : A prospect i ve , r and omized , controlled clinical trial was conducted at the First Affiliated Hospital of Nanjing University of Chinese Medicine in China . Eighty women with perimenopausal syndrome were recruited and r and omized into an intervention group or a control group . Participants in the intervention group received 15-minute Gua sha treatment sessions once a week plus conventional treatment for 8 weeks , whereas participants in the control group received conventional treatment alone . The primary outcome was the change in perimenopausal symptoms and quality of life as obtained through the modified Kupperman Index ( KI ) and the Menopause-Specific Quality of Life . The secondary outcome was the change of serum female hormones including estrogen , follicle-stimulating hormone , and luteinizing hormone . Results : Seventy-five out of 80 participants ( 93.8 % ) completed the study —38 in the intervention group and 37 in the control group . The baseline levels of demographic and outcome measurements were comparable between the two groups . After eight sessions of intervention , the reduction in the total modified KI score was , however , 16.32 ± 4.38 in the intervention group and 11.46 ± 5.96 in the control group , with a difference of 4.86 ± 6.15 ( P < 0.01 ) between the two groups . Also the reductions of hot flash/sweating , paresthesia , insomnia , nervousness , melancholia , fatigue , and headache were greater in the intervention group than in the control group ( P < 0.05 ) . The reduction in the total Menopause-Specific Quality of Life score was 17.87 ± 3.84 in the intervention group and 13.62 ± 7.40 in the control group , with a difference of 4.46 ± 7.52 ( P < 0.01 ) between the two groups . And the scores for vasomotor , psychosocial , and physical domains in the intervention group were significantly lower than those in the control group ( P < 0.05 ) . There were no significant differences in serum estrogen , follicle-stimulating hormone , and luteinizing hormone between the two groups . Conclusions : The results of this study suggest that Gua sha therapy was effective and safe in relieving perimenopausal symptoms and improving the quality of life in participants with perimenopausal syndrome . The therapy may serve as a promising , effective , nondrug treatment for perimenopausal syndrome in clinical work . Additional research is needed to better underst and its effectiveness and examine its mechanism for treating perimenopausal syndrome Objective : The aim of the study was to examine the efficacy of an unguided , self-help cognitive behavior therapy ( SH-CBT ) booklet on hot flush and night sweat ( HFNS ) problem rating , delivered in a work setting . Methods : Women aged 45 to 60 years , having 10 or more problematic HFNS a week , were recruited to a multicenter r and omized controlled trial , via the occupational health/human re sources departments of eight organizations . Participants were 1:1 r and omized to SH-CBT or no treatment waitlist control ( NTWC ) . The primary outcome was HFNS problem rating ; secondary outcomes included HFNS frequency , work and social adjustment , sleep , mood , beliefs and behaviors , and work-related variables ( absence , performance , turnover intention , and work impairment due to presenteeism ) . Intention-to-treat analysis was used , and between-group differences estimated using linear mixed models . Results : A total of 124 women were r and omly allocated to SH-CBT ( n = 60 ) and NTWC ( n = 64 ) . 104 ( 84 % ) were assessed for primary outcome at 6 weeks and 102 ( 82 % ) at 20 weeks . SH-CBT significantly reduced HFNS problem rating at 6 weeks ( SH-CBT vs NTWC adjusted mean difference , −1.49 ; 95 % CI , −2.11 to −0.86 ; P < 0.001 ) and at 20 weeks ( −1.09 ; 95 % CI , −1.87 to −0.31 ; P < 0.01 ) . SH-CBT also significantly reduced HFNS frequency , improved work and social adjustment ; sleep , menopause beliefs , HFNS beliefs/behaviors at 6 and 20 weeks ; improved wellbeing and somatic symptoms and reduced work impairment due to menopause-related presenteeism at 20 weeks , compared with the NTWC . There was no difference between groups in other work-related outcomes . Conclusions : A brief , unguided SH-CBT booklet is a potentially effective management option for working women experiencing problematic HFNS Objectives : To conduct psychometric analyses to condense the Hot Flash-Related Daily Interference Scale ( HFRDIS ) into a shorter form termed the Hot Flash Interference ( HFI ) scale ; evaluate cut-points for both scales ; and establish minimally important differences ( MIDs ) for both scales . Methods : We analyzed baseline and postr and omization patient-reported data pooled across three r and omized trials aim ed at reducing vasomotor symptoms ( VMS ) in 899 midlife women . Trials were conducted across five MsFLASH clinical sites between July 2009 and October 2012 . We eliminated HFRDIS items based on experts ’ content validity ratings and confirmatory factor analysis , and evaluated cut-points and established MIDs by mapping HFRDIS and HFI to other measures . Results : The three-item HFI ( interference with sleep , mood , and concentration ) demonstrated strong internal consistency ( alphas of 0.830 and 0.856 ) , showed good fit to the unidimensional “ hot flash interference factor , ” and strong convergent validity with HFRDIS scores , diary VMS , and menopausal quality of life . For both scales , cut-points of mild ( 0 - 3.9 ) , moderate ( 4 - 6.9 ) , and severe ( 7 - 10 ) interference were associated with increasing diary VMS ratings , sleep , and anxiety . The average MID was 1.66 for the HFRDIS and 2.34 for the HFI . Conclusions : The HFI is a brief assessment of VMS interference and will be useful in busy clinics to st and ardize VMS assessment or in research studies where response burden may be an issue . The scale cut-points and MIDs should prove useful in targeting those most in need of treatment , monitoring treatment response , and interpreting existing and future research findings OBJECTIVE This study compared the effects of a continuous-combined regimen of low-dose hormone therapy ( LD-HT ) versus tibolone and supplemental calcium/vitamin D3 ( control ) on quality of life ( QoL ) in symptomatic postmenopausal women . DESIGN This study was a prospect i ve , r and omised , double-blind , comparative trial with a control group . SETTING The study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora , Brazil . POPULATION A total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited . These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy . INTERVENTIONS The patients were r and omised into three groups : ( 1 ) daily treatment with 2.5 mg tibolone ( n=64 ) , ( 2 ) 50 mg calcium carbonate+200 IU vitamin D3 ( Ca/Vit D3 , n=54 ) or ( 3 ) 1 mg oestradiol+0.5 mg norethindrone acetate ( E2/NETA , n=56 ) for 12 weeks . PRIMARY OUTCOME MEASURES The primary outcome was the evaluation of QoL using the Women 's Health Question naire ( WHQ ) in all subjects at baseline and after 4 , 8 and 12 weeks of treatment . RESULTS A total of 130 women in the following groups completed the study : tibolone ( n=42 ) , Ca/Vit D3 ( n=44 ) and E2/NETA ( n=44 ) . An improved QoL based on the WHQ was observed at T0 ( 80.12±14.04 , 77.73±15.3 , 77.45±15.4 ) and T12 ( 57.0±15.5 , 55.7±16.7 , 58.4±12.6 ) for the tibolone , E2+NETA and Ca/Vit D3 groups , respectively ( p values < 0.05 ) . The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms . The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups ( 4.2±26 , 5.6±2.8 , 5.4±2.8 , respectively , p values < 0.05 ) . LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms ( 3.2±1.5 , 4.0±1.8 , 4.3±2.0 , respectively , p values < 0.05 ) . Adverse effects were few and mild . CONCLUSIONS An improved QoL was observed in the three study groups . Tibolone primarily improved sexual function , and E2/NETA exhibited a superior response for vasomotor symptoms OBJECTIVE To evaluate the effect of soy isoflavones on menopausal symptoms in women who do and who do not produce equol , a daidzein metabolite . METHOD A r and omized , double-blind , placebo-controlled clinical trial was conducted over 6 months with 96 healthy menopausal women . After taking take 135 mg of isoflavones daily for 1 week , the women in the study group were assigned to the equol-producing ( EP ) or the non-EP group according to the presence or absence of equol in their urine . Menopausal symptoms were evaluated using a modified Kupperman Index . RESULT Compared with the placebo group , the scores for hot flashes and excessive sweating were significantly reduced after 3 months , and the scores for weakness , palpitations , limb paresthesia , and total symptoms after 6 months , in the EP group only . CONCLUSIONS Isoflavone supplementation improves menopausal symptoms only in women with the ability to produce equol Objective The aim of this study was to evaluate the effects of a constant-estrogen , intermittent-progestogen hormone replacement regimen ( Ortho-Prefest , Ortho-McNeil Pharmaceutical , Raritan , NJ , USA ) on menopausal symptoms measured by the Kupperman Index and on quality of life measured by the Menopause Quality of Life-Intervention question naire . Design This was a r and omized , double-blind , placebo-controlled multicenter study of 90 days ' duration . Nonhysterectomized , postmenopausal women with vasomotor symptoms and at least 6 months ' amenorrhea were eligible . On completion of the placebo-controlled portion of the study , participants could elect to receive active treatment for an additional 90 days . Results The study enrolled 119 participants , 59 and 60 in the Prefest and placebo groups , respectively . A marked reduction of menopausal symptoms , as measured by the Kupperman Index , was observed in the active treatment group compared with the placebo group after 45 days ' treatment ( mean reduction , 14.8 v 7.2 points , respectively ) , which was sustained to day 90 ( 16.8 v 7.8 points;P < 0.001 ) . Similarly , greater improvement in quality of life , as measured by the Menopause Quality of Life summary score , was also observed in the active treatment group for the same period ( improvement of up to 1.6 points v 0.7 points;P < 0.001 ) . The adverse event profile was unremarkable . Of the 114 participants who received the active treatment , 6 withdrew because of adverse events . Conclusions The constant-estrogen , intermittent-progestogen regimen was highly effective in relieving menopausal symptoms and in improving quality of life and was well received by the study participants Objectives To investigate two different doses of oral estradiol to reduce the number of hot flushes in Japanese women with climacteric symptoms . Methods Women ( n = 211 ) aged 40–64 years who had experienced natural menopause or bilateral oophorectomy , with ≥ three moderate/severe hot flushes per day in the week before study , were r and omized to receive micronized estradiol ( E2 ) 0.5 or 1.0 mg or placebo once daily for 8 weeks . The primary efficacy endpoint was percentage change in mean daily number of hot flushes over 7 days from baseline to final examination . Results Percentage change in mean daily number of hot flushes at final examination was similar for E2 0.5 mg and E2 1.0 mg ( −79.58 ± 28.29 % vs. −82.49 ± 25.31 % , p = 0.555 ) but was significantly lower with placebo ( −57.89 ± 34.15 % , p < 0.001 vs. E2 , both doses ) . There was no significant difference in number of treatment-related adverse events occurring in the E2 0.5 and 1.0 mg groups ( 25 % and 36.6 % , respectively ) . The higher E2 dose showed more pronounced effects on symptom severity . Conclusions The dose of 0.5 mg/day was effective as the oral E2 starting dose for treatment of hot flushes in Japanese women PURPOSE Hot flashes are a common problem for which effective and safe treatments are needed . The current trial was conducted on the basis of preliminary promising data that pregabalin decreased hot flashes . PATIENTS AND METHODS A double-blind , placebo-controlled , r and omized trial design was used to compare pregabalin at target doses of 75 mg twice daily and 150 mg twice daily with a placebo . Hot flash frequencies and scores ( frequency times mean severity ) were recorded daily during a baseline week and for six treatment weeks . The primary end point for this study was the change-from-baseline hot flash score during treatment week 6 between the 150 mg twice daily target pregabalin treatment and placebo . Nonparametric Wilcoxon rank sum tests , two- sample t tests , and chi(2 ) tests were used to compare the primary and secondary hot flash efficacy end points between pregabalin treatments and placebo . RESULTS Hot flash score changes available for 163 patients during the sixth treatment week compared with a baseline week decreased by 50 % , 65 % , and 71 % in the placebo , and target 75 mg twice daily and 150 mg twice daily pregabalin arms , respectively ( P = .009 and P = .007 , comparing respective pregabalin arms to the placebo arm ) . While some toxicities were significantly more common in the pregabalin arms , being more evident with the higher dose , pregabalin was generally well tolerated by most patients . CONCLUSION Pregabalin decreases hot flashes and is reasonably well tolerated . A target dose of 75 mg twice daily is recommended . Its effects appear to be roughly comparable to what has been reported with gabapentin and with some newer antidepressants Objectives Drospirenone is a novel progestogen that , combined with 17β-estradiol , reduces the frequency and severity of menopausal vasomotor symptoms ( VMS ) in different population s. This double-blind , multicenter study compared the efficacy , safety and tolerability of 2 mg drospirenone/1 mg estradiol ( DRSP/E2 ) vs. placebo in Chinese postmenopausal women with moderate to severe VMS . Methods Women , aged 45–65 years , were r and omized to DRSP/E2 ( n = 183 ) or placebo ( n = 61 ) once daily for four 28-day cycles . Changes in the frequency and severity of hot flushes were analyzed as primary variables , together with other climacteric and urogenital symptoms , clinical global improvement , adverse events and physical/gynecological parameters . Results Relative changes in numbers of hot flushes/week were −80.4 % for DRSP/E2 vs. −51.9 % for placebo ( treatment difference −28.5 % , p < 0.0001 ) . There were trends toward a greater reduction in severity of hot flushes with DRSP/E2 treatment . Patients treated with DRSP/E2 were more often free from sweating episodes ( p < 0.0001 ) and vaginal dryness ( p = 0.0008 ) . Other climacteric symptoms , including nervousness and pollakisuria , followed a trend of greater response with DRSP/E2 . Similar to other combination HRT regimens , DRSP/E2 increased occurrences of bleeding , but these decreased over time . Adverse events in patients treated with DRSP/E2 were mostly mild to moderate and withdrawal rates were low . Conclusions Daily treatment of postmenopausal Chinese women with DRSP/E2 for 16 weeks significantly reduced the incidence of hot flushes and demonstrated advantages vs. placebo for other climacteric symptoms . These results indicate that DRSP/E2 is effective , safe and well tolerated in postmenopausal Chinese women OBJECTIVE The objective of the study was to assess the efficacy and safety of desvenlafaxine ( administered as desvenlafaxine succinate ) for the treatment of vasomotor symptoms . STUDY DESIGN This was a 26 week , double-blind , placebo-controlled trial of 567 postmenopausal women ( mean age , 53.7 years ; time since natural menopause , 4.8 years ) experiencing 50 or more hot flushes ( HFs ) per week , r and omly assigned to desvenlafaxine ( 100 or 150 mg ) or placebo . Change from baseline in average daily number of moderate to severe HFs and average daily HF severity were compared with placebo at weeks 4 , 12 , and 26 . RESULTS A significantly greater decrease from baseline in number of HFs occurred at weeks 4 and 12 with 100 and 150 mg desvenlafaxine compared with placebo ( week 12 reductions : 60 % , 66 % , and 47 % , respectively ; all P < or = .002 ) . Only the 150 mg dose showed significant improvement from baseline at 26 weeks compared with placebo ( week 26 reductions : 61 % , 69 % , and 51 % , respectively ) , although the study was not powered to demonstrate efficacy beyond the initial 12 weeks of therapy . The average daily severity decreased significantly more at weeks 4 and 12 with desvenlafaxine compared with placebo ( all P < or = .002 ) . Significantly more desvenlafaxine-treated subjects than placebo-treated subjects discontinued because of adverse events during week 1 only . CONCLUSION Desvenlafaxine is an effective treatment for menopausal HFs Background Awareness of the risks associated with hormone therapy for menopausal symptoms has sparked a global decline in this treatment . Alternative treatments to relieve menopausal symptoms are therefore required . The applied relaxation ( AR ) technique has proven to be successful for symptom amelioration , but requires participation in 12 weekly classes . The purpose of this study was to determine the effectiveness of a modified relaxation version ( MR ) of AR for treatment of hot flashes , night sweats , and sleep disturbances . Methods We conducted a12-week , r and omized , parallel , open-label , controlled trial in perimenopausal and postmenopausal women visiting the menopausal clinic . Participants were r and omly assigned to an MR or AR group . The MR group ( n=36 ) received a single session of ( MR ) training and the AR group ( n=35 ) received conventional 12-week training . Participants were instructed to practice the techniques daily at home for 12 weeks . The main outcome was the measure on the severity scale and frequency of hot flashes , night sweats , and sleep disturbances . Results All participants completed the study . Total severity scores in both groups decreased after 12 weeks , but there was no difference between the groups ( P=0.93 ) . The severity score for hot flashes in the MR group decreased more than in the AR group ( P=0.02 ) . The severity scores for night sweats and sleep disturbances decreased in both groups . The frequency of hot flashes , night sweats , and sleep disturbances were also decreased in both groups . Conclusion A shorter , modified version of the AR was equally effective or slightly better than the conventional AR for the relief of hot flashes , night sweats , and sleep disturbances in perimenopausal and postmenopausal women . Recommendations for future research include confirmatory studies and trials with larger sample Abstract Objective : To analyze the short-term efficacy and safety over menopausal symptoms of three low-dose continuous sequential 17β-estradiol (E)/progesterone ( P ) parental monthly formulations using novel non-polymeric microspheres . Methods : This was a multicenter , r and omized , single blinded study in which peri- and postmenopausal women were assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P ( Group A , n = 34 ) , 1 mg E + 20 mg P ( Group B , n = 24 ) or 1 mg E + 30 mg P ( Group C , n = 26 ) for 6 months . Primary efficacy endpoints included mean change in the frequency and severity of hot flushes and the effect over urogenital atrophy symptoms at 3 and 6 months . Safety variables included changes in the rate of amenorrhea , endometrial thickness and histopathology , and local and systemic adverse events . Results : Compared to baseline at month 6 , the three treatment schemes significantly decreased the rate of urogenital atrophy symptoms and the frequency ( mean number per day ) and severity ( mean number grade d as moderate and severe per month ) of hot flushes . No differences in studied efficacy parameters were observed between studied groups at baseline or at the end of the study . For all groups the most frequent adverse event was pain at the injection site ; however they were all rated as mild . At the end of the study peri- and postmenopausal women displayed no significant changes in endometrial thickness or histopathology in all treated groups . The rate of amenorrhea at the end of the study decreased for all studied groups yet was less evident among postmenopausal women as compared to perimenopausal ones . Conclusions : The three low-dose continuous sequential intramuscular monthly treatments of E/P using novel microsphere technology were effective at reducing menopausal symptoms at short-term with a low rate of adverse events . More long-term and comparative research is warranted to support our positive findings Objective This study aims to investigate the efficacy and safety of daily drospirenone/17&bgr;-estradiol in two low-dose combinations ( 0.25 mg/0.5 mg and 0.5 mg/0.5 mg , respectively ) versus 17&bgr;-estradiol ( 0.3 mg ) or placebo in postmenopausal women with moderate to severe vasomotor symptoms . Methods Seven hundred thirty-five postmenopausal women aged 40 years or older who experienced a minimum of 7 to 8 moderate to severe hot flushes per day , or 50 to 60 moderate to severe hot flushes per week , participated in a 12-week , double-blind , r and omized , placebo-controlled study . The primary efficacy variables were mean changes from baseline to weeks 4 and 12 in the weekly frequency and weekly mean daily severity of moderate to severe hot flushes recorded daily by the participants on diary cards . Results All active treatments were significantly more effective than placebo for the primary efficacy variables for drospirenone/17&bgr;-estradiol ( P < 0.0001 ) , and for 17&bgr;-estradiol ( P < 0.01 ) at 4 and 12 weeks . Efficacy was greater for both low-dose drospirenone/17&bgr;-estradiol combinations versus the lower-dose 17&bgr;-estradiol . Change in vaginal pH and vaginal maturation index showed significant improvements ( with P values versus placebo of < 0.0001 and P ⩽ 0.0028 , respectively ) , and exploratory analysis of the Clinical Global Impressions scale score indicated an overall satisfaction of women with active treatments . All active treatments were generally well tolerated with low rates of adverse event – related dropouts , and the safety profile of drospirenone/17&bgr;-estradiol in both low-dose combinations was consistent with previous studies . Conclusions Drospirenone 0.25 mg/17&bgr;-estradiol 0.5 mg is concluded to be the lowest dose with demonstrated efficacy in the treatment of postmenopausal women with moderate to severe vasomotor symptoms Summary Background Hot flushes and night sweats ( HFNS ) affect 65–85 % of women after breast cancer treatment ; they are distressing , causing sleep problems and decreased quality of life . Hormone replacement therapy is often either undesirable or contraindicated . Safe , effective non-hormonal treatments are needed . We investigated whether cognitive behavioural therapy ( CBT ) can help breast cancer survivors to effectively manage HFNS . Methods In this r and omised controlled trial , we recruited women from breast clinics in London , UK , who had problematic HFNS ( minimum ten problematic episodes a week ) after breast-cancer treatment . Participants were r and omly allocated to receive either usual care or usual care plus group CBT ( 1:1 ) . R and omisation was done in blocks of 12–20 participants , stratifying by age ( younger than 50 years , 50 years or older ) , and was done with a computer-generated sequence . The trial statistician and research ers collecting outcome measures were masked to group allocation . Group CBT comprised one 90 min session a week for 6 weeks , and included psycho-education , paced breathing , and cognitive and behavioural strategies to manage HFNS . Assessment s were done at baseline , 9 weeks , and 26 weeks after r and omisation . The primary outcome was the adjusted mean difference in HFNS problem rating ( 1–10 ) between CBT and usual care groups at 9 weeks after r and omisation . Analysis of the primary endpoint was done by modified intention to treat . The trial is registered , IS RCT N13771934 , and was closed March 15 , 2011 . Findings Between May 5 , 2009 , and Aug 27 , 2010 , 96 women were r and omly allocated to group CBT ( n=47 ) or usual care ( n=49 ) . Group CBT significantly reduced HFNS problem rating at 9 weeks after r and omisation compared with usual care ( mean difference −1·67 , 95 % CI −2·43 to −0·91 ; p<0·0001 ) and improvements were maintained at 26 weeks ( mean difference −1·76 , −2·54 to −0·99 ; p<0·0001 ) . We recorded no CBT-related adverse events . Interpretation Group CBT seems to be a safe and effective treatment for women who have problematic HFNS after breast cancer treatment with additional benefits to mood , sleep , and quality of life . The treatment could be incorporated into breast cancer survivorship programmes and delivered by trained breast cancer nurses . Funding Cancer Research UK AIM The aim of the present study was to assess the efficacy and safety of a st and ardized compound based on an extract of soy phytoestrogens , with high doses of isoflavones in the management of menopausal hot flushes . METHODS A total of 180 women aged 40 - 65 years with a minimum of five moderate-to-severe hot flushes in the last 7 days at baseline and absence of menstruation for at least 6 months participated in a 12-week prospect i ve , r and omized , double-blind , placebo-controlled multicenter trial . After a 2-week run-in period , women received one tablet a day of 80 mg isoflavones ( corresponding to 60 mg of genistein ) or a matching placebo . RESULTS The mean daily number of moderate-to-severe hot flushes decreased in both study groups , but the reduction was greater in the isoflavones arm at 6 ( 36.2 % ) and 12 weeks ( 41.2 % ) than in the placebo arm ( 24.0 % at 6 weeks , 29.3 % at 12 weeks ) , with a difference of 1.1 ( 95 % CI [ -2.0 to -0.06 ] ) ( P = 0.038 ) at 6 weeks and 1.1 ( 95 % CI [ -2.05 to -0.15 ] ) ( P = 0.023 ) at 12 weeks . Similar findings were obtained for hot flushes of any intensity . The Kupperman index decreased in both study groups . Relief of hot flushes was greater when time to menopause was > or=12 months and in cases of BMI > or=27 kg/m(2 ) . CONCLUSION In daily practice conditions , high doses of isoflavones , particularly genistein , can be used for the management of hot flushes in postmenopausal women not treated with hormone replacement therapy due to their superior efficacy to placebo and very good safety profile Objective : The aim of this study was to investigate whether tapering down of combined estrogen plus progestogen therapy ( EPT ) reduced the recurrence of hot flashes and resumption of therapy compared with abrupt discontinuation . A secondary aim was to evaluate whether health-related quality of life ( HRQoL ) was affected after discontinuation of EPT and to investigate the possible factors predicting resumption of EPT . Methods : Eighty-one postmenopausal women undergoing EPT because of hot flashes were r and omized to tapering down or abrupt discontinuation of EPT . Vasomotor symptoms were recorded in self-registered diaries , and resumption of hormone therapy ( HT ) was asked for at every follow-up . The Psychological General Well-being Index was used to assess HRQoL. Results : Neither the number nor the severity of hot flashes or HRQoL or frequency of resumption of HT differed between the two modes of discontinuation of EPT during up to 12 months of follow-up . About every other woman had resumed HT within 1 year . Women who resumed HT after 4 or 12 months reported more deteriorated HRQoL and more severe hot flashes after discontinuation of therapy than did women who did not resume HT . Conclusions : Women who initiate EPT because of hot flashes may experience recurrence of vasomotor symptoms and impaired HRQoL after discontinuation of EPT regardless of the discontinuation method used , abrupt or taper down . Because , in addition to severity of flashes , decreased well-being was the main predictor of the risk to resume HT , it seems important to also discuss quality of life in parallel with efforts to discontinue HT Abstract Background and objective . To estimate whether aerobic training has an effect on frequency of hot flushes or quality of life . Design . A r and omized controlled trial . Participants and setting . Symptomatic , sedentary women ( n = 176 ) , 43–63 years , no current use of hormone therapy . Intervention . Unsupervised aerobic training for 50 minutes four times per week during 6 months . Outcomes . Hot flushes as measured with Women 's Health Question naire ( WHQ ) and Health-Related Quality of Life ( HRQoL , SF-36 ) , daily reported hot flushes on phone-based diary , cardiorespiratory fitness ( CRF ) , and body composition . Results . Intervention group had larger decrease in the frequency of night-time hot flushes based on phone diary ( P for month × group = 0.012 ) , but not on WHQ scale . Intervention group had less depressed mood ( P = 0.01 ) than control women according to change in WHQ score . Changes in WHQ score in depressed mood ( P = 0.03 ) and menstrual symptoms ( P = 0.01 ) in the intervention group were significantly dependent on frequency of training sessions . HRQoL was improved among the intervention group women in physical functioning ( P = 0.049 ) and physical role limitation ( P = 0.017 ) . CRF improved ( P = 0.008 ) , and lean muscle mass increased ( P = 0.046 ) significantly in the intervention group as compared to controls . Conclusions . Aerobic training may decrease the frequency of hot flushes and improve quality of life among slightly overweight women Objectives To compare the effect of micro-dose transdermal estradiol and placebo on the incidence and severity of menopausal symptoms and well-being in postmenopausal Asian women with vasomotor symptoms . Design Multicenter , double-blind , r and omized , placebo-controlled study . Results Of 165 subjects r and omized to estradiol 0.014 mg/day or placebo for 12 weeks , 80 per group were included in the analysis . Groups were comparable at baseline , although time since menopause was slightly shorter in the estradiol group . There was a greater reduction in mean weekly hot flushes at week 12 in the estradiol group ( 55 % ) than the placebo group ( 40 % ; p < 0.01 ) , which was evident by week 4 . A similar pattern was seen for moderate and severe hot flushes ( −58 % vs. −39 % , respectively ) . Reductions were statistically significant at weeks 4 , 8 , and 12 . Vaginal pH fell significantly in the estradiol group by week 4 and then remained stable throughout the treatment period , but there were no significant changes in the placebo group . Vaginal maturation value increased more in the estradiol than the placebo group ( p < 0.001 ) . Few subjects had vaginal bleeding or spotting . Quality of life improved similarly in both groups . Urogenital symptoms improved considerably from baseline in both treatment groups , with no significant differences . Eight subjects experienced treatment-related adverse events ( seven in the estradiol group ) . Conclusions In Asian women , micro-dose estradiol was significantly superior to placebo in improving vasomotor symptoms . The bleeding profile was comparable with that of placebo . Micro-dose estradiol was safe and well tolerated in Asian women Objective : The aim of this study was to assess the efficacy of TU-025 , keishibukuryogan , a Japanese prescription herbal medicine used for hot flash management , in American women . Methods : This r and omized , double-blind , placebo-controlled , phase II trial enrolled 178 postmenopausal women aged 45 to 58 years with a Mayo hot flash score greater than 28 per week who met other inclusion criteria . After a 1-week placebo run-in period , participants were r and omly assigned placebo , or 7.5 g/day , or 12.5 g/day groups , for 12 weeks . Primary and secondary outcomes were measured using the Mayo Clinic Hot Flash Diary , the Greene Climacteric Index , and the Pittsburgh Sleep Quality Index . Results : At 3 months , hot flash scores , climacteric symptoms , and sleep quality improved by 34 % in the placebo group , 40 % in the 7.5 g/day group , and 38 % in the 12.5 g/day group . ( P < 0.001 ) . However , the differences in changes between groups were not statistically significant ( P = 0.990 ) . Diarrhea unexpectedly developed in 20 % of participants receiving active medication . Conclusions : For American women , unlike the clinical experience for Japanese women , TU-025 did not significantly reduce the frequency and severity of hot flash symptoms , improve climacteric symptoms , or benefit sleep quality . This study identified several potentially significant method ological factors to be considered in future scientific assessment s of traditional Asian medicines OBJECTIVE The efficacy , bleeding patterns , and safety of continuous transdermal and sequential transdermal progestogen therapy were compared with those of oral progestogen therapy in postmenopausal women receiving transdermal estrogen . METHODS In an open-label , 1-year ( 13 treatment periods , 28 days each ) , r and omized study , 774 postmenopausal women were assigned to receive 50 micrograms/day of continuous trans dermal estradiol with either continuous or sequential transdermal norethisterone acetate ( NETA ) in daily doses of 170 or 350 micrograms in a single transdermal patch or sequential oral progestogen ( 1 mg norethisterone [ NET ] or 20 mg dydrogesterone/day ) . RESULTS The average number of hot flushes/day decreased from pre study by over 90 % ( P < .001 ) , and this reduction was unaffected by different progestogen regimens . With sequential progestogen , bleeding incidence and the number of bleeding days did not change over the course of the study but were lower in the low-dose transdermal progestogen group . With continuous progestogen , the incidence of bleeding decreased in both the low- and high-dose groups , from 35 % and 45 % in treatment period 1 to 25 % and 15 % , respectively , at the end of treatment . Adverse event incidence was similar in all groups , with 23 % to 36 % of subjects reporting events possibly or probably related to HRT ( excluding vaginal bleeding ) . Two cases of simple hyperplasia were reported ( one in each low-dose progestogen group ) . Beneficial effects on coronary heart disease risk factors , such as reductions in total cholesterol and low-density lipoprotein cholesterol and increases in high-density lipoprotein-2 cholesterol levels , were measured in all treatment groups . Lipoprotein ( a ) was reduced in all but the oral progestogen group . CONCLUSIONS Continuous and sequential transdermal estrogen/progestogen treatments with estradiol/NETA appear to be effective and safe alternatives to continuous transdermal estrogen and oral sequential progestogen for the treatment of menopausal symptoms . Continuous transdermal therapy with estradiol/NETA may be more acceptable for a majority of patients , i.e. , those who wish to avoid monthly bleeds , whereas the sequential regimen may be preferable when the clinician and /or patient believes monthly bleeding to be appropriate Objective The aim of this study is to investigate the effectiveness and safety of a Chinese herbal formula , Er-Xian decoction ( EXD ) , in the treatment of menopausal symptoms among Hong Kong perimenopausal women . Methods A r and omized , double-blind , controlled trial was conducted for 12 weeks among 108 Hong Kong perimenopausal women who reported Menopause Rating Scale ( MRS ) total scores of 28 or higher . Posttreatment follow-up was performed 3 months after the intervention . The primary outcome measure was the frequency and severity of hot flushes . The secondary outcome measures included the MRS , the Menopause-Specific Quality of Life question naire , and serum hormone levels . Results Among 108 participants , 101 participants finished the study . EXD significantly reduced the mean ( SD ) frequency of hot flushes from 5.8 ( 5.0 ) to 2.2 ( 3.0 ) in the treatment group and from 5.0 ( 3.8 ) to 2.4 ( 2.5 ) in the placebo group ( P = 0.04 ) . The mean ( SD ) hot flush score was also reduced from 19.6 ( 6.6 ) to 4.9 ( 7.8 ) in the treatment group and from 16.6 ( 5.4 ) to 7.0 ( 6.4 ) in the placebo group ( P = 0.02 ) . The superiority of EXD to placebo was also observed with greater improvement in the total scores for the MRS ( P = 0.03 ) and the Menopause-Specific Quality of Life question naire ( P < 0.01 ) . There were no differences in serum hormone levels between the EXD group and the placebo group . There were no serious adverse events , and the safety indices of whole blood counts , renal function , and liver function were within the normal range before and after treatment . Conclusions The Chinese herbal formula EXD is superior to placebo in reducing the frequency and severity of hot flushes and in improving menopausal symptoms in Hong Kong perimenopausal women . It is well tolerated , with no serious adverse events noted during the study period OBJECTIVE To assess the efficacy , tolerability , and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol ( E2 ) , compared with placebo , for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women . METHODS Women with moderate to severe vasomotor symptoms ( seven or more per day or 56 per week average ) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 ( n = 113 ) or 100 microg per day E2 ( n = 112 ) , or a placebo vaginal ring ( n = 108 ) . Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale . Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology . Participant satisfaction with the vaginal ring was evaluated via question naire . RESULTS Vasomotor symptoms significantly improved in both treatment groups , compared with placebo ( P < .05 ) . There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo . For women with vaginal atrophy at baseline ( n = 60 ) , the maturation index improved significantly in both treatment groups compared with placebo . Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups ( P < .05 ) compared with placebo . The vaginal rings were well tolerated . Most adverse events were mild or moderate and consistent with estrogen therapy . CONCLUSION A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms , compared with placebo . The E2 vaginal ring was well tolerated & NA ; Trigonella foenum‐graecum seed extract has demonstrated hormone modulatory activity , providing biological plausibility for relieving menopausal symptoms . The study aim ed to assess efficacy of a st and ardized T. foenum‐graecum de‐husked seed extract in reducing menopausal symptoms in healthy aging women . The study was a double‐blind , r and omized , placebo‐controlled trial that recruited 115 women aged 40 to 65 years of which 59 were allocated to active ( n = 54 completed ) and 56 to placebo ( n = 50 completed ) . Active treatment was T. foenum‐graecum de‐husked seed extract , 600 mg per day for 12 weeks . Outcome measures included Menopause‐Specific Quality of Life ( MENQOL ) question naire , frequency of hot flushes and night sweats and serum estradiol levels . There was a significant reduction in menopausal symptoms in the active group compared with placebo as assessed by total MENQOL score ( p < 0.001 ) ; reflected by significant improvements in the vasomotor ( p < 0.001 ) , psychosocial ( p < 0.001 ) , physical ( p < 0.001 ) and sexual symptoms ( p < 0.001 ) domains . Vasomotor outcomes correlated with hot flushes , the active group reporting significantly less daytime hot flushes and night sweats at 12 weeks ( p < 0.001 ) . The average estradiol levels were similar in both the active group and placebo group after treatment . This study demonstrated that this proprietary T. foenum‐graecum de‐husked seed extract may reduce menopausal symptoms in healthy women Objective : The study aims to evaluate the effectiveness and safety of Chinese herbal medicine granules Danzhi Qing’e formula ( DZQE ) , Erzhi formula ( EZ ) , and their combination ( Combined formula ) in the treatment of menopausal symptoms at different stages of menopause . Methods : Women between the ages of 40 to 60 years , who met menopausal symptoms diagnostic criteria and experienced hot flushes at least 14 times/week in the last 4 weeks , were recruited to participate in a stratified r and omized , double-blind , placebo-controlled clinical trial ( n = 389 ) . They received a treatment period of 8 weeks and were followed up for 4 weeks . Participants were categorized into two subgroups : 197 in the perimenopausal subgroup ( menstrual disorder to 1 y after amenorrhea ) and 192 in the early postmenopausal subgroup ( 1 - 5 y after amenorrhea ) . Participants were r and omly assigned to placebo or one of the three herbal formula treatments . The primary outcome instrument was the Menopause-Specific Quality of Life ( MENQOL ) question naire . Results : When analyzing the two subgroups together , DZQE markedly decreased the MENQOL total score at the end of 12th week with statistical significance ( P = 0.02 ) and improved vasomotor symptoms after 8 weeks treatment and 4 weeks follow-up ( P < 0.05 ) . What is more , the combined formula also greatly improved the participants ’ vasomotor symptoms compared with placebo after the 4 weeks follow-up . No statistically meaningful difference was observed in any other outcomes among the groups . The results of subgroup analysis showed that DZQE and Combined formula were more effective than placebo in improving MENQOL total score for perimenopausal women at the end of week 12 . For typical menopausal symptoms such as hot flushes and night sweats , DZQE displayed more favorable effects on early postmenopausal participants . Compared to placebo , the DZQE both showed statistically significant differences after 8 weeks treatment and 4 weeks follow-up . Although at the end of 12th week , DZQE also had better effects than placebo in the perimenopausal subgroup on vasomotor symptoms . Participants in the EZ group did not show a significant difference of any domains in MENQOL compared with participants in the placebo group . Conclusions : The DZQE formula improves the quality of life for menopausal women , especially for those with vasomotor symptoms during the whole menopausal period . The DZQE and EZ combination formula is effective only on perimenopausal symptoms OBJECTIVE To compare the efficacy and tolerability of three transdermal systems ( Estrapatch 40 , Estrapatch 60 and Oesclim 50 ) . METHODS Multicentre , r and omized , open , 3 parallel group study on 421 postmenopausal women presenting with at least 35 hot flushes in the week preceding inclusion and treated for six 28-day cycles with either Estrapatch 40 ( n = 141 ) or Estrapatch 60 ( n = 140 ) once a week or Oesclim 50 ( n = 140 ) twice a week , associated to oral NETA ( Millligynon 2x 0.6 mg tablets daily ) from day 15 to day 28 . Hot flushes , mastodynia , bleeding , local skin tolerability and adhesiveness were reported on daily cards . Endometrial thickness and estrogens were measured before and after treatment . RESULTS Efficacy was clearly established for the three devices as early as after one cycle of treatment , with success rates ( % of women with a decrease > or = 50 % of the number of hot flushes ) over 97 % from cycle 2 . The three treatments were equivalent on this criteria , except at cycle 1 for Estrapatch 40 which was not equivalent to both other treatments . Incidence and severity of mastodynia , bleeding pattern , endometrial thickness and specific estrogen-related adverse events reflected a significant higher estrogenic stimulation with Oesclim 50 . Adhesiveness was very satisfactory for the three systems . CONCLUSIONS Estrapatch 40 and 60 presents a better benefit/risk ratio compared to Oesclim 50 . Thus Estrapach 40 appears to be a good choice for a first-line estrogen replacement therapy with the possibility to increase the dose to Estrapatch 60 OBJECTIVES To examine the efficacy of a hop extract enriched in 8-prenylnaringenin ( 8-PN , the phytoestrogen in hops , Humulus lupulus L. ) on relief of menopausal discomforts . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled study over 12 weeks with 67 menopausal women , who were administered a hop extract st and ardized on 8-PN ( 100 or 250 microg ) . The responses were determined by means of a modified Kupperman index ( KI ) and a patients ' question naire . RESULTS All groups , including placebo , showed a significant reduction of the KI both after 6 weeks and after 12 weeks . The hop extract at 100 microg 8-PN was significantly superior to placebo after 6 weeks ( P=0.023 ) but not after 12 weeks ( P=0.086 ) . No dose-response relationship could be established , as the higher dose ( 250 microg ) was less active than the lower dose both after 6 weeks and after 12 weeks . Still , a trend for a more rapid decrease of KI was noticed for both active groups as compared to placebo . In particular , the decrease in hot flush score ( isolated from the KI ) was found significant for both treatment groups after 6 weeks ( P<0.01 ) with respect to placebo . Results of the patients ' question naire were consistent with those of the KI , with the most pronounced effects being observed for the 100-microg treatment . CONCLUSIONS Daily intake of a hop extract , st and ardized on 8-PN as a potent phytoestrogen , exerted favorable effects on vasomotor symptoms and other menopausal discomforts . Hop-derived prenylated flavonoids may provide an attractive addition to the alternative treatments available for relief of hot flushes and other menopausal discomforts Objective To investigate the effect of an oral soy isoflavone extract ( Phytosoya ) on hot flushes in menopausal women . Design The study was conducted on out patients according to a multicenter , r and omized , double-blind , placebo-controlled , parallel-group design . A total of 75 patients in natural or surgical menopause suffering from at least seven hot flushes per day were r and omized to receive during 4 months either soy isoflavone extract ( total of 70 mg genistin and daidzin per day ) or placebo . Results There is evidence to suggest that 16 weeks of treatment with soy extract can help reduce the mean number of hot flushes per 24 hours in menopausal women . Withdrawals during this trial made it difficult to obtain an unbiased estimate of the true treatment effect , but numerous sensitivity analyses lend support to the suggestion that taking soy extract can be beneficial in the treatment of hot flushes . In particular , women taking soy extract had a 38 % reduction in the mean number of hot flushes by week 4 and a 51 % reduction by week 8 . By the end of week 16 , patients taking soy extract had a 61 % reduction in their daily hot flushes versus a 21 % reduction obtained with the placebo . “ Responders ” ( defined as patients whose hot flushes were reduced by at least 50 % at the end of treatment period ) were 65.8 % in the soy extract group and 34.2 % in the placebo group ( p < 0.005 ) . ConclusionS oy isoflavone extract may help to reduce the frequency of hot flushes in climacteric women and provides an attractive addition to the choices available for relief of hot flushes INTRODUCTION Menopause is one of the most important crises in the life of women . The control of menopause symptoms is a main challenge in providing care to this population . So , the aim of present study was to investigate the effect of education through support -group on early symptoms of menopause . METHODS In this r and omized controlled clinical trial 124 postmenopausal women who had a health records in Valiasr participatory health center of Eslamshahr city were participated . These women were allocated by block r and omization method into support group ( 62 women ) and control group ( 62 women).Women in support group was assigned into 6 groups . Three 60-minutes educational sessions were conducted in 3 sequential weekly sessions . Early menopausal symptoms were measured before and 4 weeks after the intervention by using Greene scale ( score ranged from 0 to 63 ) . Data analysis was performed by ANCOVA statistical test . RESULTS There were no statistical differences between two groups in demographic characteristics and the total score of the Greene scale before intervention . The mean score of the Greene scale in support group was statistically less than control group 4 weeks after intervention . The number of hot flashes in the support group was significantly lower than control group , 4 weeks after intervention . CONCLUSION Education through support group was effective in reducing the early symptoms of menopause . Thus , this educational method can be used as an appropriate strategy for enhancing women ' health and their dealing with annoying symptoms of menopause Objectives : To evaluate the efficacy and safety of different doses of 17&bgr;‐estradiol for the treatment of vasomotor and vulvovaginal symptoms . Design : This was a r and omized , double‐blind , multicenter , parallel‐group study . One hundred forty‐five subjects , including naturally postmenopausal women aged 40‐60 ( who had not experienced menses for at least 12 months ) , women who had undergone hysterectomy , and women aged 25‐60 who had undergone bilateral oophorectomy with or without hysterectomy were studied . Either placebo or 17&bgr;‐estradiol ( 1 mg or 0.5 mg ) was given orally every day for 12 weeks , and vasomotor symptoms and vaginal epithelial cytology were evaluated . Results : There were significant differences between placebo and the active treatments in the percentage change from baseline in the number of hot flushes ( all hot flushes , 1 mg vs. placebo , p < 0.001 ; 0.5 mg vs. placebo , p = 0.007 ) , with a more substantial proportion of subjects responding in the 1‐mg group ( mean change in mean number of hot flushes of 83.2 % ) . Both doses were also more effective than placebo in increasing the proportion of mature vaginal cells ( end‐of‐treatment mean values of 0 % , 78.5 % , and 21.5 % for parabasal , intermediate , and superficial cells , respectively , in the 1‐mg group ; mean values of 0.3 % , 80.8 % , and 18.9 % in the 0.5‐mg group ; and mean values of 15.2 % , 74.7 % , and 10.2 % in the placebo group ) . The proportion of subjects reporting no vaginal dryness was greatest in the 1‐mg group ( mean percentage of days without dryness of 86.1 % at weeks 9‐12 ) . Conclusions : For the relief of vasomotor and vulvovaginal symptoms , 17&bgr;‐estradiol 1 mg is effective and has an excellent safety profile . ( Menopause 2000;7:310‐317 . © 2000 , The North American Menopause Society . OBJECTIVE : To investigate whether L-isoleucine was effective in the treatment of hot flushes and whether L-isoleucine , L-valine , or the combination of both amino acids reduced fasting serum homocysteine . METHODS : After a 1-week baseline period , 100 postmenopausal women experiencing at least five moderate-severe hot flushes per day were r and omized with equal probability to one of four groups ( phase 1/phase 2 ) : placebo/L-valine , placebo/L-valine and L-isoleucine , L-isoleucine/L-valine , and L-isoleucine/L-valine and L-isoleucine . Phase 1 was 12 weeks long , and phase 2 was 10 weeks long . Patients took five capsules by mouth , twice a day throughout the study , with each capsule containing 500 mg of compound . Data were obtained from daily hot flush diaries , fasting blood work , and several question naires . The primary outcome variable was the percent change in hot flush composite score from baseline to week 12 . RESULTS : In phase 1 of the study , there were no significant differences between the L-isoleucine and placebo groups for any of the outcome measures . At week 12 , there was a mean 13.9 % decrease in hot flush composite score compared with baseline in the L-isoleucine group and a mean 25 % decrease in the placebo group ( P=.28 ) . In phase 2 of the study , there was no significant change in fasting serum homocysteine levels associated with any of the amino acid therapies . CONCLUSION : L-isoleucine therapy appears to be ineffective in the treatment of hot flushes in postmenopausal women . L-isoleucine and L-valine , either alone or in combination , appear to have no effect on fasting serum homocysteine levels . CLINCIAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00081952 Level of Evidence : OBJECTIVE : To investigate the safety and efficacy of a transdermal estradiol ( E2 ) spray in women with postmenopausal vasomotor symptoms . METHOD : A r and omized , double-blind , placebo-controlled , multicenter , parallel-group clinical trial was conducted . Postmenopausal women ( N=454 ) with at least eight moderate-to-severe hot flushes per day applied daily , one , two , or three E2 ( 90 microliter spray contains 1.53 mg E2 ) or matching placebo sprays . The primary efficacy endpoints were mean change from baseline in frequency and severity of moderate-to-severe hot flushes at weeks 4 and 12 . RESULTS : All three E2 groups showed a significant decrease in hot flushes at weeks 4 and 12 compared with their placebo groups ( P<.010 ) . The mean change in frequency at week 12 was eight fewer flushes per day for women in the E2 groups and between four and six fewer flushes for women in the placebo groups . Women in the three- and two-E2 spray groups demonstrated significant ( P<.050 ) reductions in severity score at weeks 4 and 12 ; women in the one-spray group showed significant reductions at week 5 . At week 12 , the majority ( 74–85 % ) of women on E2 showed at least a 50 % hot flush frequency reduction as compared with 46 % in the placebo group . The systemic E2 delivery rates at week 12 were approximately 0.021 mg/d , 0.029 mg/d , and 0.040 mg/d for the one- , two- , and three-spray doses , respectively . Common adverse events were similar to those previously reported with other transdermal products . Treatment-related application site reaction rate was similar to placebo ( 1.3 % compared with 1.8 % ) . CONCLUSION : The three dose levels of E2 spray achieved efficacy at 0.021–0.040 mg/d delivery rates . The spray is a well-tolerated , new , convenient method of delivering low-dose E2 transdermally . Clinical Trial Registration : Clinical Trials.gov , www . clinical trials.gov , NCT00122200 LEVEL OF EVIDENCE : Objective To determine the efficacy and tolerability of two strengths of percutaneous 17&bgr;-estradiol in a hydroalcoholic gel and placebo in controlling vasomotor symptoms of menopause . Design A total of 221 postmenopausal women were assigned r and omly to treatment with percutaneous 17&bgr;-estradiol gel 1.25 g ( containing 0.75 mg of estradiol ) or 2.5 g ( containing 1.5 mg of estradiol ) or placebo gel applied once daily for 12 weeks . The primary efficacy variable was the mean change from baseline in the frequency of moderate/severe hot flushes . In addition , the mean changes from baseline in the frequency and severity of all hot flushes were assessed . Safety and tolerability were evaluated from endometrial biopsy , adverse events , and laboratory tests . Results A significant reduction ( P < 0.05 ) in the mean frequency of moderate-to-severe hot flushes and mean frequency and severity of all hot flushes was observed with both 17&bgr;-estradiol gel groups compared with placebo . The mean number of moderate-to-severe hot flushes at the end of the study with 17&bgr;-estradiol gel 2.5 g , 17&bgr;-estradiol gel 1.25 g , and placebo gel was 2.0 , 2.8 and 5.2 , respectively . The overall incidence of adverse events was not significantly different among groups , though a higher incidence of estrogen-related adverse events was reported with the 17&bgr;-estradiol gel 2.5-g dose . Conclusions 17&bgr;-estradiol gel was effective and well tolerated for alleviating moderate-to-severe hot flushes in postmenopausal women . Therapy may be initiated with the 1.25-g dose with an increase to the 2.5-g dose if needed Objective This report describes the Menopausal Strategies : Finding Lasting Answers to Symptoms and Health network and method ological issues addressed in design ing and implementing vasomotor symptom trials . Methods Established in response to a National Institutes of Health request for applications , the network was charged with conducting rapid throughput r and omized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms . Included are descriptions of and rationale for criteria used for interventions and study selection , common eligibility and exclusion criteria , common primary and secondary outcome measures , consideration of placebo response , establishment of a biorepository , trial duration , screening and recruitment , statistical methods , and quality control . All trial design s are presented , including the following : ( 1 ) a r and omized , double-blind , placebo-controlled clinical trial design ed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity ; ( 2 ) a two-by-three factorial design trial to test three different interventions ( yoga , exercise , and & ohgr;-3 supplementation ) for the improvement of vasomotor symptom frequency and bother ; and ( 3 ) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency . The network ’s structure and governance are also discussed . Conclusions The methods used in and the lessons learned from the Menopausal Strategies : Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other research ers Objective : To compare effects of 52 weeks ' treatment with either raloxifene 60 mg/day alone ( RLX ) or in combination with 17&bgr;-estradiol 1 mg/day ( RLX + E ) on vasomotor symptoms ( n = 83 ) and endometrial safety ( n = 123 ) in postmenopausal women who transitioned from estrogen-progestin therapy . Design : In this r and omized , double-blind clinical trial , the frequency of vasomotor symptoms , hot flashes , and night sweats was assessed for up to 52 weeks . Endometrial thickness was assessed by transvaginal ultrasonography at baseline and at 12 and 52 weeks . An exit endometrial biopsy was performed at study completion or early termination . Results : The frequency of vasomotor symptoms , hot flashes , and night sweats was unchanged from baseline with RLX but was significantly reduced in women treated with RLX + E , from baseline ( all P < 0.001 ) and the RLX group at 6 , 12 , 24 , 36 , and 52 weeks ( all P < 0.01 ) . Women in the RLX + E group had significantly increased endometrial thickness ( 0.74 ± 0.28 mm , mean ± SEM ) at 52 weeks , from baseline and RLX ( P < 0.05 ) , with no statistically significant changes in women treated with RLX . Two women , both in the RLX + E group , had endometrial hyperplasia ( one with atypia ) on the exit biopsy . Conclusions : In women transitioning from estrogen-progestin therapy , occurrence of vasomotor symptoms was unchanged from baseline with RLX treatment , but these symptoms were significantly reduced with combined RLX + E therapy . Signs of endometrial stimulation were observed in the RLX + E group . Further studies using different estrogen doses and preparations are needed before concomitant use of raloxifene with systemic estrogens can be recommended Objective This study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms . Methods Late perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms ( VMS ) participated in a r and omized controlled trial conducted in three sites : 106 women r and omized to exercise and 142 women r and omized to usual activity . The exercise intervention consisted of individual facility-based aerobic exercise training three times per week for 12 weeks . VMS frequency and bother were recorded on daily diaries at baseline and on weeks 6 and 12 . Intent-to-treat analyses compared between-group differences in changes in VMS frequency and bother , sleep symptoms ( Insomnia Severity Index and Pittsburgh Sleep Quality Index ) , and mood ( Patient Health Question naire-8 and Generalized Anxiety Disorder-7 question naire ) . Results At the end of week 12 , changes in VMS frequency in the exercise group ( mean change , −2.4 VMS/d ; 95 % CI , −3.0 to −1.7 ) and VMS bother ( mean change on a four-point scale , −0.5 ; 95 % CI , −0.6 to −0.4 ) were not significantly different from those in the control group ( −2.6 VMS/d ; 95 % CI , −3.2 to −2.0 ; P = 0.43 ; −0.5 points ; 95 % CI , −0.6 to −0.4 ; P = 0.75 ) . The exercise group reported greater improvement in insomnia symptoms ( P = 0.03 ) , subjective sleep quality ( P = 0.01 ) , and depressive symptoms ( P = 0.04 ) , but differences were small and not statistically significant when P values were adjusted for multiple comparisons . Results were similar when considering treatment-adherent women only . Conclusions These findings provide strong evidence that 12 weeks of moderate-intensity aerobic exercise do not alleviate VMS but may result in small improvements in sleep quality , insomnia , and depression in midlife sedentary women Extracts from Cimicifuga racemosa ( CR , synonym Actaea racemosa ) have shown efficacy in trials in women with menopausal symptoms . Yet , dose dependency remains unclear . Therefore , 180 female out patients with climacteric complaints were treated for 12 weeks in a r and omized , double-blind , placebo-controlled , 3-armed trial ( CR extract Ze 450 in 6.5 mg or 13.0 mg , or placebo ) . Primary outcome was the difference in menopausal symptoms ( vasomotor , psychological , and somatic ) , assessed by the Kupperman Menopausal Index between baseline and week 12 . Secondary efficacy variables were patients ' self- assessment s of general quality of life ( QoL ) , responder rates , and safety . Compared to placebo , patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint ( mean absolute differences 17.0 ( 95 % CI 14.65–19.35 ) score points , P < 0.0001 for 13.0 mg ; mean absolute differences 8.47 ( 95 % CI 5.55–11.39 ) score points , P = 0.0003 for 6.5 mg ) . QoL and responder rates corresponded with the main endpoint . Changes in menopausal symptoms and QoL were inversely correlated . Reported adverse events and clinical laboratory testing did not raise safety concerns . The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women This clinical research study was design ed to evaluate the efficacy of a new herbal product , EstroG-100 , containing a mixture of st and ardized extracts of Cynanchum wilfordii , Phlomis umbrosa and Angelica gigas , on menopausal symptoms . This r and omized double-blind , placebo-controlled trial was performed for 12 weeks with 64 pre- , peri- and postmenopausal White Hispanic , White non-Hispanic and African American women who were r and omly allocated to either the EstroG-100 group ( n = 31 ) or the placebo group ( n = 33 ) . Primary end-points were the mean change in scores of the Kupperman menopause index ( KMI ) that evaluates 11 symptoms , and the mean change in scores of vaginal dryness . The mean KMI score was significantly reduced in the EstroG-100 group from 29.5 ± 7.4 at baseline to 11.3 ± 5.8 ( p < 0.01 ) compared with change of the placebo group ( 29.2 ± 6.6 at baseline vs 23.7 ± 7.7 at week 12 ) . The constituting symptoms of vasomotor , paresthesia , insomnia , nervousness , melancholia , vertigo , fatigue and rheumatic pain were significantly improved in the EstroG-100 group in comparison with the placebo group ( p < 0.05 ) . Statistically significant improvement in vaginal dryness in the EstroG-100 group was also observed compared with that of the placebo group ( p < 0.05 ) . In conclusion , EstroG-100 significantly improved the menopausal symptoms of pre- , peri- and post-menopausal women without weight gain or any serious side effects ABSTRACT Valerian is one of the most widely used herbal supplements and a phytoestrogenic herb . The aim of this study was to determine the effect of Valerian on the severity and frequency of hot flashes . This triple-blind , r and omized , controlled clinical trial was conducted during a three-month period in Hamadan , Iran , in 60 postmenopausal women aged 45–55 years . Participants were r and omly assigned to one of two groups– either placebo or Valerian . An oral Valerian 530 mg capsule was given twice per day for two months . An oral placebo 530 mg capsule ( starch ) was similarly administered . The severity and frequency of hot flashes were determined by the Kupperman index , before the intervention , one month after , and two months after initiation of the intervention . The severity of hot flashes in the Valerian group was significantly lower than that in the placebo group at one ( p = .048 ) and two months ( p = .020 ) after initiation of the intervention . Compared with the placebo group , the mean frequency of hot flashes was significantly reduced two months after initiating the use of Valerian ( p = .033 ) . Health-care providers should consider Valerian to be effective for menopausal women with hot flashes Psychological and behavioural interventions may be effective in reducing menopause-related symptoms . This r and omized controlled trial aim ed to evaluate the effectiveness of Mindfulness-based Stress Reduction ( MBSR ) in reducing menopause-related symptoms by comparing with an active control group , the menopause education control ( MEC ) . Symptomatic peri-menopausal and post-menopausal women with mild to moderate symptoms were recruited . The primary outcome was overall menopausal symptoms measured by modified Greene Climacteric Scale ( GCS ) . Secondary outcomes include subscales of the GCS perceived stress , mindfulness and health related Quality of Life . All outcome measures were collected at baseline , 2 months ( immediately post intervention ) , 5 and 8 months ( 3 and 6 months post intervention respectively ) . Both MBSR ( n = 98 ) and MEC ( n = 99 ) groups reported a reduction in total GCS score at 8 months . Between group analysis show significant symptom score reduction in MBSR group on Anxiety and Depression subscales of GCS . No differences were found between groups on other GCS subscales and majority of the secondary outcome measures . The findings show that menopausal symptoms in both MBSR and MEC significantly reduced over the study period . MBSR show a greater reduction of psychological symptoms of depression and anxiety above active controls but do not reduce other somatic , urogenital and vasomotor symptoms Objective The aim of this study was to compare oral micronized progesterone ( progesterone ) with placebo as therapy for postmenopausal hot flushes and night sweats ( vasomotor symptoms [ VMS ] ) . Methods Healthy volunteer community women 1 to 10 years since final menstruation were recruited for a r and omized double-blind placebo-controlled trial of progesterone ( 300 mg daily at bedtime ) between 2003 and 2009 and were screened for clinical , physical , or laboratory evidence of cardiovascular risks ( nonsmoking , moderate body mass index [ < 35 kg/m2 ] , normal lipids , electrocardiogram , nondiabetic ) . Women recorded daily frequency and severity ( 1 - 4 ) of VMS in the Daily Menopause Diary during run-in ( 4 wk ) and intervention ( 12 wk ) . Average daily VMS score ( day frequency × day severity + night frequency × night severity ) during final 28 therapy days was the primary outcome , analyzed by therapy , with run-in score as covariate . Results R and omized participants were 133 healthy community women with VMS , ages 44 to 62 years , with a mean ( SD ) VMS score of 17.0 ( 10.4 ) at run-in ( VMS frequency 6.8 [ 3.2 ] episodes/d ) . Women were r and omized to progesterone ( n = 75 ) or placebo ( n = 58 ) ; analysis included all with VMS data at run-in and on therapy ( n = 68 and 46 , respectively ) . The VMS scores of women taking progesterone were better than placebo ( mean adjusted difference , −4.3 ( 95 % CI , −6.6 to −1.9 ) , with mean reductions of 10.0 ( 95 % CI , −12.0 to −8.1 ) and 4.4 ( 95 % CI , −6.6 to −2.2 ) in the progesterone and placebo arms , respectively . Discontinuation with adverse events was 9 % ( progesterone , 8 ; placebo , 4 ) , with no serious cases . Conclusions Oral micronized progesterone is effective for treatment of hot flushes and night sweats in healthy women early in postmenopause Background This study aims to evaluate the efficacy of Black cohosh ( Cimicifuga racemosa L. ) in treating early menopausal symptoms . Methods This r and omized , double-blind , placebo-controlled clinical trial was conducted on 84 early post-menopausal participants with Greene climacteric scale ( GCS ) scores of 15 to 42 , who were referred to two public health care centers in Tehran , Iran , in 2011–2012 . The participants were r and omly allocated into treatment ( 6.5 mg of dried extract of Black cohosh roots daily ) and control ( placebo ) groups with a ratio of 1:1 . The participants took one tablet per day for 8 weeks . The GCS scores were recorded at baseline , and after 4 and 8 weeks of treatment . Data analysis was carried out using a general linear model with repeated measures with SPSS software . The level of significance was set at P < 0.05 . Results There was no loss to follow-up during the 8 weeks of treatment . The GCS total score ( primary outcome ) in the treatment group was significantly lower than that in the control group at both week 4 [ adjusted mean difference : -7.8 ( 95 % confidence interval : -11.1 to -4.4 ) ] and week 8 [ -12.9 ( -16.2 to -9.3 ) ] . The treatment group showed significantly more improvement than the control group in all GCS subscale scores ( vasomotor , psychiatric , physical , and sexual symptoms ; secondary outcomes ) . The differences between the treatment and control groups at week 8 were significantly higher ( P < 0.001 ) than those at week 4 in terms of the total scores and the vasomotor and psychiatric subscale scores . No side effects were reported . Conclusions Black cohosh reduced the GCS total score and all GCS subscale scores ( vasomotor , psychiatric , physical , and sexual symptoms ) during 4 and 8 weeks of treatment . Clinical trial registration This study was approved ( Code 9061 ) by the Ethics Committee of Tabriz University of Medical Sciences and registered at the Iranian Registry of Clinical Trials withI RCT 201107186709N4 on 15 January 2012 Objective : Hot flashes are a significant problem in women going through the menopausal transition that can substantially affect quality of life . The world of estrogen therapy has been thrown into turmoil with the recent results of the Women 's Health Initiative trial report . Pursuant to a growing interest in the use of alternative therapies to alleviate menopausal symptoms and a few pilot trials that suggested that acupuncture could modestly alleviate hot flashes , a prospect i ve , r and omized , single-blind , sham-controlled clinical trial was conducted in women experiencing hot flashes . Design : Participants , after being r and omized to medical versus sham acupuncture , received biweekly treatments for 5 weeks after a baseline assessment week . They were then followed for an additional 7 weeks . Participants completed daily hot flash question naires , which formed the basis for analysis . Results : A total of 103 participants were r and omized to medical or sham acupuncture . At week 6 the percentage of residual hot flashes was 60 % in the medical acupuncture group and 62 % in the sham acupuncture group . At week 12 , the percentage of residual hot flashes was 73 % in the medical acupuncture group and 55 % in the sham acupuncture group . Participants reported no adverse effects related to the treatments . Conclusions : The results of this study suggest that the used medical acupuncture was not any more effective for reducing hot flashes than was the chosen sham acupuncture Background The fact that hormone replacement therapy has been cl aim ed to increase the risk of breast cancer has made it relevant to search for new non-hormonal treatments of menopausal symptoms . Objectives This study aim ed to evaluate whether Femal , a herbal remedy made from pollen extracts , alleviates the symptoms of the menopause , especially hot flushes . Design A r and omized , double-blind , placebo-controlled , parallel trial of 64 menopausal women , of whom 54 completed the trial . After an initial run-in phase of 1 month , the women were r and omly given either two Femal tablets each morning , or two identical placebo tablets , for 3 months of treatment . On inclusion , and then at 4-week intervals , the patients were asked to evaluate 16 symptoms of the menopause using Menopause Rating Scales ( MRS ) . In addition , every day throughout the study , certain menopausal symptoms were recorded in a diary . Results The two treatment groups were identical regarding demographic data and the initial symptom scores . In the active-treatment group , 65 % responded with a reduction in hot flushes compared with 38 % in the placebo group ( p < 0.006 ) and , in this group , the number of hot flushes registered in diaries declined after 3 months by 27 % as compared to the placebo group ( p < 0.026 ) . MRS evaluation of hot flushes yielded similar results ( p < 0.031 ) . There were 23 % and 22 % decreases in hot flushes after 2 and 3 months of treatment , respectively , and after both intervals of time the inter-group comparisons were significantly affected . An overall evaluation of the trend in 15 other ‘ quality -of-life ’ parameters showed likewise in favor of the pollen extract ( p < 0.031 ) . Conclusion The pollen extract Femal significantly reduces hot flushes and certain other menopausal symptoms when compared to placebo This multicenter , r and omized , controlled clinical study was design ed to address the effectiveness of combined traditional-Chinese-medicine- ( TCM- ) based psychotherapy and Chinese herbal medicine ( CHM ) in the treatment of menopausal syndrome . Altogether 424 eligible women diagnosed as menopausal syndrome and categorized as Kidney-Yin/Kidney-Yang deficiency pattern in TCM were r and omly assigned into 4 groups and accepted TCM-based psychotherapy ( PSY ) , CHM , PSY + CHM , or placebo therapies , respectively , for 12 weeks , and another 12 weeks were taken as the followup . Kupperman Index ( KI ) and the Menopause-Specific Quality of Life ( MENQOL ) with its four subscales ( vasomotor , physical , psychosocial , and sexual ) were employed for efficacy assessment . Results showed that 400 participants completed 12-week treatment , of which 380 finished the record of KI and MENQOF at week 24 . The average adjusted number of KI score decreased between baseline and 12 weeks in all groups . Statistically significant differences were detected in the average adjusted change between the PSY + CHM group and placebo at overall time points ( P < 0.05 ) . No severe adverse events occurred in each group and no significant differences were indicated between any of the three groups and placebo in adverse event proportion . We concluded that TCM psychotherapy combined with CHM has a favorable outcome in treating menopausal syndrome PURPOSE Vasomotor symptoms , such as hot flashes and night sweats , in breast cancer survivors are often worsened by chemotherapy and tamoxifen , and /or the discontinuation of hormone replacement therapy at diagnosis . This study evaluated the acceptability and effectiveness of a soy beverage containing phytoestrogens as a treatment for hot flashes in postmenopausal women with breast cancer . METHODS A r and omized , placebo-controlled , double-blind clinical trial was conducted in postmenopausal women with moderate hot flashes who were previously treated for early-stage breast cancer . Women were stratified for tamoxifen use and r and omized to a soy beverage ( n = 59 ) containing 90 mg of isoflavones or to a placebo rice beverage ( n = 64 ) . Women recorded the number and severity of hot flashes daily with a daily menopause diary for 4 weeks at baseline and for 12 weeks while consuming 500 mL of a soy or placebo beverage . RESULTS There were no significant differences between the soy and placebo groups in the number of hot flashes or hot flash scores . However , presumably because of a strong placebo effect , both groups had significant reductions in hot flashes . Mild gastrointestinal side effects were experienced by both groups but occurred with greater frequency and severity with soy . The mean serum genistein concentration at 6 weeks was significantly higher in women who consumed soy ( 0.61 + /- 0.43 micromol/L ) compared with placebo ( 0.43 + /- 0.37 micromol/L ) ( P = .02 ) . Overall acceptability and compliance were high and similar in both groups . CONCLUSION The soy beverage did not alleviate hot flashes in women with breast cancer any more than did a placebo . Future research into other compounds is recommended to identify safe and effective therapies for hot flashes in breast cancer survivors Objective : To determine the efficacy of three doses of a new , oral formulation of estradiol acetate ( EA ) for alleviation of vasomotor and urogenital symptoms in postmenopausal women . Design : Two separate 12-week studies were undertaken in postmenopausal women with moderate to severe vasomotor symptoms . In the first study , women were r and omly assigned to EA 0.9 mg/day , EA 1.8 mg/day , or placebo ( study 1 ; N = 293 ) , and in the second study to oral EA 0.45 mg/day or placebo ( study 2 ; N = 259 ) . Women recorded the frequency and severity of vasomotor symptoms daily and urogenital symptoms weekly on diary cards . Investigators assessed signs of vaginal atrophy . Results : Frequency of moderate to severe vasomotor symptoms decreased significantly versus placebo , starting at week 2 in the EA 1.8-mg group ( P = 0.005 ) , week 3 in the EA 0.9-mg group ( P = 0.003 ) , and week 6 in the EA 0.45-mg group ( P < 0.05 ) . At week 12 , mean percent reduction from baseline in vasomotor-symptom frequency was 91 % , 78 % , and 61 % , respectively . Vasomotor-symptom severity decreased significantly versus placebo , starting at weeks 2 and 3 with EA 1.8 mg and 0.9 mg , respectively , and at week 5 with EA 0.45 mg . Vaginal pH and maturation index improved significantly in all EA groups versus placebo , and some signs and symptoms of vaginal atrophy improved at the EA 0.9- and 1.8-mg doses . Side effects were mild to moderate and consistent with estrogen therapy . Conclusions : Oral EA at all doses was well tolerated and significantly reduced the frequency and severity of postmenopause symptoms versus placebo We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression . Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes , mood status , and health-related quality of life . We used a r and omized , double-blind , placebo-controlled , crossover study using 6 weeks of sertraline ( 50 mg each morning ) versus placebo . Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes . Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity , from which hot flash scores ( frequency x severity ) were calculated . The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy -- Breast ( FACT-B ) ( at baseline , 6 weeks , and 12 weeks ) were used to assess mood and quality of life . Sixty-two women were accrued . Forty-seven women ( median age 53.9 years , range 36.6 - 77.1 years ; 89 % postmenopausal ; 85.5 % Caucasian ) completed the first 6 weeks and 39 completed 12 weeks . The baseline daily hot flash frequency and score were 5.8 ( st and ard deviation 4.1 ) and 11.5 ( 14.0 ) , respectively . At the end of the first 6 weeks , hot flash frequency decreased by 50 % in 36 % of those taking sertraline compared to 27 % taking placebo . In the crossover analysis , sertraline was significantly more effective than placebo : women crossing from placebo to sertraline had a decrease ( -0.9 and -1.7 ) in hot flash frequency and score , whereas those crossing from sertraline to placebo had an increase ( 1.5 and 3.4 ) in hot flash frequency and score ( p = 0.03 and 0.03 ) . Forty-eight percent preferred the sertraline period , 11 % preferred the placebo period , and 41 % had no preference ( p = 0.006 ) . Measures of depression and quality of life were within normal range and did not change significantly within treatment groups . Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo . Further study of sertraline for the management of hot flashes is warranted OBJECTIVE : To evaluate two doses of oral synthetic conjugated estrogens-B tablets compared with placebo on the frequency of awakenings result ing from nocturnal vasomotor symptoms in postmenopausal women over a 12-week treatment period . METHODS : A double-blind , r and omized , placebo-controlled multicenter study enrolled a total of 157 women who were experiencing daytime vasomotor symptoms and a minimum of at least three nocturnal awakenings per night as a result of hot flushes . Participants were evenly r and omized to one of three treatment groups ( 0.3 mg , 0.625 mg , or matching placebo ) and treated for up to 12 weeks . Subjective sleep quality also was assessed . RESULTS : Significantly greater reductions from baseline in the weekly mean frequency of awakenings result ing from hot flushes occurred for participants r and omized to either synthetic conjugated estrogens-B dose relative to placebo ( mean reductions , 3.55 , P=.004 , and 4.65 , P<.001 for 0.3 mg and 0.625 mg , respectively ) . In addition , a significantly greater proportion of participants at either estrogen dose had complete elimination of nocturnal awakenings ( 36.5 % for 0.3 mg , 34 % for 0.625 mg compared with 9.8 % for placebo ; P⩽.002 ) with a general finding of improved sleep based on actigraphy data . No differences were observed in measures of sleep quality or daytime sleepiness . CONCLUSION : In this symptomatic postmenopausal population of women experiencing sleep disruption result ing from nocturnal vasomotor symptoms , a daily dose of synthetic conjugated estrogens-B as low as 0.3 mg appears to be effective in treating nocturnal hot flushes that lead to unwanted awakenings . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00592839 . LEVEL OF EVIDENCE : PURPOSE Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment . Black cohosh has been used to treat hot flashes , but definitive clinical data about efficacy have been equivocal . METHODS A double-blind , r and omized , cross-over clinical trial with two 4-week periods , was used to study the efficacy of black cohosh ( 1 capsule , Cimicifuga racemosa 20 mg BID ) for the treatment of hot flashes in women . Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods . Hot flash scores were measured by assigning points ( 1 to 4 for mild to very severe ) to each hot flash based on severity and then adding the points for a given time period . RESULTS Between October 31 , 2003 , to March 4 , 2004 , 132 patients were r and omly assigned . Toxicity was minimal and not different by treatment group . Patients receiving black cohosh reported a mean decrease in hot flash score of 20 % ( comparing the fourth treatment week to the baseline week ) compared with a 27 % decrease for patients on placebo ( P = .53 ) . Mean hot flash frequency was reduced 17 % on black cohosh and 26 % on placebo ( P = .36 ) . Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period , if any , the patient preferred . Thirty-four percent of patients preferred the black cohosh treatment , 38 % preferred the placebo , and 28 % did not prefer either treatment . CONCLUSION This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo BACKGROUND Classical hormone replacement therapy for hot flashes is contraindicated in breast cancer especially in endocrine responsive disease . PATIENTS AND METHODS In a double-blind , r and omized phase III study , breast cancer patients suffering from hot flashes at least twice a day , who were not taking any medication against hypertension and depression received either clonidine 0.075 mg twice a day or venlafaxine 37.5 mg twice a day for 4 weeks . The primary end point was defined as the frequency of hot flashes after 4 weeks of treatment . A self-reported 1-week hot flash and other symptom question naire were kept before the start of treatment until the end of treatment course . RESULTS From April 2002 to October 2004 , 80 patients were recruited of whom 64 were assessable for efficacy analyses . Thirty-three received clonidine and 31 venlafaxine , nine patients stopped early because of side-effects and seven withdrew consent . At the end of treatment week 4 , the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes per day for those receiving clonidine ( P = 0.025 ) . CONCLUSION Venlafaxine is significantly more effective in reducing the frequency of hot flashes in breast cancer patients than clonidine BACKGROUND To evaluate the differences between the immediate and tapered cessation protocol s of hormone therapy in terms of recurrence of menopausal symptoms . MATERIAL S AND METHODS In this prospect i ve , r and omized clinical study 70 consecutive patients in whom hormone therapy was no longer preferred were recruited from the menopause clinic of a university hospital and rank r and omized into two groups . In group 1 ( n=35 ) hormone therapy was immediately discontinued and in group 2 ( n=35 ) the medication was tapered . Every patient was question ed about vasomotor symptoms before the initiation of hormone therapy at the first visit , and then revisited at the end of 2 and 4 weeks . RESULTS We did not find any statistically significant difference between two protocol s in terms of symptom severity and frequency at the end of 2 and 4 weeks of discontinuation . Although statistically insignificant , the symptoms tended to recur in fewer patients and in a less severe form in both groups when compared with their pretreatment status . CONCLUSIONS Tapering or immediate discontinuing of hormone therapy did not affect the recurrence rate and severity of menopausal symptoms at the end of 4 weeks Purpose To compare symptomatic response in Indian women using different estrogen preparations for treatment of menopausal symptoms . Methodology A r and omized , single blind , four arm , parallel assignment study was conducted in VMMC and SJH , New Delhi , India . 200 Indian menopausal women were recruited and assigned into four treatment groups viz . , estradiol valerate ( E2V ) , conjugated equine estrogen ( CEE ) , isoflavones and Placebo group . The statistical significance of categorical variables was determined by Chi-square , Fisher ’s exact test . In case of quantitative variable parametric test Student ’s t test was used . In case of quantitative variables where data are not normally distributed , Kruskal – wallis test and Wilcoxon Mann – Whitney test were used . Symptomatic response in vasomotor/vaginal symptoms was assessed in all groups . Results Both E2V and CEE groups were effective in reducing severity and frequency of hot flashes . 91.9 % decrease was observed in mean hot flash score in the E2V group after 24 weeks of treatment , 89.2 % in the CEE group , 60.42 % decrease in the isoflavones group . While placebo led to 47.9 % decrease in mean hot flash score . After 24 weeks of therapy there was significant increase in vaginal health index in the E2V and CEE and the isoflavones group . No serious side effect was reported in any of the groups . Conclusion Low doses of both CEE and E2V were equally effective for management of vasomotor/vaginal symptoms when administered over 24 weeks . However , it seems more reasonable to replenish with less costly and bio-identical hormone , i.e. micronized estradiol valerate which is equally effective . Trial registryThe trial was registered under Clinical trial registry of India prospect ively ( number : CTRI/2012/04/002566 ) OBJECTIVE : To investigate the efficacy of the fixed combination of black cohosh ( Cimicifuga racemosa ) and St. John ’s wort ( Hypericum perforatum ) extracts in women with climacteric complaints with a pronounced psychological component . METHODS : In this double-blind r and omized placebo-control study , 301 women experiencing climacteric complaints with psychological symptoms were treated with ethanolic St. John ’s wort extract and isopropanolic black cohosh extract or a matched placebo for 16 weeks . Climacteric complaints were evaluated by means of the Menopause Rating Scale mean score , and psychological complaints were evaluated using the Hamilton Depression Rating Scale sum score . RESULTS : The mean ( ± st and ard deviation ) Menopause Rating Scale score decreased 50 % ( 0.46 ± 0.13 to 0.23 ± 0.13 ) in the treatment group and 19.6 % ( 0.46 ± 0.14 to 0.37 ± 0.15 ) in the placebo group . The Hamilton Depression Rating Scale total score decreased 41.8 % in the treatment group ( 18.9 ± 2.2 to 11.0 ± 3.8 points ) , and 12.7 % in the placebo group ( 18.9 ± 2.1 to 16.5 ± 4.3 ) . The treatment was significantly ( P < .001 ) superior to placebo in both measures . There were no relevant group differences regarding adverse events , laboratory values , or tolerability . CONCLUSION : This fixed combination of black cohosh and St. John ’s wort is superior to placebo in alleviating climacteric complaints , including the related psychological component . LEVEL OF EVIDENCE : OBJECTIVES To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch ( Fem7 , Merck KGaA , Germany ) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo . DESIGN A multicentre , r and omized , double-blind study with an initial screening phase ( phase I ) , a 3-month double-blind placebo-controlled phase ( phase II ) and a 3-month open follow-up phase ( phase III ) . METHODS 186 patients were r and omized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up ( total duration ; 6 months ) . The changes in Kupperman Index ( primary efficacy variable ) , hot flushes and urogenital symptom score were studied from baseline to the end of the study . In addition , skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy . RESULTS A reduction in Kupperman Index was observed in both groups , and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo ( last value vs. baseline P = 0.0006 ) . From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group . The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase ( mean weekly hot flush reduction at the end of the placebo-controlled treatment phase : -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo , P = 0.0025 ) . The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1 - 3 and 4 - 7 . Subjective acceptance of the 7-day-Estradiol patch was good and 72.4 % of patients who took active medication throughout the study were willing to consider continuing its use . CONCLUSIONS The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women , with a rapid onset of action and 7-day duration of therapeutic effect . Although a placebo effect was observed , the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period OBJECTIVE The objective of this clinical trial was to examine the efficacy of a supplement containing natural S-(-)equol , a daidzein metabolite , in reducing menopausal symptoms . METHODS In this multicenter , double-blind placebo-controlled trial , 160 equol nonproducing , postmenopausal Japanese women who experienced at least 1 hot flush/day were r and omly assigned to consume 10 mg/day S-(-)equol ( n=77 women ) or placebo ( n=83 women ) for 12 weeks . Participants completed a st and ardized menopausal symptom checklist and rated five common menopause symptoms by a visual analog scale at baseline , week 12 , and week 18 ( 6-week postintervention ) . Physical , blood , and urine examinations were conducted . One hundred twenty-six women completed the study . RESULTS At baseline , daily hot flush frequency was 2.9±2.1 for the S-(-)equol group and 3.2±2.4 for the placebo group . After the 12-week intervention , the S-(-)equol group had a greater decrease from baseline in hot flush frequency compared with the placebo group ( -1.9±1.8/day , -58.7 % , vs. -1.0±2.0/day , -34.5 % , p=0.009 ) . The severity of hot flushes and neck or shoulder muscle stiffness significantly decreased in the S-(-)equol group compared with the placebo group . No changes in clinical parameters or serious adverse effects were reported . CONCLUSIONS This is the first trial to show beneficial effects of a 10-mg natural S-(-)equol supplement consumed daily for 12 weeks on major menopausal symptoms , specifically , hot flushes and neck or shoulder muscle stiffness , in postmenopausal Japanese women . This supplement offers a promising alternative for management of menopausal symptoms OBJECTIVE To investigate the efficacy-safety balance of the isopropanolic extract of Actaea ( = Cimicifuga ) racemosa ( iCR , Remifemin ) in comparison with tibolone in Chinese women with climacteric complaints . METHOD The r and omized , double-blind , controlled 3-month study in 5 centers of 3 cities in China enrolled 244 menopausal patients aged 40 - 60 years and with a Kupperman Menopause Index (KMI)>or=15 . The participants were assigned to either iCR corresponding to 40 mg crude drug/day ( N=122 ) or tibolone 2.5mg/day ( N=122 ) orally . The primary endpoint was the combination of the Mann-Whitney values ( MWV ) of the KMI and the frequency of adverse events ( benefit-risk balance ) at end of treatment ( MWV>0.5 shows superiority ; MWV>0.36 shows non-inferiority ) . RESULTS KMI decreased from 24.7+/-6.1 to 11.2+/-6.2 and 7.7+/-5.8 ( iCR ) and to 11.2+/-7.2 and 7.5+/-6.8 ( tibolone ) at 4 and 12 weeks . This remarkable and clinical ly relevant improvement was similar in both treatment groups ( MWV=0.47 ; 95 % CI=0.39 - 0.54 ; p(non-inferiority)=0.002 ) showing statistical significant non-inferiority of iCR to tibolone . The KMI-responder rate was similar in both groups ( 84 % and 85 % ) . The safety evaluation showed for both groups a good safety and tolerability profile , however , there is a significant lower incidence of adverse events ( p<0.0001 ) in favor of the herbal treatment . None of the postmenopausal iCR patients experienced vaginal bleeding in contrast to tibolone ( 17 cases ) . Breast and abdominal pain as well as leukorrhea was mostly observed in the tibolone group ( p=0.015 , p=0.008 , p=0.002 ) . No serious adverse event was observed in the iCR-group , however , two occurred in the tibolone-group . The benefit-risk balance for iCR was significantly ( p=0.01 ) superior to tibolone ( MWV=0.56 ; 95 % confidence interval [ 0.51 - 0.62 ] ) . CONCLUSION The efficacy of iCR ( medicinal product Remifemin ) is as good as tibolone for the treatment of climacteric complaints , even for moderate to severe symptoms , whereby iCR is clearly superior regarding the safety profile . This iCR containing medicinal product is an excellent option for treatment of climacteric complaints which has now for the first time been verified in Asian women Objective : To compare the effects of daily ingestion of soy flour ( S ) , ground flaxseed ( F ) , or wheat flour ( W ) muffins , on quality of life and hot flash frequency and severity in postmenopausal women . Design : This was a double-blind , r and omized , controlled , intention-to-treat trial . Ninety-nine women , 1 to 8 years after menopause , ingested muffins with 25 g of flaxseed ( 50 mg of lignans ) , 25 g of soy ( 42 mg of isoflavones ) , or wheat ( control ) daily for 16 weeks . Subjects completed the Menopause-specific Quality of Life instrument monthly along with daily hot flash frequency and severity diaries . Compliance measures included a 3-day food diary and urinary isoflavone and lignan analyses at weeks 0 and 16 and returned muffin counts monthly . Results : Eighty-seven women ( 28 , ground flaxseed muffins ; 31 , soy flour muffins ; and 28 , wheat flour muffins ) completed the trial . Multivariate analysis of variance of all quality -of-life domains yielded an insignificant treatment × time interaction ( F46,122 = 0.92 , P = 0.62 ) but a significant time main effect ( P < .0001 ) . Repeated- measures analyses of covariance controlling for body mass index showed no significant group × time interaction nor time nor group differences on all quality -of-life domains and hot flash measures except severity . Hot flashes were less severe with flaxseed ( P = 0.001 ) compared to placebo ; however , the group × by time interaction was not significant . Phytoestrogen excretion analysis showed treatment group exposure as allocated and no contamination . Conclusion : Neither dietary flaxseed nor soy flour significantly affected menopause-specific quality of life or hot flash symptoms in this study Objective The goal of this study was to evaluate the efficacy and safety of gastroretentive gabapentin ( G-GR ) for the treatment of moderate-to-severe menopausal hot flashes . Methods The primary endpoints of this r and omized , placebo-controlled study of G-GR ( 600 mg am/1,200 mg pm ) were the mean daily frequency and severity of hot flashes at weeks 4 and 12 . Secondary endpoints included Patients ’ Global Impression of Change , Clinicians ’ Global Impression of Change , and daily sleep interference at week 24 . Results Six hundred women with 7 or more moderate-to-severe hot flashes/day enrolled ; 66.2 % completed 24 weeks of treatment . At weeks 4 and 12 , G-GR – treated women experienced significantly greater reductions in mean hot flash frequency and severity than placebo-treated women ( frequency : week 4 , −1.7 , P < 0.0001 ; week 12 , −1.14 , P = 0.0007 ; severity : week 4 , −0.21 , P < 0.0001 ; week 12 , −0.19 , P = 0.012 ) . Similar reductions were maintained up to week 24 . On the Patient Global Impression of Change , more women receiving G-GR than placebo were “ much ” or ” very much ” improved ( week 12 : 58 % vs 44 % , P = 0.0008 ; week 24 : 76 % vs 55 % , P < 0.0001 ) . G-GR significantly reduced sleep interference compared with placebo at week 12 ( P = 0.0056 ) and week 24 ( P = 0.0084 ) . Approximately 5 % more women taking G-GR withdrew because of adverse events ( G-GR/placebo , 16.7%/11.5 % ) . The most common adverse events were dizziness ( 12.7%/3.4 % ) , headache ( 9.3%/8.1 % ) , and somnolence ( 6.0%/2.7 % ) ; incidences dropped to sustained low levels after a few weeks . Conclusions G-GR is a modestly effective nonhormone therapy option for the treatment of moderate-to-severe hot flashes due to menopause and is well tolerated with titration OBJECTIVES The aim of this study was to demonstrate that the therapeutic efficacy of an estradiol 1mg/drospirenone 2 mg ( E2/DRSP ) preparation is superior to a placebo in postmenopausal Korean women with hot flushes and other climacteric symptoms , and to demonstrate that this treatment is both safe and tolerable . METHODS This was a double-blind , r and omized , placebo-controlled , multicenter study over four 28-day treatment cycles . A total of 158 subjects were screened and 90 women were r and omized into two treatment groups ( E2/DRSP group , n=45 ; placebo group , n=45 ) . The primary efficacy parameter was the individual relative change of hot flushes . The secondary efficacy parameters such as other climacteric , urogenital symptoms and vaginal bleeding patterns were also evaluated , and the occurrence of any adverse events was noted . In addition , physical , gynecological examinations and laboratory analyses were performed at the beginning and end of the study . RESULTS The mean number of hot flushes per week during treatment weeks 3 - 16 decreased by 48.1 % during treatment with placebo , and by 84.4 % during treatment with E2/DRSP ( p<0.001 ) . The E2/DRSP combination also reduced the incidence and intensity of menopausal symptoms in postmenopausal women . Most of adverse events was mild or moderate degree of intensity . None of the parameters measured in the study , including laboratory analyses , physical and gynecological examinations , vital signs , and weight , led to any concerns of safety . CONCLUSIONS The E2 1mg/DRSP 2 mg combination tested in the study was efficacious and safe in the treatment of hot flushes and other climacteric symptoms in postmenopausal Korean women OBJECTIVE To examine the efficacy and tolerability of a new matrix patch delivering estradiol ( E2 Matrix ) at doses of 0.05 and 0.10 mg per day ( Estraderm MX 50 , 100 ) in the treatment of moderate to severe postmenopausal symptoms . METHODS A total of 254 postmenopausal women were r and omized to receive treatment with E2 Matrix 0.10 mg ( N = 86 ) , E2 Matrix 0.05 mg ( N = 82 ) , or placebo ( N = 86 ) in a double-blind , double-dummy fashion for a period of 12 weeks continuously . Patches were applied twice weekly to the buttocks with each patient wearing two patches at all times . The primary efficacy criterion was the difference from baseline of the mean number of moderate to severe hot flushes per 24 h during the last 2 weeks of treatment . Other efficacy variables included reduction in hot flushes at 4 and 8 weeks , reduction in daytime flushing and night sweats , and Kupperman Index at 4 , 8 , and 12 weeks . RESULTS E2 Matrix 0.10 and 0.05 mg were both significantly superior to placebo in reducing hot flushes per 24 h after 4 , 8 , and 12 weeks of treatment ( P < 0.001 ) . Also , for all other efficacy parameters studied , both dosage strengths of E2 Matrix were statistically significantly superior to placebo at all time points ( P < 0.001 ) . Local tolerability was good in both groups . A slight increase in estrogen related adverse effects ( breast tenderness , leukorrhoea ) was seen with the 0.10 mg patch . Adhesion of patches and compliance were good . Overall systemic tolerability was good in both treated groups . However , a 4.8 % overall incidence of endometrial hyperplasia was observed in patients with an intact uterus . CONCLUSIONS This new matrix patch offers an effective and well tolerated dosage form for delivery of 0.05 and 0.1 mg estradiol per day . It may be particularly suitable for those women who experience local sensitivity to alcohol-containing systems . In light of the observed hyperplasia after treatment in five patients , estrogen therapy should as yet be supplemented monthly with a progestogen in women with an intact uterus Objective This study aims to determine the efficacy and tolerability of omega-3 fatty acids in reducing vasomotor symptoms ( VMS ) frequency and bother in perimenopausal and postmenopausal women . Methods This study was a 12-week , three-by-two factorial , r and omized controlled trial . Eligible women were r and omized to a double-blind comparison of omega-3 ( n = 177 ) or placebo ( n = 178 ) capsules , and simultaneously to yoga ( n = 107 ) , aerobic exercise ( n = 106 ) , or their usual physical activity ( n = 142 ) . Participants received 1.8 g of omega-3 daily for 12 weeks . Each capsule contained ethyl eicosapentaenoic acid ( 425 mg ) , docosahexaenoic acid ( 100 mg ) , and other omega-3s ( 90 mg ) . Primary outcomes were VMS frequency and bother . Secondary outcomes included sleep quality ( Pittsburgh Sleep Quality Index ) , insomnia symptoms ( Insomnia Severity Index ) , depressive symptoms ( Physician ’s Health Question naire-8 ) , and anxiety ( Generalized Anxiety Disorder-7 ) . Results The mean baseline frequency of VMS per day was 7.6 ( 95 % CI , 7.0 to 8.2 ) . After 12 weeks , the reduction in VMS frequency with omega-3 ( −2.5 ; 95 % CI , −3.0 to −1.9 ) did not differ significantly from that with placebo ( −2.7 ; 95 % CI , −3.3 to −2.2 ) , with a relative difference of 0.3 fewer hot flashes per day ( 95 % CI , −0.5 to 1.0 ; P = 0.28 ) . Changes in VMS bother at 12 weeks were also similar between groups , with no relative difference on a four-point scale ( 95 % CI , −0.1 to 0.2 ; P = 0.36 ) . Omega-3s compared with placebo showed no improvement in self-reported sleep or mood ( P > 0.09 for all comparisons ) . Conclusions Among healthy , sedentary perimenopausal and postmenopausal women , a 12-week treatment with omega-3 does not improve VMS frequency , VMS bother , sleep , or mood compared with placebo Objective : The aim of this study was to evaluate the efficacy of citalopram for climacteric symptoms and to assess the combined effect of citalopram and hormone therapy ( HT ) on climacteric symptoms in women inadequately responsive to HT alone . Design : The study included 100 postmenopausal women who were allocated into one of four groups : ( 1 ) citalopram , ( 2 ) placebo , ( 3 ) citalopram + HT , or ( 4 ) placebo + HT . The women who were unable or unwilling to take HT were r and omly placed in groups 1 and 2 . The women who were inadequately responsive to HT were r and omly placed in groups 3 and 4 . The initial dose of citalopram was 10 mg/day in groups 1 and 3 . After 1 week , the dose was increased to 20 mg/day . After starting the medication , follow-up visits took place during the fourth and eighth weeks of treatment . During the first and eighth weeks , women completed two question naires : a modified Kupperman index and the Menopause-Specific Quality of Life Question naire . Results : Mean hot flash scores significantly improved in all groups ( P < 0.05 ) . The reduction rates were 37 % in group 1 , 13 % in group 2 , 50 % in group 3 , and 14 % in group 4 . Psychosocial complaints and mean values on the Kupperman index significantly decreased in all groups ( P < 0.05 ) . Physical well-being significantly improved in groups 1 , 3 , and 4 ( P < 0.05 ) . The decrease in all scores was significantly greater in groups 1 and 3 compared to groups 2 and 4 ( P < 0.01 ) . Conclusion : Citalopram is an effective alternative treatment option for patients who do not want to take HT for the alleviation of climacteric symptoms . Adjuvant treatment with a selective serotonin reuptake inhibitor increases the effectiveness of HT for the treatment of climacteric symptoms in women who had responded inadequately to HT OBJECTIVES To evaluate the safety and efficacy of Menorest 50 in two clinical trials . METHODS Menorest 50 was evaluated in two trials : the first was a parallel-group , r and omized double-bind study vs. Premarin 0.625 mg/day in 214 women while the second was a parallel-group , open-label trial versus Estraderm TTS 50 in 205 women . RESULTS In both studies there was a significant decrease in the mean number of hot flushes/day compared with baseline but no significant differences between treatments . The severity of hot flushes and the incidence and severity of other menopausal symptoms such as sweats , palpitations , headaches , depression , tiredness , vaginitis , loss of libido and dyspareunia were reduced to the same extent by all treatments . There were no significant differences between the different treatments as far as serum oestradiol or the incidence of systemic adverse events were concerned . In addition , small positive effects of total cholesterol and high-density lipoproteins were observed in the first study . Only a small reduction in cholesterol was seen in the second study in both groups but Menorest appeared to be better tolerated and a lower incidence of erythema , pruritus and other topic adverse events was reported . In addition , the twice-weekly application of Menorest was found to be convenient . CONCLUSIONS Menorest appears to be as equally effective as oral and transdermal oestradiol as far as reduction in the incidence and severity of menopausal symptoms is concerned . It was safe and also better tolerated than Estraderm OBJECTIVE To evaluate the effects of treatment with Trifolium pratense on climacteric symptoms and sexual satisfaction in postmenopausal women . METHODS This is a prospect i ve , r and omized , double-blind , placebo-controlled study . Initially , 120 women aged 45 - 65 years with menopausal symptoms , more than 12-month amenorrhea and no treatment in the past six months were selected . The participants were then divided into two groups : TG – receiving 40 mg Trifolium pratense , 1 capsule/day ; PG – receiving placebo capsules containing lactose ( control ) , 1 capsule/day . The duration of treatment was 12 months . The patients underwent clinical and laboratory evaluation before treatment and at four , eight and 12 months of treatment . The Kupperman Menopausal Index and the Golombok Rust Inventory of Sexual Satisfaction ( GRISS ) were used . At the end of the study , each group comprised 50 patients . RESULTS According to the Kupperman Menopausal Index , there was significant improvement in menopausal symptoms after four months of treatment , especially in relation to hot flashes , when compared to baseline data in both groups . However , no significant differences were observed between groups . There was no improvement in sexual satisfaction after treatment . CONCLUSION A 12-month treatment with a daily dose of 40 mg Trifolium pratense did not yield a significant improvement in menopausal symptoms and sexual satisfaction Objective To evaluate the effect on climacteric symptoms and quality of life , and the safety of four doses of progestelle progesterone cream administered for 24 weeks to postmenopausal women complaining of moderate to severe menopausal symptoms . Design Single-centre , double-blind , r and omized , placebo-controlled study . Population Two hundred and twenty-three healthy postmenopausal women , aged between 40 and 60 years and complaining of severe menopausal symptoms were recruited through newspaper advertisements . Methods Women were r and omly allocated to progestelle progesterone cream 60 , 40 , 20 , 5 mg or placebo , to be applied daily for six months . Main outcome measures The primary efficacy variable was the psychological , somatic and vasomotor components of the Greene Climacteric Scale after six months . Secondary endpoints were incidence of hot flushes and night sweats , the nine subscales of the Medical Outcome Survey Short Form-36 ( SF-36 ) , serum progesterone , endometrial thickness and histology after six months . Adverse events were sought and recorded and followed up to resolution . Results There were no statistically significant differences between any of the treatment groups and placebo for any of the components of the Greene Score . A statistically significant difference between the 20 mg group and placebo was found for the physical functioning ( 95 % confidence interval [ CI ] 1.7–12.3 ; P = 0.01 ) and social functioning ( 95 % CI 1.9–16.7 ; P = 0.01 ) scales of SF-36 after six months . No other statistically significant differences were found between any treatment group and placebo for any of the other secondary efficacy variables . There appeared to be a higher incidence of headache in the groups treated with progesterone cream . Conclusions Progesterone cream was no more effective than placebo for relief of menopausal symptoms Objective : Nonhormonal treatment of postmenopausal symptoms is a subject of great interest today . The results of studies on selective serotonin reuptake inhibitors ( SSRIs ) are promising , but long-term results do not exist . The objective of this study was to evaluate the efficacy of citalopram and fluoxetine in the treatment of physical and psychological menopausal symptoms and their effects on psychosocial and sexual well being in symptomatic postmenopausal women . Design : One hundred fifty healthy women suffering from menopausal symptoms were recruited to this placebo-controlled double-blind study with a follow-up period of 9 months . They were r and omized into three groups receiving placebo , fluoxetine , or citalopram . The initial dose was 10 mg of both fluoxetine and citalopram , and it was increased to 20 mg at 1 month and to 30 mg at the 6-month visit . The main outcome measures were hot flushes and Kupperman index . The R AND -36 Quality of Life question naire , Beck 's Depression Scale , and the McCoy Female Sexuality Question naire were used at every control visit . Results : There were no statistically significant differences between the groups in respect to number of hot flushes , Kupperman index , or Beck 's Depression Scale , although there was a tendency in all these parameters in favor of SSRIs versus placebo . Insomnia improved significantly in the citalopram group versus placebo . Discontinuation rates at nine months were 40 % in the placebo group , 34 % in the fluoxetine group and 34 % in the citalopram group . Conclusions : Compared with placebo , citalopram and fluoxetine have little effect on hot flushes and can not therefore be recommended for the treatment of menopausal symptoms , if vasomotor symptoms are the main complaint . Whether the improvement of insomnia by means of citalopram affects the quality of sleep needs further investigation ABSTRACT Objective To evaluate the efficacy and safety of desvenlafaxine ( administered as desvenlafaxine succinate ) vs. tibolone and placebo for menopausal vasomotor symptoms and the incidence of uterine bleeding . Methods This 12-week , double-blind , r and omized , controlled trial was conducted at 35 sites in Europe , two sites in South Africa , and one site in Mexico . Postmenopausal women with ≥50 moderate or severe hot flushes per week ( n = 485 ) were r and omized to desvenlafaxine 100 mg/day , tibolone 2.5 mg/day , or placebo . Reduction in the average daily number of moderate and severe hot flushes at weeks 4 and 12 ( primary endpoint ) was evaluated using analysis of covariance . Safety assessment s included incidence of uterine bleeding , adverse events , laboratory values , and vital signs . Results At week 12 , no statistically significant difference was observed in reduction of the average daily number of moderate and severe hot flushes for desvenlafaxine ( −5.78 ) vs. placebo ( −5.82 ; p = 0.921 ) , although time to 50 % reduction was significantly less than placebo ( 13 vs. 26 days , p = 0.006 ) . Hot flush reduction with tibolone ( −8.21 ) was significantly greater than placebo ( p < 0.001 ) . Nausea was the most common adverse event with desvenlafaxine , was generally mild to moderate , and resolved within the first 2 weeks . Significantly more subjects experienced bleeding with tibolone ( 23 % ) vs. desvenlafaxine ( 12 % ; p < 0.024 ) or placebo ( 9 % ; p < 0.001 ) . Conclusions Desvenlafaxine did not separate from placebo in reducing the number of moderate to severe hot flushes at week 12 , although it did allow women to achieve 50 % reduction sooner than placebo . Tibolone did separate from placebo , but with smaller than expected effect . The placebo effect was high ( 57 % ) . Adverse drug reactions were consistent with the known safety profile of desvenlafaxine , and significantly more women who received tibolone experienced episodes of bleeding compared with women who received desvenlafaxine or placebo OBJECTIVE To evaluate the effects of escitalopram 10 - 20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes . STUDY DESIGN A double-blind , placebo-controlled r and omized trial of escitalopram 10 - 20mg/day vs. identical placebo was conducted among 205 women ages 40 - 62 years with an average of ≥4 daily hot flashes recruited at 4 clinical sites from July 2009 to June 2010 . MAIN OUTCOME MEASURES The primary trial outcomes , reported previously , were the frequency and severity of vasomotor symptoms at 8 weeks . Here , we report on the pre-specified secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Question naire ( MENQOL ) and the pain intensity and interference scale ( PEG ) . RESULTS Outcome data were collected on 97 % of r and omized women and 87 % of women took at least 70 % of their study medication . Treatment with escitalopram result ed in significantly greater improvement in total MENQOL scores ( mean difference at 8 weeks of -0.41 ; 95 % confidence interval ( CI ) -0.71 to -0.11 ; p<0.001 ) , as well as Vasomotor , Psychosocial , and Physical domain scores with the largest difference seen in the Vasomotor domain ( mean difference -0.75 ; 95 % CI -1.28 to -0.22 ; p=0.02 ) . There was no significant treatment group difference for the Sexual Function domain . Escitalopram treatment result ed in statistically significant improvements in PEG scores compared to placebo ( mean treatment group difference at 8 weeks of -0.33 ; 95 % CI -0.81 to 0.15 ; p=0.045 ) . CONCLUSIONS Treatment with escitalopram 10 - 20mg/day in healthy women with vasomotor symptoms significantly improved menopause-related quality of life and pain OBJECTIVE To compare the effect of transdermal estradiol-17 beta and oral conjugated equine estrogen when combined with an oral progestin on quality of life in post-menopausal women . DESIGN R and omized controlled double-blind trial . A r and omization error lead to the exclusion of six subjects but the soundness of the remaining r and omization was confirmed . SETTING Large urban community . PATIENTS Women 2 - 7 years after menopause with a uterus and ovaries , and not currently using hormone replacement therapy . Seventy-four women completed the trial . INTERVENTIONS After baseline measures of quality of life , subjects were r and omly assigned to either continuous oral conjugated equine estrogen 0.625 mg daily or continuous transdermal estradiol-17 beta 50 mcg twice weekly , for four 4-week cycles . Medroxyprogesterone acetate 10 mg oral tablets was administered to both groups for the last 12 days of each cycle . OUTCOMES MEASURED Quality of life was determined using the Menopause-Specific Quality of Life Question naire . Tolerability was determined by a specifically design ed list of adverse effects . Both measures were recorded at base-line and in mid-cycle during the second , third and fourth cycles of treatment . RESULTS There were no statistically significant differences in any of the domains at baseline between the oral and transdermal treatment groups . In the vasomotor domain-scores for the oral and transdermal groups improved from baseline levels of 3.14 and 3.09 , respectively , to 1.32 and 1.23 ; physical domain scores improved from 2.45 and 2.73 to 2.04 and 1.78 ; psychosocial domain scores improved from 2.72 and 3.04 to 2.21 and 1.94 ; sexual domain scores improved from 2.32 and 2.16 to 1.64 and 1.30 . There were no statistically significant group differences or time/group interactions . Both forms of therapy were equally well tolerated . CONCLUSIONS Improvement in all domains , measured by the Menopause-Specific Quality of Life Question naire , was observed in both the oral and transdermal groups . In the absence of a placebo control group , the improvements observed can not be attributed solely to the therapy . Neither form of therapy offered an advantage over the other in respect to improvement in quality of life Purpose This study was conducted to investigate the efficacy of black cohosh ( Cimicifuga racemosa ) and St. John 's wort ( Hypericum perforatum ) in women with climacteric symptoms , and to assess their effects on vaginal atrophy , hormone levels , and lipid profiles . Material s and Methods In this double-blind r and omized , placebo-controlled , multicenter study , 89 peri- or postmenopausal women experiencing climacteric symptoms were treated with St. John 's wort and black cohosh extract ( Gynoplus ® ) , Jin-Yang Pharm . , Seoul , Korea ) or a matched placebo for 12 weeks . Climacteric complaints were evaluated by the Kupperman Index ( KI ) initially and at 4 and 12 weeks following treatment . Vaginal maturation indices , serum estradiol , FSH , LH , total cholesterol , HDL-cholesterol , LDL-cholesterol , and triglyceride levels were measured before and after treatment . From the initial 89 participants , 77 completed the trial ( 42 in the Gynoplus group , 35 in the placebo group ) . Results Baseline characteristics were not significantly different between the two groups . Mean KI scores and hot flushes after 4 and 12 weeks were significantly lower in the Gynoplus group . Differences in superficial cell proportion were not statistically significant . HDL levels decreased in the control group from 60.20 ± 16.37 to 56.63 ± 12.67 , and increased in the Gynoplus group from 58.32 ± 11.64 to 59.74 ± 10.54 ; this was statistically significant ( p = 0.04 ) . Conclusion Black cohosh and St. John 's wort combination was found to be effective in alleviating climacteric symptoms and might provide benefits to lipid metabolism ABSTRACT Objective To evaluate the efficacy and safety of a complex remedy compared with placebo to treat menopausal symptoms . Methods A total of 102 peri- and postmenopausal women requiring treatment for menopausal symptoms were r and omized to receive a complex anthroposophic remedy prepared in the homeopathic manner ( Apis regina tota GL D4 , Argentum metallicum D5 , Ovaria bovis GL D4 ) , 3 × 10 globuli daily ( 2 × 12 weeks ) and placebo ( 12 weeks ) in different orders of remedy ( R ) and placebo ( P ) ( 1 : R/R/P , 2 : P/R/R , 3 : R/P/R ) . The primary endpoint was change in climacteric symptoms assessed by the Menopause Rating Scale II ( MRS II ) after 12 weeks . Secondary endpoints were changes of symptoms and safety throughout the study . Results Reduction of symptoms after 12 weeks did not differ between remedy and placebo ( total score MRS II : –1.4 , 95 % confidence interval ( CI ) −2.8 to 0 vs. −2.3 , 95 % CI −4.4 to −0.3 , p = 0.441 ) and had no clinical relevance ( defined as reduction in MRS II ≥ −3.5 ) . Comparison of secondary outcomes at 12 weeks between remedy and placebo or between groups after the 2nd or 3rd period compared to previous periods did not differ . Treatment with remedy for 24 consecutive weeks did not reach clinical relevance either . However , total reduction of symptoms after three periods in Group 1 ( R/R/P ) ( −5.0 , 95 % CI −7.5 to −2.5 ) and Group 2 ( P/R/R ) ( −5.9 , 95 % CI −8.7 to −3.1 ) reached clinical relevance whereas almost no decrease of symptoms after three periods was seen in Group 3 ( R/P/R ) ( −0.5 , 95 % CI −2.9 to 1.9 ) . Conclusions Treatment with the complex remedy for 12 or 24 weeks did not result in clinical ly significant improvement of menopausal symptoms OBJECTIVE This study aim ed to evaluate the efficacy of Hop on early menopausal symptoms and hot flashes . METHODS In this r and omized controlled trial , 120 women were r and omly allocated into two groups , receiving the Hop or placebo tablets for 12 weeks . Early menopausal symptoms were assessed using Greene scale and hot flashes were recorded in a diary before , and 4 , 8 and 12 weeks after intervention . RESULTS The mean Greene score was significantly lower in the Hop group than the placebo group at the end of weeks 4 ( adjusted difference : -10.0 , 95 % confidence interval : -11.1 - -8.9 ) , 8 ( -18.6 , -20.1 - -17.1 ) and 12 ( -23.4 , -25.1 - -21.6 ) . The number of hot flashes was significantly lower in the Hop group than the control group during the weeks 4 ( -8.4 , -9.8 - -7.1 ) , 8 ( -17.1 , -14.9 - -19.3 ) and 12 ( -23.8 , -21.1 - -26.4 ) . CONCLUSIONS Hop effectively reduced the early menopausal symptoms . CLINICAL TRIAL REGISTRATION This study was approved ( code 91209 ) by the Ethic Committee of Tabriz university of Medical Sciences and registered at the Iranian registry of clinical trials , with I RCT 2013010110324N7 on April 2013 Objective : To evaluate the effectiveness of a phytotherapeutic intervention comprising a combination of Hypericum perforatum ( St. John 's wort ) and Vitex agnus-castus ( Chaste tree/berry ) in the management of menopausal symptoms . Design : A double-blind , r and omized , placebo-controlled , parallel trial was performed over 16 weeks in 100 eligible late-perimenopausal or postmenopausal women experiencing hot flushes and other menopausal symptoms . Herbal combination therapy or placebo tablets were administered twice daily . The primary endpoint was hot flush episodes . Secondary endpoints included Greene Climacteric Scale scores , Hamilton Depression Inventory scores , and Utian Quality of Life Scale scores . Results : Ninety-three women completed the study . Data analysis on an intent-to-treat basis found no significant differences between the two groups for any of the endpoints . Analyses performed at interim data time points revealed no significant differences at week 4 , 8 , or 12 for daily weighted flushes or scores on the Greene Climacteric Scale or Hamilton Depression Inventory . However , significant improvements across the treatment phase were observed in both the placebo and active treatment groups for these endpoints . No significant change was found for either group on quality of life . Conclusion : The herbal combination of H. perforatum and V. agnus-castus was not found to be superior to placebo for the treatment of menopausal symptoms . The herbal combination was well tolerated with no significant adverse events noted in the short term . Robust findings from quality studies such as this are important for informing the community , healthcare providers , and regulatory authorities Abstract Objective : This study aim ed to evaluate the effect of health education combining diet and exercise supervision on menopausal symptoms and diet/exercise habits . Methods : The r and omized controlled study enrolled 60 patients with perimenopausal syndrome ( Kupperman Menopause Index ( KMI ) score ≥15 ) . The participants were r and omized into either an intervention group ( n = 30 ) or a control group ( n = 30 ) . Women were interviewed with question naires about perimenopausal symptoms , diet pattern and exercise habit . Their height and weight were measured . Women in the intervention group received health education , diet supervision and exercise supervision twice a week while those in the control group continued as normal . The total KMI score , scores of individual symptoms , diet pattern and exercise habit were measured after intervention . Results : The total KMI score , the individual KMI scores for paresthesia , irritability , depression/suspicious , fatigue , arthralgia/myalgia , and palpitations of the intervention group were significantly lower compared with the control group after intervention . The intake of cereal , meat , fats and oils of the intervention group were significantly lower at week 12 compared with baseline . The percentage of women with a regular exercise habit was significantly higher in the intervention group than in the control group after intervention . Conclusions : Twelve weeks intervention of health education combining diet and exercise supervision could improve perimenopausal symptoms and help the patients establish good living habits Objective : This study compared the effectiveness of individualized acupuncture plus self-care versus self-care alone on hot flashes and health-related quality of life in postmenopausal women . Methods : This study involved a multicenter , pragmatic , r and omized , controlled trial with two parallel arms . Participants were postmenopausal women experiencing , on average , seven or more hot flashes per 24 hours during seven consecutive days . The acupuncture group received 10 acupuncture treatment sessions and advice on self-care , and the control group received advice on self-care only . The frequency and severity ( 0 - 10 scale ) of hot flashes were registered in a diary . Urine excretion of calcitonin gene-related peptide was assessed at baseline and after 12 weeks . The primary endpoint was change in mean hot flash frequency from baseline to 12 weeks . The secondary endpoint was change in health-related quality of life measured by the Women 's Health Question naire . Results : Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group ( n = 134 ) and 3.7 per 24 hours in the control group ( n = 133 ) , a difference of 2.1 ( P < 0.001 ) . Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group , a difference of 1.4 ( P < 0.001 ) . The acupuncture group experienced statistically significant improvements in the vasomotor , sleep , and somatic symptoms dimensions of the Women 's Health Question naire compared with the control group . Urine calcitonin gene-related peptide excretion remained unchanged from baseline to week 12 . Conclusions : Acupuncture plus self-care can contribute to a clinical ly relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women Objective . Continuous combined hormone replacement therapy ( ccHRT ) based on estradiol valerate ( E2V ) and medroxyprogesterone acetate ( MPA ) is effective for relief of menopausal symptoms three years or more after the menopause . This study was undertaken to examine the efficacy and tolerability of ccHRT in early postmenopausal women ( last menstrual period 1.3 years before study entry ) . Study design . This was a 52-week , r and omized , double-blind , multinational study of ccHRT comprising three different dose combinations of E2V/MPA in 459 early postmenopausal non-hysterectomized women experiencing 30 or more moderate to severe hot flushes a week and /or vasomotor symptoms requiring treatment . Main outcomes measures . The primary endpoint was change in frequency and severity of moderate to severe hot flushes at 12 weeks . Secondary outcome measures included number of bleeding days and evaluation of tolerability . Results . The frequency of hot flushes was reduced by ≥70 % after one month ( P<0.001 for all doses at week 2 onwards ) , with little evidence of statistically different dose effects . Severity of flushing was also attenuated by ccHRT . Mean number of bleeding days fell to < 1 per 28-day cycle at 52 weeks . Rates of amenorrhoea approached 80–90 % at the end of the study , but were significantly lower at several time points with the highest-dose regimen ( 2 mg E2V + 5 mg MPA ) than with the lower-dose options ( 1 mg E2V + 2.5 mg MPA and 1 mg E2V + 5 mg MPA ; P<0.05 ) . Adverse events declined in frequency over time with all regimens but throughout the study were more numerous with the highest-dose regimen than with lower doses ( P= 0.0002 ) . Conclusions . Continuous combined HRT was effective for the relief of climacteric symptoms in early postmenopausal women and was well tolerated Objective : To demonstrate the safety and efficacy of tibolone ( 1.25 and 2.5 mg ) in the treatment of moderate to severe vasomotor symptoms and symptoms associated with vaginal atrophy . Design : A placebo-controlled , double-blind , r and omized , multicenter study was conducted on 396 healthy postmenopausal women experiencing a minimum of 7 moderate to severe hot flashes per day ( 60 per week ) . Participants were r and omized to receive tibolone 1.25 or 2.5 mg or placebo once daily for 12 weeks . Assessment s were done at weeks 4 , 8 , and 12 . The severity and frequency of hot flashes were recorded in patient diaries on a daily basis . Results : Tibolone 2.5 mg significantly ( P < 0.001 ) reduced the average number of hot flashes compared with placebo at week 4 ( −7.82 vs −5.27 ) , week 8 ( −9.71 vs −5.86 ) , and week 12 ( −10.14 vs −5.85 ) . The difference between tibolone 1.25 mg and placebo was significant ( P < 0.001 ) at week 8 ( −7.96 ) and week 12 ( −8.32 ) . Findings for the average daily severity of hot flashes were similar , with significantly greater reductions at week 4 ( P < 0.05 ) and weeks 8 and 12 ( P < 0.001 ) for tibolone 2.5 mg versus placebo and at weeks 8 and 12 for tibolone 1.25 mg versus placebo ( P < 0.001 ) . A menopausal atrophic symptom question naire revealed that tibolone 2.5 mg significantly ( P < 0.05 ) reduced nocturia compared with placebo at weeks 4 , 8 , and 12 and urinary urgency at week 4 . Compared with placebo , both doses of tibolone also significantly ( P < 0.001 ) increased the vaginal maturation value from baseline . The overall incidence of adverse events was similar in all treatment groups . Conclusions : Tibolone is effective and well tolerated for the treatment of moderate to severe vasomotor symptoms and the effects of vaginal atrophy associated with menopause Objective Preliminary data suggest that flaxseed , a rich source of dietary lignans , may be a potentially effective treatment of hot flashes . A phase III , r and omized , placebo , controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes . Methods Postmenopausal women with or without breast cancer were r and omly assigned to a flaxseed bar ( providing 410 mg of lignans ) for 6 weeks versus a placebo bar . Participants completed daily , prospect i ve , hot flash diaries during the baseline week , and then ate one study bar per day for 6 weeks while recording their daily hot flashes . The intraparticipant difference in hot flash activity between baseline and the last treatment week was the primary endpoint . Adverse effects were evaluated through a self-report and the Common Terminology Criteria assessment . Results A total of 188 women were enrolled in this trial . The mean hot flash score was reduced 4.9 in the flaxseed group and 3.5 in the placebo group ( P = 0.29 ) . In both groups , slightly more than a third of the women received a 50 % reduction in their hot flash score . Only one adverse effect was significantly different between groups , grade 1 pruritus , which was more common in the placebo group ( 8 % vs 1 % ) . Both groups reported abdominal distension , flatulence , diarrhea , and nausea . Adherence and ability to detect treatment assignment did not differ between groups . Conclusions The results of this trial do not support the use of 410 mg of lignans for the reduction of hot flashes . The bars were fairly well tolerated , with both groups reporting gastrointestinal effects , probably due to the fiber content Method A r and omized , placebo-controlled trial was conducted to evaluate the safety and efficacy of drospirenone ( 1 , 2 or 3 mg ) combined with estradiol ( 1 mg ) in the treatment of climacteric symptoms in healthy postmenopausal women . Results The frequency of hot flushes was significantly decreased in all treatment groups ( range 86–90 % ) in comparison to placebo ( 45 % , p ⩽ 0.001 ) and remained suppressed at 16 weeks . Treatment with drospirenone and estradiol also decreased the intensity and severity of sweating , sleep problems , depression , nervousness , and urogenital symptoms . Most adverse events were mild or moderate , with similar rates observed in all groups . No serious adverse events or clinical ly significant laboratory abnormalities attributed to treatment occurred . Conclusion These results demonstrate that the combinations of 1 , 2 , and 3 mg drospirenone with 1 mg estradiol are safe and effective for the treatment of climacteric symptoms Objective : The aim of this study was to evaluate the effectiveness of acupuncture plus usual care for relief of hot flashes and menopause-related symptoms compared with usual care alone in perimenopausal or postmenopausal women . Methods : A multicenter , r and omized , controlled trial was conducted . Perimenopausal or postmenopausal women with average hot flash scores of 10 or higher during the week before the screening visit were enrolled and r and omly divided into two groups . The treatment group received 12 sessions of acupuncture and maintained usual care for 4 weeks , whereas the control group underwent usual care alone . Hot flash scores were calculated by multiplying frequency by severity of hot flashes recorded in a daily diary . The primary outcome was the mean change in the average 24-hour hot flash score at week 4 from baseline . The secondary outcome was the mean change in menopause-related symptoms as estimated by the Menopause Rating Scale question naire at week 4 . Follow-up assessment at week 8 was conducted in the treatment group only . Results : The mean change in the average 24-hour hot flash score was −16.57 in the treatment group ( n = 116 ) and −6.93 in the control group ( n = 59 ) , a difference of 9.64 ( P < 0.0001 ) . The total Menopause Rating Scale score , as well as the subscale scores for the psychological , somatic , and urogenital dimensions of menopause , showed significant improvement in the acupuncture group compared with the control group ( P < 0.001 ) . The mean change in the treatment group in the primary outcome was −17.58 at week 8 . Conclusions : Our results suggest that acupuncture in addition to usual care is associated with marked clinical improvement in hot flashes and menopause-related symptoms in perimenopausal or postmenopausal women This double-blind , r and omized , multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol ( E2 ) and 0.5 mg trimegestone ( TMG ) with a st and ard hormone replacement therapy containing estradiol valerate ( E2V ) and norgestrel ( NG ) in the treatment of climacteric symptoms . The study was conducted over 13 cycles , each of 28 days , and involved 634 subjects , of whom 481 completed the study . The primary efficacy variable was the percentage of subjects who showed at least a 50 % reduction from baseline in the mean daily number of hot flushes in cycle 3 . This was observed in 98.5 % of the subjects in the E2 + TMG group and 93.3 % of the subjects in the E2V + NG group ( 95 % confidence interval of the difference , 8.6 , 1.9 ) . Significant differences in favor of the E2 + TMG combination were observed in the reduction in the mean daily number and severity of hot flushes , and in the percentage of subjects who had hot flushes at baseline but no hot flushes during treatment . There were no significant differences between the treatments in the Kupperman index and in urogenital signs or symptoms . Treatment with the E2 + TMG combination was well tolerated and the incidences of adverse events were similar in the two treatment groups . Breast pain was the main adverse event , possibly related to treatment that result ed in discontinuation . The mean number of bleeding days per cycle was significantly lower with the E2 + TMG combination than with the E2V + NG combination . The incidences of endometrial hyperplasia were low and comparable in both treatment groups . It was concluded that the E2 + TMG combination was either equivalent or superior to the E2V + NG combination in the treatment of hot flushes and other climacteric symptoms , and that its bleeding profile was favorable Background . The unexpected results of the Women 's Health Initiative study have decreased the use of conventional hormone therapy ( HT ) , changing physicians ' and patients ' attitudes towards HT and increasing their interest in alternative options . Objective . The present study aim ed to evaluate the effect of isoflavones contained in red clover extracts ( Trifolium pratense ) on menopausal symptoms , lipids and vaginal cytology in menopausal women . Methods . Sixty postmenopausal women aged > 40 years , non-users of HT , with Kupperman index score ⩾15 , were double-blindly r and omized to receive either a commercially available red clover isoflavone supplement ( 80 mg/day ) or placebo for 90 days . Subsequently , after a 7-day washout period , subjects switched to receive the opposite treatment for a further 90 days . Kupperman index score was determined and fasting blood and vaginal cytologic sampling performed at baseline , 90 and 180 days . Results . Fifty-three women ( 88.3 % ) completed the trial . Mean age was 51.3 ± 3.5 years , 69.7 % of the women were aged 50 years or more . There was no significant effect on body mass index , weight or blood pressure after either treatment phase . Baseline Kupperman index score decreased significantly after each treatment phase , with the decrease more pronounced after the isoflavone phase ( baseline : 27.2 ± 7.7 ; after isoflavone : 5.9 ± 3.9 ; after placebo : 20.9 ± 5.3 , p < 0.05 ) . Red clover isoflavone supplementation significantly decreased the rate of menopausal symptoms and had a positive effect on vaginal cytology as expressed by improvement in karyopyknotic , cornification and basal cell maturation indices . Mean total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels also decreased ; however , only the latter was significantly lower compared with placebo . Conclusions . Compared with placebo , red clover isoflavone supplementation in postmenopausal women significantly decreased menopausal symptoms and had a positive effect on vaginal cytology and triglyceride levels Objective . To evaluate the effect of red clover isoflavone supplementation over vasomotor and overall menopausal symptoms in postmenopausal women . Methods . One hundred and nine postmenopausal women aged 40 or more were assigned to r and omly receive either two daily capsules of the active compound ( 80 mg red clover isoflavones , Group A ) or placebo of equal appearance ( Group B ) for a 90-day period . After a washout period of 7 days , medication was crossed over and taken for 90 days more . Daily hot flush and night sweat frequency and overall menopausal symptom intensity ( Kupperman Index ) were measured at baseline , 90 , 97 and 187 days . Results . Daily hot flush/night sweat frequency and Kupperman Index values were similar in both studied groups at baseline . All indices significantly decreased after red clover phase in Group A , corresponding , respectively to a 73.5 % , 72.2 % and 75.4 % average decrement . These decrements were significantly higher than those observed for Group B after placebo phase ( 8.2 % , 0.9 % and 6.7 % respectively ) . In Group A , after washout and placebo phases all values significantly increased . In Group B , all indices remained similar after placebo and washout phases , however significantly dropping after red clover treatment . These values were also significantly lower than those observed in Group A after placebo phase . No side effects were encountered after treatment with the active compound or placebo . Conclusion . Red clover isoflavone supplementation was more effective than placebo in reducing daily vasomotor frequency and overall menopausal intensity in postmenopausal women This 12-week , double-masked , double-dummy , r and omized , parallel-group study compared the efficacy and safety of an estradiol matrix transdermal delivery system ( Alora ) in two strengths ( 50-microgram/d estradiol and 100-microgram/d estradiol ) with placebo in postmenopausal women who were experiencing at least 60 moderate-to-severe hot flushes per week . In 273 postmenopausal women , the reduction in the frequency of moderate-to-severe hot flushes was significantly better than placebo within 2 weeks of initiating therapy in the 100-microgram/d group and within 3 weeks of initiating therapy in the 50-microgram/d group . The reduction in hot flushes for both active treatment groups remained significantly different from placebo throughout the 12-week trial . Improvement in vaginal cytology profile ( maturation index ) was observed in both active treatment groups . Serum estradiol concentrations were elevated to early-to mid-follicular levels , in proportion to dose , and the estradiol/estrone ratio remained within the expected premenopausal range . The incidence of estrogen-related side effects was modest but greater in the active treatment groups than in the placebo group : Breast pain was reported in 4.5 % of the patients in the 50-microgram/d group , 5.3 % of patients in the 100-microgram/d group , and none of the patients in the placebo group . Breakthrough bleeding occurred in 3.4 % of women in the 50-microgram/d group , 20.2 % of women in the 100-microgram/d group , and 4.4 % of women in the placebo group . Only 3 ( 1.1 % ) patients terminated treatment because of skin reactions . This study demonstrates that this estradiol matrix transdermal delivery system is effective in the treatment of menopausal symptoms , while providing the skin tolerability desired by patients Objective : To evaluate the effectiveness of a formula containing Chinese herbs and Cimicifuga racemosa in alleviating vasomotor symptoms and improving quality of life . Methods : Between September 2004 and October 2005 , 93 healthy women aged 45 to 65 years who reported six or more vasomotor symptoms per 24 hours were recruited into a 20-week r and omized , double-blind , placebo-controlled trial . Women were consulted in clinics conducted within the Sydney metropolitan area . After a 4-week baseline period , women were r and omly allocated to receive herbal ( equivalent to 3,150 mg dry herb ) or identical placebo tablets for 16 weeks . Women recorded the number and severity ( 1 = mild to 4 = very severe ) of vasomotor symptoms in a daily hot flash diary and completed the Greene Climacteric and Hot Flash Related Daily Interference scales at each monthly consultation . Results : Intention-to-treat and per- protocol analyses found no statistically significant differences in mean hot flash scores ( product of frequency and intensity ) , Greene Climacteric Scale scores , and Hot Flash Related Daily Interference Scale scores between the placebo and herbal treatment groups after 16 weeks of intervention . Conclusions : This herbal formula containing Chinese herbs and Cimicifuga can not be recommended to alleviate menopausal vasomotor symptoms or improve quality of life Objective Paced breathing ( slow , deep , diaphragmatic breathing ) reduces central sympathetic activity and facilitates the relaxation response . The present study was design ed to assess the feasibility of and to obtain initial efficacy estimates of two paced-breathing programs , compared with usual breathing , for the frequency and severity of hot flashes . Methods We design ed a 9-week , r and omized , three-arm , parallel-group , blinded ( investigator ) phase II clinical trial . Using an audio CD , participants in the active arms practice d paced breathing at 6 breaths/minute for 15 minutes , either once or twice a day , whereas the control arm practice d usual breathing at 14 breaths/minute for 10 minutes/day . Feasibility was assessed through self-report question naires ; percent reduction and effect size estimates were determined using changes in hot flash frequency and scores within each group . Results Of the 92 eligible participants , 68 ( 74 % ) completed the study . Most women reported that the intervention was easy to do ( 79 % ) and of appropriate duration ( 71 % ) . They could practice exercises as taught ( 61 % ) and could practice on most days ( 65 % ) . Participants in all arms reported hot flash reductions during the 9 weeks : 52 % for paced breathing twice a day , 42 % for paced breathing once a day , and 46 % for usual breathing . Conclusions The paced-breathing intervention is feasible . Although paced breathing twice a day seems to be the most helpful dose , efforts to intensify paced breathing once a day may be more practical for widespread dissemination . The efficacy and overall clinical impact of paced-breathing exercises on hot flash reduction require further evaluation in an adequately powered , placebo-controlled , r and omized phase III clinical trial OBJECTIVE To evaluate the effect of soy isoflavones and melatonin in relieving menopausal symptoms . METHODS Double-blind , multicenter , r and omized trial performed according to a 2 x 2 factorial design . Treatment groups : ( 1 ) soy isoflavones+melatonin ; ( 2 ) soy isoflavones alone ; ( 3 ) melatonin alone ; ( 4 ) placebo . 80 mg of soy isoflavones , 3 mg of pure melatonin or placebo were supplemented to participants for 3 months . Severity of menopausal symptoms was recorded at baseline and after 3 months using the Greene Climacteric Scale . RESULTS 388 consecutive women were screened : not eligible 98 , refused informed consent 28 . R and omized 262 and analyzed 232 ; twelve women withdrew because of adverse events . Median percent differences between basal and final scores were 39 % in the isoflavones + melatonin group , 38 % in the isoflavones alone group , 26 % in the melatonin alone group and 38 % in the placebo group . Placebo response was much higher than planned , making it meaningless to perform any statistical test . With regard to somatic and vasomotor symptoms , outcome was similar among the four groups , whereas improvement of psychological symptoms was higher in the isoflavones+melatonin group than in the other three . CONCLUSIONS Present data do not show any advantage of isoflavones or melatonin over placebo for the relief of menopausal symptoms . However , the effect in psychological symptoms in the isoflavones + melatonin group should be further investigated OBJECTIVE This study was design ed to evaluate the effects of equol and resveratrol supplementation on health-related quality of life ( HRQoL ) in otherwise healthy menopausal women with hot flashes , anxiety and depressive symptoms . METHODS Sixty recently menopausal women aged 50 - 55 years were r and omized in a 12-week , placebo-controlled trial to receive 200 mg of fermented soy containing 10 mg of equol and 25 mg of resveratrol ( 1 tablet/day ) . The primary outcome was the change in score on the Menopause Rating Scale ( MRS ) , used to evaluate the severity of age-/menopause-related complaints . Additional outcome measures included the subject-reported score on the Hamilton Rating Scale for Depression ( HAM-D ) and Nottingham Health Profile ( NHP ) , which was used specifically to assess sleep quality . RESULTS The symptoms assessed by the MRS improved during treatment in the active group . Comparison between placebo and treatment groups revealed statistically significant improvement in particular for dryness of vagina ( -85.7 % ) ( p<0.001 ) , heart discomfort ( -78.8 % ; p<0.001 ) and sexual problems ( -73.3 % ; p<0.001 ) . On the HAM-D significant improvements at week 12 were seen in work and activities ( -94.1 % ) ( p<0.001 ) . Subjects treated with equol and resveratrol also had significant differences in the sleep domain of the NHP ( p<0.001 ) . CONCLUSION These findings provide evidence that 12 weeks of dietary supplementation with equol and resveratrol may improve menopause-related quality of life in healthy women Objective : Various non-hormonal agents have been used for the treatment of hot flashes in women with menopause . Some studies have reported that gabapentin appears to be an effective and well-tolerated treatment modality . The aim of this study was to evaluate whether the treatment with gabapentin is effective in reducing hot flash frequency and severity and also to compare gabapentin 100 mg/day , 300 mg/day and conjugated estrogen in this regards . Methods : In this comparative clinical trial , 100 post-menopausal women attending outpatient clinics of Isfahan University hospitals were included from April 2008 to February 2009 . Participants r and omly received gabapentin 300 mg/day , gabapentin 100 mg/day , or conjugated estrogen 0.625 mg/day for 12 weeks . Frequency and severity of hot flashes and adverse effects were compared among the three groups . Findings : From all , 16 participants dropped out . There were no significant differences among the groups before intervention in terms of age , body mass index and baseline hot flash frequency and severity . Hot flash diaries were used to record the frequency and severity of hot flashes . After the treatment period , there was a significant decrease in both severity and frequency of hot flashes in all three groups . Post-hoc analyses showed that the frequency and severity of hot flashes were significantly lower in those who received gabapentin 300 mg/day or estrogen 0.625 mg/day compared to those who received gabapentin 100 mg/day . There was not statistically significant difference between those who received gabapentin 300 mg/day and those who received estrogen . Very few adverse effects , mostly gastrointestinal discomfort were observed in both gabapentin groups ( 8 % ) . Conclusion : Gabapentin 300 mg/day could be useful to relieve hot flashes in women for whom hormone therapy is not suitable or when hot flashes do not respond to other therapies . Further research es are needed to determine the efficacy of gabapentin use for longer periods or at higher doses OBJECTIVE To evaluate the effects of a defined formula of Chinese medicinal herbs ( CMH ) on menopausal symptoms . DESIGN A double-blind r and omised placebo-controlled trial . METHODS Between August 1998 and April 1999 , 55 postmenopausal Australian women recruited from an urban population completed 12 weeks of intervention with either a defined formula of CMH ( n = 28 ) or placebo ( n = 27 ) taken twice daily as a beverage . MAIN OUTCOME MEASURES The primary end-point was change in frequency of vasomotor events ( hot flushes and night sweats ) . The secondary end-points were changes in score for the domains measured in the Menopause Specific Quality of Life ( MENQOL ) Question naire . RESULTS There was a reduction in average weekly frequency of vasomotor events with CMH ( -15 % ; 95 % CI , -31 % to + 1 % ) and with placebo ( -31 % ; 95 % CI , -42 % to -21 % ) . The difference between groups favoured the use of placebo ; however , this was not significant ( P=0.09 ) . Although significant reductions in scores for the various domains of the MENQOL Question naire were observed for both CMH and placebo , there were no significant differences between the two treatment groups for any domain . There was evidence for effect modification by previous use of natural therapies for the vasomotor , physical and sexual domains of the MENQOL Question naire : women with no prior use of natural therapies for their menopausal symptoms responded to therapy , whereas prior users did not . CONCLUSIONS The defined formula of CMH was no more effective than placebo in reducing vasomotor episodes in Australian postmenopausal women , or in improving any of the four symptom domains in the MENQOL Question naire . Three of the MENQOL Question naire domains were modified by prior use of natural therapies . This finding has implication s for future studies BACKGROUND This study evaluates the effect of acupuncture on hot flashes and disturbed night sleep in patients treated for breast cancer . The effect of acupuncture was tested against a sham-acupuncture group and a no-treatment control group . Plasma estradiol was measured to rule out this as cause of effect . Side effects of the treatment were registered . METHODS We r and omized 94 women into the study : 31 had acupuncture , 29 had sham acupuncture and 34 had no treatment . FINDINGS In the acupuncture group , 16 patients ( 52 % ) experienced a significant effect on hot flashes compared with seven patients ( 24 % ) in the sham group ( p < 0.05 ) . The effect came after the second acupuncture session and lasted for at least 12 weeks after last treatment . A statistically significant positive effect was seen on sleep in the acupuncture group compared with the sham-acupuncture and no-treatment groups . The effect was not correlated with increased levels of plasma estradiol . No side effects of acupuncture were registered . INTERPRETATION We find that acupuncture significantly relieves hot flashes and sleep disturbances and is a good and safe treatment in women treated for breast cancer Objective . To compare the efficacy of two sequential 17β-estradiol (17β-E2)/trimegestone ( TMG ) combinations with the sequential estradiol valerate (E2V)/norethisterone ( NET ) regimen in relieving climacteric symptoms . Study design . This was a double-blind , r and omized , multicenter study conducted among 1218 Caucasian ( 99 % ) postmenopausal women with an intact uterus in seven European countries and Israel , over 13 cycles ( each of 28 days ) . Study duration was extended further for 13 cycles , with 531 women receiving treatment for up to 26 cycles . Treatments consisted of 1 mg 17β-E2 on days 1–14 and 1 mg 17β-E2/0.125 mg TMG or 0.25 mg TMG on days 15–28 , and 1 mg E2V on days 1–16 and 1 mg E2V/1 mg NET on days 17–28 . Results . Rapid and significant reductions in the mean daily number and severity of hot flushes and in the mean daily number of nocturnal sweats were established in most women with 1 mg 17β-E2/0.25 mg TMG and E2V/NET . These treatments also induced a significant improvement in the quality -of-life assessment s. Conclusion . The 1 mg 17β-E2/0.25 mg TMG regimen provides rapid and effective relief of menopausal symptoms , with a reduction in the number of hot flushes ‘ at least as good as ’ that of the E2V/NET comparator Objective : The aim of this study was to evaluate the safety and efficacy of black cohosh and red clover compared with placebo for the relief of menopausal vasomotor symptoms . Methods : This study was a r and omized , four-arm , double-blind clinical trial of st and ardized black cohosh , red clover , placebo , and 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate ( CEE/MPA ; n = 89 ) . Primary outcome measures were reduction in vasomotor symptoms ( hot flashes and night sweats ) by black cohosh and red clover compared with placebo ; secondary outcomes included safety evaluation , reduction of somatic symptoms , relief of sexual dysfunction , and overall improvement in quality of life . Results : Reductions in number of vasomotor symptoms after a 12-month intervention were as follows : black cohosh ( 34 % ) , red clover ( 57 % ) , placebo ( 63 % ) , and CEE/MPA ( 94 % ) , with only CEE/MPA differing significantly from placebo . Black cohosh and red clover did not significantly reduce the frequency of vasomotor symptoms as compared with placebo . Secondary measures indicated that both botanicals were safe as administered . In general , there were no improvements in other menopausal symptoms . Conclusions : Compared with placebo , black cohosh and red clover did not reduce the number of vasomotor symptoms . Safety monitoring indicated that chemically and biologically st and ardized extracts of black cohosh and red clover were safe during daily administration for 12 months Objective : To compare the effectiveness and tolerability of gabapentin with placebo for the treatment of hot flashes in women who enter menopause naturally . Design : A r and omized , double-blind , placebo-controlled trial was conducted across the greater Toronto area between March 2004 and April 2006 in the community and primary care setting s. Eligible participants were 200 women in natural menopause , aged 45 to 65 years , having at least 14 hot flashes per week . Study participants were r and omized to receive gabapentin 300 mg oral capsules or placebo three times daily for 4 weeks . The primary outcome measure was the mean percentage change from baseline to week 4 in daily hot flash score , determined from participant diaries . Secondary outcome measures included changes in weekly mean hot flash scores and frequencies , quality of life , and adverse events . Results : Of the 197 participants , 193 ( 98 % ) completed the study . Analysis was by intention to treat . Hot flash scores decreased by 51 % ( 95 % CI : 43%-58 % ) in the gabapentin group , compared with 26 % ( 95 % CI : 18%-35 % ) on placebo , from baseline to week 4 . This twofold improvement was statistically significant ( P < 0.001 ) . The Menopause-Specific Quality -of-Life vasomotor score decreased by 1.7 ( 95 % CI : 1.3 - 2.1 ; P < 0.001 ) in the gabapentin group . These women reported greater dizziness ( 18 % ) , unsteadiness ( 14 % ) , and drowsiness ( 12 % ) at week 1 compared with those taking placebo ; however , these symptoms improved by week 2 and returned to baseline levels by week 4 . Conclusions : Gabapentin at 900 mg/day is an effective and well-tolerated treatment for hot flashes PURPOSE Hot flashes can be a prominent problem in women with a history of breast cancer . Given concerns regarding the use of hormonal therapies in such patients , other nonhormonal means for treating hot flashes are required . Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes , the present trial was developed . PATIENTS AND METHODS This trial used a double-blinded , r and omized , two-period ( 4 weeks per period ) , cross-over methodology to study the efficacy of fluoxetine ( 20 mg/d ) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen ( because of breast cancer risk ) . Eligible patients had to have reported that they averaged at least 14 hot flashes per week ; they could have received tamoxifen or raloxifene as long as they were on a stable dose . The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score , analyzed by a classic sums and differences cross-over analysis . RESULTS Eighty-one r and omized women began protocol therapy . By the end of the first treatment period , hot flash scores ( frequency x average severity ) decreased 50 % in the fluoxetine arm versus 36 % in the placebo arm . Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo ( P = .02 ) . The results were not adjusted for potential confounding influences , including age and tamoxifen use . The fluoxetine was well tolerated . CONCLUSION This dose of fluoxetine result ed in a modest improvement in hot flashes BACKGROUND Hot flashes can be troublesome , especially when hormonal therapy is contraindicated . Preliminary data have suggested that newer antidepressants , such as venlafaxine , can diminish hot flashes . We undertook a double-blind , placebo-controlled , r and omised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer . METHODS Participants were assigned placebo ( n=56 ) or venlafaxine 37.5 mg daily ( n=56 ) , 75 mg daily ( n=55 ) , or 150 mg daily ( n=54 ) . After a baseline assessment week , patients took the study medication for 4 weeks . All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups . Patients completed daily hot-flash question naire diaries . The primary endpoint was average daily hot-flash activity ( number of flashes and a score combining number and severity ) . Analyses were based on the women who provided data throughout the baseline and study weeks . FINDINGS 191 patients had evaluable data for the whole study period ( 50 placebo , 49 venlafaxine 37.5 mg , 43 venlafaxine 75 mg , 49 venlafaxine 150 mg ) . After week 4 of treatment , median hot flash scores were reduced from baseline by 27 % ( 95 % CI 11 - 34 ) , 37 % ( 26 - 54 ) , 61 % ( 50 - 68 ) , and 61 % ( 48 - 75 ) in the four groups . Frequencies of some side-effects ( mouth dryness , decreased appetite , nausea , and constipation ) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group . INTERPRETATION Venlafaxine is an effective non-hormonal treatment for hot flashes , though the efficacy must be balanced against the drug 's side-effects . Confirmation of the results of this 4-week study awaits the completion of three ongoing r and omised studies to assess the effects of other related antidepressants for the treatment of hot flashes CONTEXT Concerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have result ed in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes . OBJECTIVE To determine the efficacy and tolerability of 10 to 20 mg/d escitalopram , a selective serotonin reuptake inhibitor , in alleviating the frequency , severity , and bother of menopausal hot flashes . DESIGN , SETTING , AND PATIENTS A multicenter , 8-week , r and omized , double-blind , placebo-controlled , parallel group trial that enrolled 205 women ( 95 African American ; 102 white ; 8 other ) between July 2009 and June 2010 . INTERVENTION Women received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks . MAIN OUTCOME MEASURES Primary outcomes were the frequency and severity of hot flashes assessed by prospect i ve daily diaries at weeks 4 and 8 . Secondary outcomes were hot flash bother , recorded on daily diaries , and clinical improvement ( defined as hot flash frequency ≥50 % decrease from baseline ) . RESULTS Mean ( SD ) daily hot flash frequency was 9.78 ( 5.60 ) at baseline . In a modified intent-to-treat analysis that included all r and omized participants who provided hot flash diary data , the mean difference in hot flash frequency reduction was 1.41 ( 95 % CI , 0.13 - 2.69 ) fewer hot flashes per day at week 8 among women taking escitalopram ( P < .001 ) , with mean reductions of 4.60 ( 95 % CI , 3.74 - 5.47 ) and 3.20 ( 95 % CI , 2.24 - 4.15 ) hot flashes per day in the escitalopram and placebo groups , respectively . Fifty-five percent of women in the escitalopram group vs 36 % in the placebo group reported a decrease of at least 50 % in hot flash frequency ( P = .009 ) at the 8-week follow-up . Reductions in hot flash severity scores were significantly greater in the escitalopram group ( -0.52 ; 95 % CI , -0.64 to -0.40 vs -0.30 ; 95 % CI , -0.42 to -0.17 for placebo ; P < .001 ) . Race did not significantly modify the treatment effect ( P = .62 ) . Overall discontinuation due to adverse events was 4 % ( 7 in the active group , 2 in the placebo group ) . Three weeks after treatment ended , women in the escitalopram group reported a mean 1.59 ( 95 % CI , 0.55 - 2.63 ; P = .02 ) more hot flashes per day than women in the placebo group . CONCLUSION Among healthy women , the use of escitalopram ( 10 - 20 mg/d ) compared with placebo result ed in fewer and less severe menopausal hot flashes at 8 weeks of follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00894543 Objective To assess the clinical ly optimal tibolone dose for the relief of climacteric complaints PURPOSE Vasomotor symptoms are common adverse effects of antiestrogen hormone treatment in conventional breast cancer care . Hormone replacement therapy is contraindicated in patients with breast cancer . Venlafaxine ( Effexor ) , the therapy of choice for these symptoms , has numerous adverse effects . Recent studies suggest acupuncture may be effective in reducing vasomotor symptoms in menopausal women . This r and omized controlled trial tested whether acupuncture reduces vasomotor symptoms and produces fewer adverse effects than venlafaxine . PATIENTS AND METHODS Fifty patients were r and omly assigned to receive 12 weeks of acupuncture ( n = 25 ) or venlafaxine ( n = 25 ) treatment . Health outcomes were measured for up to 1 year post-treatment . RESULTS Both groups exhibited significant decreases in hot flashes , depressive symptoms , and other quality -of-life symptoms , including significant improvements in mental health from pre- to post-treatment . These changes were similar in both groups , indicating that acupuncture was as effective as venlafaxine . By 2 weeks post-treatment , the venlafaxine group experienced significant increases in hot flashes , whereas hot flashes in the acupuncture group remained at low levels . The venlafaxine group experienced 18 incidences of adverse effects ( eg , nausea , dry mouth , dizziness , anxiety ) , whereas the acupuncture group experienced no negative adverse effects . Acupuncture had the additional benefit of increased sex drive in some women , and most reported an improvement in their energy , clarity of thought , and sense of well-being . CONCLUSION Acupuncture appears to be equivalent to drug therapy in these patients . It is a safe , effective and durable treatment for vasomotor symptoms secondary to long-term antiestrogen hormone use in patients with breast cancer Abstract Objectives To evaluate the effectiveness of black cohosh extract 40 mg/day for relieving moderate to severe menopausal symptoms and improving quality of life in Thai women . Methods A r and omized , double-blind , placebo-controlled clinical trial was conducted in a menopause clinic of a tertiary-care university hospital during 2011–2013 . Participants were peri- or postmenopausal Thai women aged at least 40 years , who have moderate to severe menopausal symptoms evaluated using the Kupperman index ( KI ) . Outcome measures included KI , frequency of hot flushes , Menopause-Specific Quality of Life ( MENQOL ) score , participants ’ global satisfaction and safety outcomes . Results There were 54 participants assigned to treatment ( black cohosh extract 40 mg/day , n = 27 ) or placebo group ( n = 27 ) . Both the treatment and placebo groups had comparable baseline KI scores ( 33.9 ± 7.9 vs. 31.3 ± 6.8 ) , frequency of hot flushes ( 3.1 ± 2.0 vs. 2.8 ± 2.1 ) , and MENQOL scores , all of which improved with time . Neither the improvements nor the global satisfaction were significantly different between the two groups ; but the proportion of participants with moderate to severe symptoms seemed to be lower in the treatment group than in the placebo group ( 40 % vs. 60 % , p = 0.174 ) . There was no serious adverse event or significant change in liver function tests . Conclusions A black cohosh extract of 40 mg/day is not superior to a placebo for relieving moderate to severe menopausal symptoms or improving quality -of-life scores in Thai women Objective : The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women . Design : This was a r and omized , double-blind , placebo-controlled trial of menopausal women , aged 38 to 60 years , who experienced 4 to 14 hot flashes per day . After a 1-week run-in period , a total of 190 menopausal women were r and omized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks . The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary . The secondary outcomes included changes in quality of life and hormonal profiles . Results : A total of 147 women ( 77 % ) completed the study . It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally . At 8 weeks hot flash frequency was reduced by 43 % in the 40-mg DRI group and by 41 % in the 60-mg DRI group , compared with 32 % in the placebo group ( P = not significant vs placebo ) . The corresponding numbers for 12 weeks were 52 % , 51 % , and 39 % , respectively ( P = 0.07 and 0.09 vs placebo ) . When comparing the two treatment groups with the placebo group , there were significant reductions in mean daily hot flash frequency . The supplement ( either 40 or 60 mg ) reduced hot flash frequency by 43 % at 8 weeks ( P = 0.1 ) and 52 % at 12 weeks ( P = 0.048 ) but did not cause any significant changes in endogenous sex hormones or thyroid hormones . Menopausal quality of life improved in all three groups , although there were no statistically significant differences between groups . Conclusions : DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes OBJECTIVE The aim of this study was to demonstrate clinical equivalence between a novel intranasal estradiol formulation and a reference oral drug . STUDY DESIGN In this multinational , double-blind , parallel-group study 659 postmenopausal women with moderate to severe postmenopausal symptoms were r and omly assigned to receive either 300 microg/d intranasal 17beta-estradiol ( S21400 ) or 2 mg/d oral micronized estradiol , plus the appropriate placebo , for 24 weeks . All patients also received 10 mg/d dydrogesterone for 14 days per 28-day cycle . Adjustment of intranasal dosage was permitted from week 14 on . The primary efficacy criterion was the Kupperman index at week 14 , with a predefined limit of equivalence of 4 . RESULTS Kupperman index scores improved similarly in the 2 groups , from 28.4 + /- 6.2 to 10.0 + /- 8.6 ( mean + /- SD ) for S21400 and from 28.1 + /- 6.0 to 8.9 + /- 8.0 for oral therapy , with a difference between groups at week 14 of 1.1 + /- 0.6 ( 90 % confidence interval , 0 . 0 to 2.2 ) . This was below the predefined equivalence limit of + 4 for statistical noninferiority ( P < .001 ) . The daily number and intensity of hot flushes decreased similarly in the two treatment groups . Withdrawal bleeding was 20 % less frequent with intranasal therapy ( 90 % confidence interval , 12.5 to 27.6 ) . Severe mastalgia was less frequent in the S21400 group ( 1.0 % ) than in the group with oral therapy ( 5.2 % ; P < .01 ) . Triglyceride and angiotensinogen levels increased significantly with oral therapy but not with S21400 . The same number of patients required dose adaptation in the 2 groups ( approximately 20 % ) . CONCLUSION Intranasal administration of 300 microg/d estradiol was at least as effective as oral administration of 2 mg/d estradiol in alleviating postmenopausal symptoms , with less frequent mastalgia and uterine bleeding and without the metabolic consequences of the first-pass effect Objective : Assess effects of once-daily , extended-release oxybutynin chloride on frequency and severity of vasomotor symptoms in healthy , postmenopausal symptomatic women . Methods : A 12-week , multicenter , double-blind , placebo-controlled , phase 2 clinical trial r and omized naturally postmenopausal women experiencing at least seven moderate-to-severe vasomotor symptoms daily to oxybutynin 15 mg once daily ( n = 73 ) or placebo ( n = 75 ) . Co- primary outcomes were the change from baseline to week 12 in the frequency and severity of moderate-to-severe vasomotor symptoms . Results : Significant reductions in both frequency and severity of moderate-to-severe vasomotor symptoms in women who received oxybutynin compared with placebo were observed at all weeks of treatment ( P ⩽ 0.007 , all time points ) through week 12 . Mean changes in frequency in the oxybutynin and placebo groups were −9.48 and −4.69 episodes/d , respectively , at week 12 . Mean changes in severity ( scale 0 - 3 ) in the oxybutynin and placebo groups were −1.27 and −0.30 , respectively , at week 12 . At the end of treatment , 73 % of women in the oxybutynin group and 26.1 % in the placebo group rated symptom improvement “ much better ” ( P ⩽ 0.001 ) . Women treated with oxybutynin showed significant improvement in sleep quality , sleep disturbance , and the global sleep index on the Pittsburgh Sleep Quality Index ( P ⩽ 0.023 ) . Dry mouth was reported by 52.1 % of participants given oxybutynin and 5.3 % of participants given placebo , leading to discontinuation of oxybutynin in 6.8 % of participants . Conclusions : Oxybutynin is an effective , nonhormonal therapy for moderate-to-severe vasomotor symptoms in postmenopausal women OBJECTIVE : To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol ( E2 ) gel for relief of menopausal symptoms in a population of postmenopausal women . METHODS : This study was a r and omized , double-blind , placebo-controlled , multicenter , parallel-group study . Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d ( n=136 ) , 1.7 g/d ( n=142 ) , or 2.6 g/d ( n=69 ) E2 gel or placebo gel ( n=137 ) topically for 12 weeks . The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined . RESULTS : With increasing E2 doses , mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3–5 , E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day ( P<.001 ) and reduced the severity score ( P<.01 ) . The numbers needed to treat for benefit for an 80 % and 100 % decrease in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group . At week 12 , vaginal pH was more acidic and vaginal maturation index more mature compared with placebo ( P<.001 ) . The lowest dose improved most bothersome vulvovaginal atrophy symptoms ( P<.05 ) . Estradiol gel was well tolerated at the site of application and produced no unexpected adverse effects . The 0.87 g/d dose produced fewest adverse events . CONCLUSION : The 0.87 g/d dose of this new transdermal E2 gel , which delivers an estimated 0.0125 mg E2 daily , delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00391417 LEVEL OF EVIDENCE : Objective : To evaluate the effectiveness of a selective serotonin reuptake inhibitor ( SSRI ) ( sertraline ) in decreasing hot flashes in a general population of women . Design : A double-blind , placebo-controlled , crossover trial was conducted in a southwestern urban setting . A total of 102 women aged 40 to 65 who were experiencing hot flashes and not taking any hormone therapy were recruited . After 1 week of baseline hot flash data collection , study participants were r and omized to receive placebo or active drug ( sertraline 50 mg ) for 4 weeks . This intervention was followed by a 1-week washout and cross over to the opposite treatment for 4 weeks . The number and severity of hot flashes were measured . Results : One hundred two women were enrolled in the study . Five dropped out before providing baseline data . Of the 97 remaining , 52 were r and omized to active drug first and 45 to placebo first . Ten dropped out of the study before completing all 10 weeks , leaving 46 in the active drug-first arm and 41 in the placebo-first arm . At baseline , the mean number of hot flashes reported was 45.6 per week ( SD = 29.6 ) , ranging from 2 to 148 . During the sertraline phase of the study , women experienced five fewer hot flashes per week than they did on the placebo ( P = 0.002 ) . The severity of hot flashes was not significantly different ; however , the hot flash score ( number × average severity ) was significantly improved during the sertraline phase . Conclusion : Sertraline reduced the number of hot flashes and improved the hot flash score relative to placebo and may be an acceptable alternative treatment for women experiencing hot flashes Objective : To confirm the efficacy and safety of pulsed estrogen therapy , a transient daily hormone exposure , for climacteric symptoms in highly symptomatic postmenopausal women . Patients and methods : In this multicenter , double-blind , parallel-group study , early postmenopausal women with at least seven moderate to severe vasomotor symptoms per day were r and omized to receive intranasal estradiol , 150 or 300 μg/day , or placebo , for 12 weeks . The primary outcome measure was the mean daily number of moderate to severe vasomotor symptoms , as recorded in patient diaries . Results : A total of 165 patients were r and omized . The mean daily number of moderate to severe vasomotor symptoms decreased significantly more ( p < 0.001 ) in the 150-μg/day ( –7.86 ) and 300-μg/day ( –9.39 ) groups than in the placebo group ( –5.22 ) . The decrease reached significance more rapidly with the 300-μg/day dose ( from week 2 ) than with the 150-μg/day dose ( from week 8) . The rate of emergent adverse events with both doses was similar to that with placebo . Conclusions : Pulsed estrogen therapy , achieved by intranasal estradiol 150 μg/day and 300 μg/day , significantly reduced the incidence of moderate to severe vasomotor symptoms , compared with placebo . The 300-μg/day dose demonstrated a greater and more rapid therapeutic effect , with no clinical ly significant difference in tolerability , compared with the 150-μg/day dose , and therefore offers the best efficacy/safety ratio when initiating treatment with intranasal estradiol OBJECTIVE To evaluate the efficacy of synthetic genistein for reducing the frequency and severity of hot flushes . STUDY DESIGN A 12 week r and omized double-blind , placebo-controlled study in which 84 postmenopausal women received placebo or a single 30 mg dose of synthetic genistein . Outcome measures primary : percentage change in the number of daily hot flushes from pre-treatment to week 12 . Secondary : duration and severity of daily hot flushes , Greene Climacteric Scale score , serum follicle stimulating hormone ( FSH ) , 17β-estradiol and endometrial thickness . RESULTS Genistein supplemented subjects completing at least 4 weeks on trial ( n=40 ) demonstrated a 51 % reduction ( 9.4 - 4.7/day ) in the number of hot flushes by week 12 compared to a 27 % reduction in the placebo group ( 9.9 - 7.1/day ) ( p=0.026 ) . Subjects in the genistein group also reported significantly fewer hot flushes per day ( p=0.010 ) and a decrease in total duration of hot flushes per day ( p=0.009 ) at week 12 versus placebo . Subjects on genistein ( n=32 ) completing 12 weeks on trial demonstrated a 51 % reduction ( 9.7 - 4.7/day ) in the number of hot flushes by week 12 ( p=0.049 ) compared to 30 % reduction in the placebo group ( 9.8 - 7.0/day ) and had fewer hot flushes per day and a decrease in total duration of hot flushes per day at week 12 compared to placebo ( p=0.020 and p=0.017 , respectively ) . There were no differences between groups in Greene Climacteric Scale , FSH , 17β-estradiol , endometrial thickness or adverse events . CONCLUSIONS The current study provides the first evidence that a single daily dose of 30 mg of synthetic genistein reduces hot flush frequency and duration OBJECTIVE To evaluate whether treatment with the anticonvulsant gabapentin may be effective in reducing hot flash frequency and severity . METHODS A r and omized , double-blind , placebo-controlled trial was conducted in 59 postmenopausal women with seven or more hot flashes per day examining the effects of gabapentin 900 mg per day on hot flash frequency after 12 weeks of treatment . Subsequently , study patients were enrolled in a 5-week , open-label treatment phase , during which patients could increase the dose of gabapentin to 2700 mg per day , if needed . RESULTS After 12 weeks of double-blind treatment , intention-to-treat analysis showed that gabapentin 900 mg per day was associated with a 45 % reduction in hot flash frequency and a 54 % reduction in hot flash composite score ( frequency and severity combined into one score ) from baseline , compared with 29 % ( P = .02 ) and 31 % ( P = .01 ) reductions , respectively , for placebo . Four patients ( 13 % ) in the gabapentin group and one ( 3 % ) in the placebo group withdrew from the double-blind study because of adverse events . Fifteen patients ( 50.0 % ) in the gabapentin group reported at least one adverse event , compared with eight patients ( 27.6 % ) in the placebo group . Higher , open-label gabapentin dosing was associated with 54 % and 67 % reductions in hot flash frequency and composite score from baseline , respectively . CONCLUSION Gabapentin is effective in reducing hot flash frequency and severity in postmenopausal women Objective : To compare a novel vaginal ring releasing estradiol acetate ( Menoring ® ; Galen Holdings ) with oral estradiol for relief of moderate to severe vasomotor symptoms in healthy postmenopausal women . Design : This was a prospect i ve , double-blind , multicenter , r and omized , parallel-group study . Method : Women ( n = 159 ) aged < 65 years experiencing ≥ 20 hot flushes/night sweats per week received either a vaginal ring releasing estradiol acetate at a rate equivalent to 50 μg/day estradiol plus placebo tablets or oral estradiol 1 mg/day plus a placebo vaginal ring for 24 weeks . For patients with inadequate control of symptoms , the dosage was doubled at 12 weeks . A 24-week , open-label extension of the vaginal ring treatment followed double-blind treatment . Results : The frequency of hot flushes/night sweats was significantly reduced ( p < 0.001 ) in both groups at 12 and 24 weeks from baseline , by 84 % and 94 % for the vaginal ring group and by 73 % and 83 % for the oral group , respectively . The mean intensity of urogenital symptoms decreased from screening to the end of treatment in both groups . The incidence of adverse events was similar for both groups . No clinical ly relevant local effects of the vaginal ring were observed . Conclusions : The vaginal ring relieved both systemic and urogenital symptoms and was well tolerated and accepted . Overall , the efficacy , safety and acceptability of the vaginal ring were comparable with those of oral estradiol therapy Objective : First , to identify treatment satisfaction thresholds for interpreting treatment-related changes in vasomotor symptoms , and , second , to determine the doses of desvenlafaxine ( DVS ) ( administered as desvenlafaxine succinate ) that effectively provide relief of vasomotor symptoms considered important by menopausal women . Design : Efficacy and treatment satisfaction were assessed in 620 postmenopausal women with moderate to severe vasomotor symptoms participating in a double-blind , placebo-controlled trial and r and omly assigned to placebo or 50 , 100 , 150 , or 200 mg DVS . Number and severity of hot flushes and number of nighttime awakenings were recorded in daily diaries for 12 weeks of treatment . At week 12 , responses to the Menopause Symptoms Treatment Satisfaction Question naire were compared with efficacy results . Results : Greater percentages of participants in the DVS groups reported being " satisfied " or " extremely satisfied " with daytime and nighttime control of hot flushes compared with placebo . The treatment satisfaction threshold , defined as the difference between the average reduction in vasomotor symptoms for women who were " neutral " versus " satisfied , " was 1.64 for moderate to severe hot flushes and 0.42 for nighttime awakenings . Statistically significant reductions with 100 , 150 , and 200 mg DVS exceeded treatment satisfaction threshold results for at least one of these thresholds , and results with 100 mg DVS compared with placebo exceeded both treatment satisfaction thresholds . Conclusions : Among menopausal women with moderate to severe vasomotor symptoms , the treatment satisfaction thresholds that were meaningful to participants were 1.64 fewer moderate to severe hot flushes per day and 0.42 fewer nighttime awakenings per night . A dose of 100 mg DVS met both of these important vasomotor symptom change thresholds Objective To investigate the efficacy of dietary soy proteins containing differing amounts of isoflavones on the number and severity of vasomotor symptoms ( hot flashes and night sweats ) in peri- and postmenopausal women . Design A double-masked , r and omized , controlled , clinical trial was conducted . A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were r and omized into one of three groups . In all groups , participants consumed a daily supplement containing 25 g of soy protein and were r and omly assigned to one of three groups : ( a ) isoflavone extracted soy protein ( control ) , ( b ) soy protein with a medium dose of isoflavones ( 42 mg/day ) , or ( c ) soy protein with a higher dose of isoflavones ( 58 mg/day ) . The primary outcome measure in this trial was change in reported vasomotor symptoms . Results A reduction in the number and severity of vasomotor symptoms was observed in all three treatment groups . No significant differences in the number and severity of vasomotor symptoms were observed among the high isoflavone , middle isoflavone , or control groups . The lack of a between-treatment group effect was observed even after stratified by number of baseline symptoms and use of traditional hormone replacement therapy . Conclusions These data suggest that soy protein containing 42 or 58 mg of isoflavones is no more effective than isoflavone-extracted soy protein for improving the number and severity of vasomotor symptoms in peri- and postmenopausal women ABSTRACT Objectives To determine the efficacy and safety of low-dose maintenance therapy with transdermal estradiol ( E2 ) gel in Japanese women with climacteric disorder and estrogen deficiency symptoms . Methods Women ( n = 209 ) aged 37–59 years who had climacteric disorder or estrogen deficiency symptoms received a st and ard dose of transdermal E2 gel ( 1.8 g/day , containing E2 1.08 mg/day ) for 8 weeks as induction treatment . A total of 177 women in whom the number of daily hot flushes had decreased to less than one-third of the baseline value ( marked improvement ) at week 8 were double-blindly r and omized to receive low-dose E2 ( n = 88 , 0.9 g/day , containing E2 0.54 mg/day ) or E2-free placebo ( n = 89 ) for 16 weeks . Results Improvement rates in the number of daily hot flushes at the final evaluation ( primary endpoint ) in the low-dose E2 group ( marked 90.8 % , moderate 6.9 % , mild 1.1 % , no change 1.1 % , worsening 0 % ) were significantly greater than in the placebo group ( marked 77.0 % , moderate 10.3 % , mild 4.6 % , no change 2.3 % , worsening 5.7 % ) ( p = 0.0097 ) , showing an inhibitive effect on the flare-up of climacteric symptoms . The incidence of treatment-related adverse events in the low-dose group ( 21.6 % ) was similar to that in the placebo ( 22.5 % ) but was lower than that in the st and ard-dose treatment ( 32.5 % ) . Conclusions Low-dose maintenance therapy that was half the st and ard dose of transdermal E2 gel ( 0.9 g/day ) applied to women who had achieved marked improvement in the number of hot flushes at the st and ard dose ( 1.8 g/day ) was demonstrated to be effective ( inhibition of recurrence ) and safe for the treatment of climacteric disorder and estrogen deficiency symptoms Objective The efficacy and safety of low-dose paroxetine 7.5 mg for the treatment of menopausal vasomotor symptoms were evaluated in two multicenter , double-blind , placebo-controlled , phase 3 studies of 12 and 24 weeks ’ duration . Methods Postmenopausal women were r and omly assigned 1:1 to receive paroxetine 7.5 mg or placebo once daily . The four primary efficacy endpoints included mean changes in the frequency and severity of moderate to severe vasomotor symptoms on weeks 4 and 12 ; an additional endpoint was persistence of treatment benefit on week 24 . Results Five hundred ninety-one participants were r and omly assigned to treatment with paroxetine 7.5 mg , and 593 participants were r and omly assigned to treatment with placebo . All primary endpoints were met in the 24-week study ; three of four primary endpoints were met in the 12-week study . In both studies , paroxetine 7.5 mg significantly reduced the mean weekly vasomotor symptom frequency compared with placebo on week 4 ( P < 0.0001 for both studies ) and week 12 ( P = 0.0090 , 12-wk study ; P = 0.0001 , 24-wk study ) . Mean weekly reduction in vasomotor symptom severity was significantly greater for paroxetine 7.5 mg than for placebo on week 4 ( P = 0.0048 ) in the 12-week study and on week 4 ( P = 0.0452 ) and week 12 ( P = 0.0114 ) in the 24-week study . Persistence of treatment benefit was demonstrated in the 24-week study . Most treatment-emergent adverse events were mild or moderate in severity . No clinical ly significant changes in laboratory values or vital signs were noted , and no short-term discontinuation of symptoms followed treatment cessation . Conclusions Paroxetine 7.5 mg is well-tolerated , is effective in reducing the frequency and severity of menopausal vasomotor symptoms , and demonstrates persistence of treatment benefit through 24 weeks of treatment ABSTRACT BACKGROUND Paced respiration has been internationally recommended for vasomotor symptom management , despite limited empirical evidence . OBJECTIVE To evaluate efficacy of a paced respiration intervention against breathing control and usual care control for vasomotor and other menopausal symptoms . DESIGN A 16-week , 3-group , partially blinded , controlled trial with 2:2:1 r and omization and stratification by group ( breast cancer , no cancer ) , in a Midwestern city and surrounding area . PARTICIPANTS Two hundred and eighteen r and omized women ( 96 breast cancer survivors , 122 menopausal women without cancer ) , recruited through community mailings and registries ( 29 % minority ) . INTERVENTIONS Training , home practice support , and instructions to use the breathing at the time of each hot flash were delivered via compact disc with printed booklet ( paced respiration intervention ) or digital videodisc with printed booklet ( fast shallow breathing control ) . Usual care control received a letter regarding group assignment . MAIN MEASURES Hot flash frequency , severity , and bother ( primary ) ; hot flash interference in daily life , perceived control over hot flashes , and mood and sleep disturbances ( secondary ) . Intervention performance , adherence , and adverse events were assessed . KEY RESULTS There were no significant group differences for primary outcomes at 8-weeks or 16-weeks post-r and omization . Most intervention participants did not achieve 50 % reduction in vasomotor symptoms , despite demonstrated ability to correctly do paced respiration and daily practice . Statistically significant differences in secondary outcomes at 8 and 16 weeks were small , not likely to be clinical ly relevant , and as likely to favor intervention as breathing control . CONCLUSIONS Paced respiration is unlikely to provide clinical benefit for vasomotor or other menopausal symptoms in breast cancer survivors or menopausal women without cancer OBJECTIVE To compare the efficacy of two strengths of an estradiol matrix transdermal delivery system with daily oral doses of conjugated equine estrogens in reducing the frequency of moderate-to-severe hot flushes in postmenopausal women . DESIGN The design of the study provided for the following treatment regimens : an estradiol transdermal delivery system ( Alora 0.05 or 0.1 mg/day ) administered twice weekly or oral doses of conjugated equine estrogens ( CEE 0.625 or 1.25 mg ) administered daily were given to 321 highly symptomatic postmenopausal women for 12 weeks following a r and omized , parallel-group , double-blind , double-dummy design . RESULTS Results indicate no statistically significant differences at any time point in mean frequency or mean percentage reduction in frequency of moderate-to-severe hot flushes between patients given Alora 0.1 mg/day and those receiving CEE 1.25 mg/day . Similarly , no significant differences were observed at any time in mean frequency of moderate-to-severe hot flushes between the Alora 0.05 mg/day and CEE 0.625 mg/day groups , although the group receiving CEE 0.625 mg/day exhibited a statistically greater percentage reduction than the Alora 0.05 mg/day group at weeks 3 , 4 and 8 . By week 12 , these two treatments were statistically indistinguishable . There were no serious or unexpected adverse events with the two transdermal systems and local skin tolerability was excellent . Other estrogenic effects such as restoration of vaginal cytology , breast tenderness and unexpected vaginal bleeding were comparable between transdermal and oral administration groups except for a lower incidence of bleeding in those women receiving the lower dose transdermal regimen Objective The use of estrogen and progesterone to manage vasomotor symptoms ( ie , hot flashes and night sweats ) has declined because of concerns about their risks , and there is an increased interest in alternate , effective , and low-risk treatments . This study reports the results of a r and omized controlled trial of clinical hypnosis for treating vasomotor symptoms among postmenopausal women . Methods This is a r and omized , single-blind , controlled , clinical trial involving 187 postmenopausal women reporting a minimum of seven hot flashes per day ( or at least 50 hot flashes a week ) at baseline between December 2008 and April 2012 . Eligible participants received five weekly sessions of either clinical hypnosis or structured-attention control . Primary outcomes were hot flash frequency ( subjectively and physiologically recorded ) and hot flash score assessed by daily diaries on weeks 2 to 6 and week 12 . Secondary outcomes included measures of hot flash – related daily interference , sleep quality , and treatment satisfaction . Results In a modified intent-to-treat analysis that included all r and omized participants who provided data , reported subjective hot flash frequency from baseline to week 12 showed a mean reduction of 55.82 ( 74.16 % ) hot flashes for the clinical hypnosis intervention versus a mean reduction of 12.89 ( 17.13 % ) hot flashes for controls ( P < 0.001 ; 95 % CI , 36.15 - 49.67 ) . The mean reduction in hot flash score was 18.83 ( 80.32 % ) for the clinical hypnosis intervention as compared with 3.53 ( 15.38 % ) for controls ( P < 0.001 ; 95 % CI , 12.60 - 17.54 ) . At 12-week follow-up , the mean reduction in physiologically monitored hot flashes was 5.92 ( 56.86 % ) for clinical hypnosis and 0.88 ( 9.94 % ) for controls ( P < 0.001 ; 95 % CI , 2.00 - 5.46 ) . Secondary outcomes were significantly improved compared with controls at 12-week follow-up : hot flash – related interference ( P < 0.001 ; 95 % CI , 2.74 - 4.02 ) , sleep quality ( P < 0.001 ; 95 % CI , 3.65 - 5.84 ) , and treatment satisfaction ( P < 0.001 ; 95 % CI , 7.79 - 8.59 ) . Conclusions Compared with structured-attention control , clinical hypnosis results in significant reductions in self-reported and physiologically measured hot flashes and hot flash scores in postmenopausal women Objective : To compare the efficacy and tolerability of a new oral estradiol prodrug , estradiol acetate , with micronized estradiol or conjugated equine estrogens for alleviation of postmenopausal vasomotor and urogenital symptoms . Design : A total of 249 postmenopausal women experiencing seven or more moderate or severe vasomotor symptoms daily for 1 week or 60 or more symptoms in 1 week were r and omized to 0.9 mg of estradiol acetate ( n = 79 ) , 1 mg of micronized estradiol ( n = 85 ) , or 0.625 mg of conjugated equine estrogens therapy ( n = 85 ) . Efficacy endpoints were the change in frequency and severity of vasomotor symptoms from baseline to week 12 , participant-assessed urogenital symptoms , and investigator-assessed signs of vaginal atrophy . Efficacy results were considered equivalent if estradiol acetate was at least 80 % as effective as estradiol and conjugated estrogens . Results : At week 12 , frequency of vasomotor symptoms decreased comparably in all groups , and at weeks 4 and 12 , the decrease in frequency of symptoms was statistically equivalent for estradiol acetate and conjugated estrogens . Severity of vasomotor symptoms also improved comparably for all groups , with least squares mean decreases of 1.05 for estradiol acetate , 1.34 for estradiol , and 1.17 for conjugated estrogens at week 12 . Urogenital symptoms and vaginal signs showed similar improvement in all groups . Overall , the majority of adverse events were mild or moderate and consistent with estrogen therapy . Conclusion : Estradiol acetate 0.9 mg was comparable to 1 mg of estradiol and 0.625 mg of conjugated equine estrogens in reducing the number and severity of vasomotor and urogenital symptoms in postmenopausal women . Oral estradiol acetate was well tolerated To assess the psychometric properties of the Hot Flash Related Daily Interference Scale ( HFRDIS ) , a sample of breast cancer survivors and an age-matched comparison group completed a question naire packet and 2-day prospect i ve hot flash diary at an initial time point and again 6 months later . There were 71 breast cancer survivors and 63 comparators at Time 1 , and 54 survivors and 46 comparators at Time 2 . The HFRDIS was internally consistent , with alphas of 0.96 at times 1 and 2 . Validity was supported through 1 ) correlations with other hot flash variables , 2 ) correlations with measures of affect and mood , 3 ) significant differences between women with hot flashes and those without , and 4 ) demonstrated sensitivity to change over time . The HFRDIS is a psychometrically sound measure for assessing the impact of hot flashes on daily activities and overall quality of life in clinical practice or research protocol Objective : To determine the difference , if any , in the placebo response when both perimenopausal and postmenopausal women are enrolled , compared with postmenopausal women alone , in a study assessing the efficacy of synthetic conjugated estrogen tablets on moderate-to-severe vasomotor symptoms ( MSVS ) . Methods : A total of 120 healthy women ( 72 active ; 48 placebo ) complaining of moderate-to-severe vasomotor symptoms were enrolled in a r and omized , placebo-controlled , double-blind , multicenter clinical trial . In all , 109 patients completed treatment to week 12 . Women were enrolled using minimal inclusion and exclusion criteria , and included perimenopausal women ( n = 34 ; 0 to 6 months since last menses ) as well as menopausal women ( n = 79 ; > 12 months since last menses ) . Results : Changes in MSVS in the intent-to-treat ( ITT ) population showed differences between the active and placebo treatments at weeks 4 ( p < 0.022 ) , 8 ( p < 0.010 ) and 12 ( p < 0.010 ) . At week 12 , the mean percentage reduction in MSVS was 81 % for the active treatment group and 58 % in the placebo treatment group . To examine the placebo response , the ITT population was broken down into groups defined by the time since their last menses . The perimenopausal group ( 0 to 6 months since last menses ) demonstrated a consistently higher placebo response than that of the postmenopausal groups ( > 12 months since last menses ) . Conclusions : Perimenopausal women contributed to a higher placebo response , compared with the rate of response previously reported in clinical studies of estrogen replacement in postmenopausal women . Including perimenopausal women in future vasomotor symptom trials will require study population s of sufficient size to maintain the statistical power to demonstrate a difference between therapeutic response to active or placebo treatment Objective This work aim ed to study the efficacy of group therapy with applied relaxation on vasomotor symptoms and health-related quality of life in postmenopausal women . Methods In this open , r and omized controlled trial , 60 healthy postmenopausal women with at least seven moderate to severe hot flashes per 24 hours were r and omized to either group therapy with applied relaxation ( n = 33 ) or untreated control group ( n = 27 ) for 12 weeks . A follow-up visit was scheduled 3 months after the end of therapy or participation in the control group . Salivary cortisol was measured three times during a 6-month period . Hot flashes were recorded in self-registered diaries , and health-related quality of life was assessed with the Women ’s Health Question naire . Results The number of hot flashes decreased by 5.0 per 24 hours in the applied relaxation group compared with 1.9 in the control group on the 12th week ( P < 0.001 ) and still remained at the same level at the 3-month follow-up ( P < 0.001 ) . Health-related quality of life for vasomotor symptoms , sleep , and memory improved significantly on the 12th week measurement in the applied relaxation group compared with the control group . Salivary cortisol concentration was lowered markedly in the applied relaxation group on a single measurement but was otherwise mainly stable in both groups . Conclusions Applied relaxation can be used to treat vasomotor symptoms in healthy postmenopausal women Two-hundred and fourteen ( 214 ) menopausal women with moderate to severe vasomotor symptoms , aged 40 - 65 years , were r and omised . After a 4-week treatment-free period , each women received a continuous regimen of Menorest 50 twice weekly or Premarin 0.625 mg daily , for 12 weeks . Didrogesterone 10 mg was also given to all women for 12 days of every 28-day cycle . The objectives were to compare the efficacy and safety profiles of Menorest and an oral estrogen . A statistically significant reduction in the mean number of hot flushes occurred in each group compared to baseline with a decrease from 7.1 at baseline to 0.9 at 12 weeks in the Menorest group , and from 6.7 to 0.5 in the oral estrogen group ; there was no statistically significant difference between the two groups ( P = 0.36 ) . With each successive treatment cycle , there was a continuous improvement in the number of hot flushes . The incidence and severity of menopausal symptoms were reduced in the same manner in both groups . There were no statistically significant differences in the mean plasma estradiol and estrone concentrations between the two treatment groups after 10 weeks of therapy . The mean estradiol to estrone ratio was similar in both groups , as was the number of adverse events observed . In summary , Menorest was as effective as an oral estrogen in alleviating menopausal symptoms Objective To compare the efficacy and patient acceptability of intranasal versus transdermal 17β-estradiol ( E2 ) delivery systems for postmenopausal symptoms . Methods Postmenopausal women were r and omly assigned to intranasal 17β-E2 , 300 μg daily ( n = 176 ) or transdermal 17β-E2 ( delivering 50 μg/day ) , two patches per week ( n = 185 ) for 12 weeks , followed by a 4-week period with the alternate treatment . Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12 . Patient acceptability was compared by patient choice of administration route and by question naire at week 16 . Results Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12 . Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups ( P < .001 ) . The difference between groups in the Kupperman Index score of −0.5 ± 0.9 ( 95 % confidence interval −2.3 , 1.3 ) was within the predetermined interval of equivalence . Both therapies were well tolerated with similar adverse event rates , except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 ( 7.2 % ) than with the patch ( 15.5 % , P = .02 ) . Sixty-six percent of patients chose to continue the intranasal therapy and 34 % the transdermal therapy ( P < .001 ) . Satisfaction was greater with intranasal therapy at week 16 ( P < .001 ) . Conclusion Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles . Intranasal therapy was the patients ' choice for long-term treatment OBJECTIVE Our purpose was to evaluate the efficacy and safety of 3 dosages of Esclim , delivering 0.025 mg , 0.050 mg , or 0.100 mg 17beta-estradiol per 24 hours , in the treatment of moderate to severe vasomotor symptoms . STUDY DESIGN In this double-blind , placebo-controlled , parallel-group , multicenter trial , 196 highly symptomatic menopausal women received 12 weeks of continuous unopposed treatment with 1 of the 3 dosages of Esclim or a matching placebo patch . RESULTS The reduction in frequency of moderate to severe vasomotor symptoms was statistically significant compared with placebo ( P < .05 ) from week 2 onward in the Esclim 50 and 100 groups and from week 3 onward in the Esclim 25 group . Symptom severity was also reduced . Estrogen-related adverse events , particularly metrorrhagia and endometrial hyperplasia , were less frequent in the Esclim 25 group than in the higher-dosage groups . CONCLUSION All 3 dosages of Esclim were effective in the treatment of vasomotor symptoms . The efficacy and safety of Esclim 25 indicate a good risk-benefit ratio Objective : To determine the optimal dose , safety , and efficacy of an estrogen receptor & bgr ; selective Chinese herbal extract , menopausal formula 101 ( MF101 ) , for treating hot flushes . Methods : A r and omized , blinded trial in 217 postmenopausal women with hot flushes r and omized to 5 or 10 g/day of MF101 or placebo for 12 weeks . Results : The effects of 5 g/day of MF101 did not differ from those of placebo . After 12 weeks , the mean percent decrease in frequency of hot flushes in the 10 g/day group was 12.9 % greater than that in the placebo group ( P = 0.15 ) , the median percent decrease was 11.7 % greater than that in the placebo group ( P = 0.05 ) , and the proportion of women with at least a 50 % reduction in hot flushes was 16.2 % greater than that in the placebo group ( P = 0.03 ) . Conclusions : Treatment with 10 g/day of MF101 reduces the frequency of hot flushes . Trials with higher doses are planned Despite the widespread use of hormone replacement therapy , various reports on its side effects have generated an increasing interest in the development of safe natural agents for the management of postmenopausal discomforts . The present r and omized , double-blinded , placebo-controlled study investigated the effect of 90-day supplementation of a st and ardized extract of fenugreek ( Trigonella foenum-graecum ) ( FenuSMART ™ ) , at a dose of 1000 mg/day , on plasma estrogens and postmenopausal discomforts . Eighty-eight women having moderate to severe postmenopausal discomforts and poor quality of life ( as evidence d from the scores of Greene Climacteric Scale , short form SF-36 ® and structured medical interview ) were r and omized either to extract-treated ( n = 44 ) or placebo ( n = 44 ) groups . There was a significant ( p < 0.01 ) increase in plasma estradiol ( 120 % ) and improvements on various postmenopausal discomforts and quality of life of the participants in the extract-treated group , as compared with the baseline and placebo . While 32 % of the subjects in the extract group reported no hot flashes after supplementation , the others had a reduction to one to two times per day from the baseline stages of three to five times a day . Further analysis of haematological and biochemical parameters revealed the safety of the extract and its plausible role in the management of lipid profile among menopausal women . Copyright © 2016 John Wiley & Sons , Objective To determine the efficacy and local tolerance of a new matrix transdermal drug-delivery system that delivers 0.02 mg of 17β-estradiol ( E2 ) daily for 7 days for the relief of vasomotor symptoms . Methods A total of 324 surgically or naturally menopausal women , all with prior hysterectomy and moderate to severe vasomotor symptoms ( 56 - 140 hot flushes per week , with episodes of sweating , during a baseline observation period ) , participated in two independent , 12-week , r and omized , double-blind , placebo-controlled studies . After a 4-week , treatment-free period , each woman received a continuous regimen of either one E2 transdermal system , two E2 transdermal systems , or placebo transdermal system(s ) applied every week for 12 weeks . Efficacy was measured as reduction in hot flush frequency , determined from subject diaries . To measure local tolerance , skin irritation ( erythema and edema ) was objective ly and systematic ally evaluated under blue light after removal of the transdermal system(s ) . Serum E2 and estrone concentrations were determined in one of the studies during baseline and on days 1 , 9 , 30 , 58 , 79 , and 84 . Results Mean hot flush frequency decreased from 80 hot flushes per week at baseline to approximately 13 hot flushes per week ( 84 % decrease ) after 12 weeks of transdermal E2 treatment . Compared with placebo , the decrease in hot flush frequency was significant as early as weeks 2 and 3 , and was maintained through the end of the study . Few clinical ly significant skin reactions occurred , and only nine ( 3 % ) of the subjects withdrew because of a skin effect . After initial increase , serum E2 concentrations remained stable throughout the study , achieving values of approximately 20 and 40 pg/mL above baseline for one and two E2 transdermal systems , respectively . Conclusion The E2 transdermal system effectively reduced the frequency of moderate to severe vasomotor symptoms as early as the second week of therpy and was very well tolerated . The decrease in hot flush frequency was similar to that reported for oral and other transdermal estrogens , but at lower serum E2 concentrations . This result may be due to the stable E2 blood level achieved with this transdermal system OBJECTIVES Raloxifene is approved for the treatment and prevention of postmenopausal osteoporosis . Previous studies have described a raloxifene-associated increase in hot flushes , reported as adverse events . This study was undertaken to provide a detailed evaluation of the potential of raloxifene to induce or exacerbate hot flushes in postmenopausal women . STUDY DESIGN In this double-blind , placebo-controlled , parallel group multicenter study , 487 postmenopausal women were r and omized to receive 8 months of treatment with either raloxifene ( RLX ) at the recommended dose of 60 mg/day , or by slow-dose escalation for the first 2 months , followed by the st and ard dose for the rest of the study ( SDE ) , or placebo ( PL ) . The frequency , duration , intensity , severity , and impact of hot flushes were measured . RESULTS With 3 - 5 hot flushes per week , the mean number at baseline was low . During treatment , it increased by < 1 hot flush/week in both active treatment groups and decreased by < 1 hot flush/week with PL . The high proportion ( approximately 60 % ) of asymptomatic patients at baseline had increased further by the end of treatment in all groups . The proportion of women whose pre-existing hot flushes abated during treatment was significantly greater with SDE ( P=.005 ) and PL ( P=.050 ) , but not with RLX , when compared with the proportion with treatment-emergent flushes . There were no statistically significant between-group differences in the distribution of the number of hot flushes after 2 months of treatment . At end point , there were no significant differences between SDE and either RLX or PL , but the difference between RLX and PL was statistically significant ( P=.035 ) . There were no significant between-group differences in the hot flush impact scores , in treatment satisfaction , and in the proportion of patients requesting symptomatic treatment to alleviate hot flushes . CONCLUSION In a postmenopausal population meeting the criteria for the prescription of RLX , the overall effect of the drug on hot flushes is low . Previous studies using adverse event reports have overestimated the importance of hot flushes in postmenopausal women during treatment with RLX . Slow-dose escalation seems to decrease the number of symptomatic patients further and may be a useful strategy in women reporting flushes when starting RLX BACKGROUND Most women receiving systemic therapy for breast cancer experience hot flashes . We undertook a r and omised , double-blind , placebo-controlled , multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer . METHODS 420 women with breast cancer who were having two or more hot flashes per day were r and omly assigned placebo , gabapentin 300 mg/day , or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks . Each patient kept a 1-week , self-report diary on the frequency , severity , and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment . Analyses were by intention to treat . FINDINGS Evaluable data were available on 371 participants at 4 weeks ( 119 placebo , 123 gabapentin 300 mg , and 129 gabapentin 900 mg ) and 347 at 8 weeks ( 113 placebo , 114 gabapentin 300 mg , and 120 gabapentin 900 mg ) . The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8 , respectively were : 21 % ( 95 % CI 12 to 30 ) and 15 % ( 1 to 29 ) in the placebo group ; 33 % ( 23 to 43 ) and 31 % ( 16 to 46 ) in the group assigned gabapentin 300 mg ; and 49 % ( 42 to 56 ) and 46 % ( 34 to 58 ) in the group assigned gabapentin 900 mg . The differences between the groups were significant ( p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect , adjusted for baseline values ) ; only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity . INTERPRETATION Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day , but not at a dose of 300 mg/day . This drug should be considered for treatment of hot flashes in women with breast cancer PURPOSE Most breast cancer survivors experience hot flashes ; many use complementary or alternative remedies for these symptoms . We undertook a r and omized clinical trial of black cohosh , a widely used herbal remedy for menopausal symptoms , among breast cancer patients . PATIENTS AND METHODS Patients diagnosed with breast cancer who had completed their primary treatment were r and omly assigned to black cohosh or placebo , stratified on tamoxifen use . At enrollment , patients completed a question naire about demographic factors and menopausal symptoms . Before starting to take the pills and at 30 and 60 days , they completed a 4-day hot flash diary . At the final visit , they completed another menopausal symptom question naire . Follicle-stimulating hormone ( FSH ) and luteinizing hormone ( LH ) levels were measured in a subset of patients at the first and final visits . RESULTS Of 85 patients ( 59 on tamoxifen , 26 not on tamoxifen ) enrolled in the study , 42 were assigned to treatment and 43 were assigned to placebo ; 69 completed all three hot flash diaries . Both treatment and placebo groups reported declines in number and intensity of hot flashes ; the differences between the groups were not statistically significant . Both groups also reported improvements in menopausal symptoms that were , for the most part , not significantly different . Changes in blood levels of FSH and LH also did not differ in the two groups . CONCLUSION Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms , including number and intensity of hot flashes . Our study illustrates the feasibility and value of st and ard clinical trial methodology in assessing the efficacy and safety of herbal agents PURPOSE Up to 75 % of women experience hot flashes , which can negatively impact quality of life . As hot flash physiology is not definitively understood , it can not be assumed that effective agents represent class effects . Therefore , there is a continued need for rigorous evaluation to identify effective nonhormonal options for hot flash relief . METHODS A r and omized , double-blind trial evaluated citalopram at target doses of 10 , 20 , or 30 mg/d versus placebo for 6 weeks . Postmenopausal women with at least 14 bothersome hot flashes per week recorded hot flashes for 7 days before starting treatment and were then titrated to their target doses . The primary end point was the change from baseline to 6 weeks in hot flash score . RESULTS Two hundred fifty-four women were r and omly assigned onto this study . Data for hot flash scores and frequencies showed significant improvement in hot flashes with citalopram over placebo , with no significant differences among doses . Reductions in mean hot flash scores were 2.0 ( 23 % ) , 7.0 ( 49 % ) , 7.7 ( 50 % ) , and 10.7 ( 55 % ) for placebo and 10 , 20 , and 30 mg of citalopram , respectively ( P < or= .002 ) . Improvement in secondary outcomes , such as the Hot Flash Related Daily Interference Scale , was statistically superior in the 20-mg arm . Citalopram was well-tolerated , with no significant negative adverse effects . CONCLUSION Citalopram is an effective , well-tolerated agent in managing hot flashes . There does not appear to be a significant dose response above 10 mg/d , but broader helpful effects of the agent appear to be more evident at 20 mg/d OBJECTIVES To compare the efficacy and safety of the black cohosh root extract Cr 99 with placebo in women with climacteric complaints . METHODS A multicenter , r and omized , placebo-controlled , double-blind , parallel group study was conducted in 122 menopausal women ( intention-to-treat population ) with > or =3 hot flashes a day , treated over 12 weeks . Two main efficacy measures - weekly weighted score of hot flashes and Kupperman Index - and secondary efficacy variables , e.g. Menopause Rating Scale , were defined . Routine safety laboratory parameters and adverse events were documented . RESULTS The primary efficacy analysis showed no superiority of the tested black cohosh extract compared to placebo . However , in the subgroup of patients with a Kupperman Index > or = 20 a significant superiority regarding this index could be demonstrated ( P<0.018 ) . A decrease of 47 % and 21 % was observed in the black cohosh and placebo group , respectively . The weekly weighted scores of hot flashes ( P<0.052 ) and the Menopause Rating Scale ( P<0.009 ) showed similar results . Prevalence and intensity of the adverse events did not differ in the two treatment groups . CONCLUSIONS The results indicate a superiority of the tested Cimicifuga racemosa extract compared to placebo in patients with menopausal disorders of at least moderate intensity according to a Kupperman Index > or = 20 , but not in the intention-to-treat population as a whole PURPOSE Prior progestin studies treating hot flashes in women have been short duration and single dose . This study tests the progestin megestrol acetate ( MA ) at two doses versus placebo over 6 months . PATIENTS AND METHODS Patients with T1 - 3 , N0 - 1 , M0 breast cancer were eligible after completion of surgery and chemotherapy and at least 4 months of tamoxifen ( if prescribed ) . Women were required to have at least 10 hot flashes of any severity or at least five severe episodes per week . Patients were r and omly assigned to placebo , MA 20 mg , or MA 40 mg for 3 months . Success at 3 months was defined as completion of treatment with a > or= 75 % reduction in hot flashes from baseline . If success was achieved , drug treatment for another 3 months was given on the same blinded arm ; if not , open-label MA 20 mg was added to blinded study drug and continued for 3 months . Other menopausal symptoms were also assessed . RESULTS Two hundred eighty eight eligible women were r and omly assigned ( 286 eligible ) , of whom 85 % were on tamoxifen , 40 % had over 63 hot flashes/week , and 75 % had vasomotor symptoms for > or= 6 months . Success at 3 months was 14 % on placebo , 65 % on 20 mg , and 48 % on 40 mg ( both MA doses superior to placebo ; P < .0001 ) . Most successes at 3 months were maintained at 6 months ( 77 % on 20 mg and 81 % on 40 mg ) . CONCLUSION MA significantly reduced vasomotor symptoms with durable benefit over 6 months . MA 20 mg/d is the preferred dose . There was no significant impact on other menopausal symptoms Objective : To investigate the efficacy and safety of the special extract ERr 731 from the roots of Rheum rhaponticum compared to placebo in perimenopausal women with climacteric complaints . Design : A multicenter , prospect i ve , r and omized , double-blind , placebo-controlled , clinical trial in which 109 women with climacteric complaints received either one enteric-coated tablet of ERr 731 ( n = 54 ) or placebo ( n = 55 ) daily for 12 weeks . Primary outcome criterion for efficacy was the change in Menopause Rating Scale II ( MRS II ) total score after 12 weeks . Other efficacy assessment s analyzed number and severity of hot flushes , menopause-specific quality of life , number of bleeding/spotting days , and treatment outcome . Results : By 12 weeks , the MRS II total score and each MRS II symptom significantly decreased in the ERr 731 group compared to the placebo group ( P < 0.0001 ) . After 4 weeks , ERr 731 also significantly decreased the number and severity of hot flushes ( P < 0.0001 ) . After 12 weeks , the overall menopause-specific quality of life was significantly better in women treated with ERr 731 compared with placebo ( P < 0.05 ) . Treatment outcome assessed by investigators and participants was better in the ERr 731 group , and ERr 731 was better tolerated than placebo . There were no differences in gynecological findings including endometrial biopsies , bleeding , weight , blood pressure , pulse , and laboratory safety parameters between the treatment groups . No adverse events were classified as being related to the investigational medication . Conclusions : Compared to placebo , ERr 731 significantly reduces the occurrence and severity of climacteric complaints in perimenopause . It is also safe and well tolerated Hot flushes and night sweats are one of the main symptoms accompanying the menopause , and are a main reason for seeking medical help at this time . This study of 61 women ( reporting hot flushes once a week or more ) investigates dimensions of subjective reporting using open questions and rating scales . Two separate factors were delineated using a principal component factor analysis - frequency ( of hot flushes and night sweats ) and problem ratings ( of distress , interference and perception of flushes as problematic ) - which had high test-retest reliability . The frequency ratings correlated highly with prospect i ve daily monitoring . Depressed mood , anxiety and low self-esteem , but not frequency , discriminated between those who regarded flushes as problematic and those who did not . It is suggested that these two subjective measures should be used in assessment and in evaluation of hormonal and psychological interventions Objective : This study aim ed to compare the efficacy and safety of a multibotanical ( Nutrafem ) with those of placebo for the treatment of menopausal vasomotor symptoms . Methods : In this phase III , double-blind , r and omized , placebo-controlled study , 159 postmenopausal women experiencing at least 21 vasomotor symptoms per week were treated with Nutrafem ( Bionutra Pte Ltd , Singapore ) or a matched placebo for 12 weeks . Treatment outcome was evaluated by the change from baseline in the average weekly number of vasomotor symptoms . Results : At the end of the study , Nutrafem reduced the number of vasomotor symptoms by 46 % from baseline , and this is significantly superior to placebo ( 26 % from baseline ; P = 0.020 ) . Forty-three percent of women taking Nutrafem experienced an at least 50 % reduction in the number of symptoms compared with 6 % of women taking placebo ( P = 0.021 ; number needed to treat = 2.7 ) . There were no group differences in adverse events , laboratory values , and gynecological data . Conclusions : Nutrafem is an effective botanical treatment for vasomotor symptoms in postmenopausal women Objective : Phase 3 studies of postmenopausal women with or at risk for osteoporosis reported that , compared with placebo , bazedoxifene increased the incidence of hot flushes . The current study evaluated the vasomotor effects of bazedoxifene in healthy nonflushing postmenopausal women . Methods : In this phase 2 study , nonflushing postmenopausal women ( n = 494 ) were r and omized to daily treatment with bazedoxifene 5 , 10 , or 20 mg ; raloxifene 60 mg ; or placebo for 12 weeks . The primary endpoint was the percentage of women reporting hot flushes at any time during the study ; secondary endpoints included the mean number and severity of hot flushes and the mean number of days with hot flushes . Effects on bone turnover markers and lipid parameters were also evaluated . Results : Over the 12-week study , 25.5 % of placebo-treated women reported hot flushes . The incidence of hot flushes with bazedoxifene 5 , 10 , and 20 mg and raloxifene 60 mg was 26.0 % , 33.7 % , 27.6 % , and 21.4 % , respectively , with no significant differences from that with placebo . The active treatment groups showed no significant differences from placebo in the mean number or severity of hot flushes during week 12 or any 4-week period . Bazedoxifene and raloxifene showed beneficial effects on lipid parameters and markers of bone turnover . All doses of bazedoxifene were generally well tolerated and did not increase endometrial thickness , vaginal bleeding , or breast pain compared with placebo over 12 weeks of therapy . Conclusions : Data from this phase 2 clinical trial suggest that bazedoxifene does not increase the incidence of hot flushes relative to placebo in nonflushing postmenopausal women Objective : To assess the efficacy and safety of topical micellar nanoparticle estradiol emulsion ( MNPEE ; Estrasorb ; Novavax , Inc. , Malvern , PA ) in postmenopausal women with moderate to severe vasomotor symptoms . Design : A multicenter , r and omized , double-blind , placebo-controlled study was conducted in 200 postmenopausal women with seven or more moderate to severe hot flushes per day . The study consisted of a 3-week screening period followed by a 1-week placebo emulsion run-in period and a 12-week active or placebo treatment period . Women were r and omized ( 1:1 ) to receive MNPEE ( 3.45 g daily dose of emulsion containing 8.6 mg estradiol ) or matching placebo emulsion . The primary efficacy variable was the change from baseline in the frequency of moderate and severe hot flushes at weeks 4 and 12 . Adverse events were monitored throughout the trial . Results : Topical micellar nanoparticle estradiol emulsion was statistically significantly superior to placebo emulsion in reducing the mean frequency of moderate to severe vasomotor symptoms by week 3 ( P = 0.003 ) , with superiority to placebo maintained from weeks 4 to 12 ( P < 0.001 ) . At week 12 ( peak benefit ) , MNPEE reduced mean daily frequency of hot flush count by 11.1 ( P < 0.001 vs placebo ) . MNPEE significantly reduced mean symptom severity from weeks 4 to 12 ( P < 0.001 ) compared with placebo . At endpoint , mean serum concentrations of estradiol and estrone were 63 and 89 pg/mL , respectively , in the MNPEE group . The mean endpoint ratio of estradiol to estrone in these patients was 0.774 . MNPEE was safe and well tolerated . Conclusion : Once-daily application of 3.45 g of micellar nanoparticle estradiol emulsion containing 8.6 mg of estradiol was safe and effective in providing significant relief of vasomotor symptom frequency and severity in postmenopausal women CONTEXT Clinical trials demonstrating increased risk of cardiovascular disease and breast cancer among women r and omized to hormone replacement therapy have increased interest in other therapies for menopausal symptoms . Dietary supplements containing isoflavones are widely used as alternatives to hormonal therapies for hot flashes , but there is a paucity of data supporting their efficacy . OBJECTIVE To compare the efficacy and safety of 2 dietary supplements derived from red clover with placebo in symptomatic menopausal women . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of menopausal women , aged 45 to 60 years , who were experiencing at least 35 hot flashes per week . The study was conducted between November 1999 and March 2001 at 3 US medical centers and included women who were recently postmenopausal ( mean [ SD ] , 3.3 [ 4.5 ] years since menopause ) experiencing 8.1 hot flashes per day . Women were excluded if they were vegetarians , consumed soy products more than once per week , or took medications affecting isoflavone absorption . INTERVENTION After a 2-week placebo run-in , 252 participants were r and omly assigned to Promensil ( 82 mg of total isoflavones per day ) , Rimostil ( 57 mg of total isoflavones per day ) , or an identical placebo , and followed-up for 12 weeks . MAIN OUTCOME MEASURE The primary outcome measure was the change in frequency of hot flashes measured by participant daily diaries . Secondary outcome measures included changes in quality of life and adverse events . RESULTS Of 252 participants , 246 ( 98 % ) completed the 12-week protocol . The reductions in mean daily hot flash count at 12 weeks were similar for the Promensil ( 5.1 ) , Rimostil ( 5.4 ) , and placebo ( 5.0 ) groups . In comparison with the placebo group , participants in the Promensil group ( 41 % ; 95 % confidence interval [ CI ] , 29%-51 % ; P = .03 ) , but not in the Rimostil group ( 34 % ; 95 % CI , 22%-46 % ; P = .74 ) reduced hot flashes more rapidly . Quality -of-life improvements and adverse events were comparable in the 3 groups . CONCLUSION Although the study provides some evidence for a biological effect of Promensil , neither supplement had a clinical ly important effect on hot flashes or other symptoms of menopause OBJECTIVES To compare the effects of daily ingestion of dietary soy supplementation , low-dose hormone therapy ( HT ) and placebo on psychological , somatic and urogenital symptoms in postmenopausal women . STUDY DESIGN A double-blind , r and omized , controlled trial . Sixty healthy , symptomatic , postmenopausal women of 40 - 60 years of age were allocated to use dietary soy supplementation ( containing 90 mg of isoflavone ) or HT ( 1 mg estradiol and 0.5 mg norethisterone acetate ) or placebo . MAIN OUTCOME MEASURES the Menopause Rating Scale ( MRS ) was used to assess menopausal symptoms at baseline and after 16 weeks of treatment . Intention-to-treat analyses were performed using the chi-square test , Fisher 's exact test , the Kruskal-Wallis non-parametric test and analysis of variance ( ANOVA ) . RESULTS No statistically significant differences were found between the groups with respect to baseline clinical and sociodemographic characteristics . The psychological , somatic and urogenital symptoms analyzed in the MRS improved during treatment in all the groups , except for urogenital symptoms in the placebo group in which no significant changes were detected . Comparison between groups revealed a statistically significant improvement in somatic symptoms ( hot flashes and muscle pain ) in the users of HT ( -45.6 % ) and dietary soy supplementation ( -49.8 % ) . Urogenital symptoms ( vaginal dryness ) improved significantly in HT users ( -38.6 % ) and in users of the dietary soy supplementation ( -31.2 % ) . There was no statistically significant difference between the groups with respect to overall MRS score or to scores obtained in the psychological symptoms subscale . CONCLUSION Dietary soy supplementation may constitute an effective alternative therapy for somatic and urogenital symptoms of the menopause OBJECTIVE : To compare efficacy and safety of desvenlafaxine succinate ( desvenlafaxine ) with placebo for the treatment of vasomotor symptoms . METHODS : This r and omized , double-blind , placebo-controlled trial enrolled 707 healthy , postmenopausal women experiencing 50 or more moderate-to-severe hot flushes per week . Participants r and omly received desvenlafaxine 50 , 100 , 150 , or 200 mg or placebo daily . Trial duration was 52 weeks . Primary outcomes were change from baseline in average daily number of moderate-to-severe hot flushes and in daily hot flush severity score at weeks 4 and 12 . RESULTS : Six hundred twenty women with an average of 11 moderate-to-severe hot flushes per day at baseline completed at least one on-therapy evaluation for primary efficacy end points ; 519 participants completed 12 weeks of treatment , and 368 completed the study . Desvenlafaxine 100 mg/d achieved a significantly greater reduction compared with placebo in average daily number of hot flushes at weeks 4 ( P=.013 ) and 12 ( P=.005 ) , reaching a 64 % decrease from baseline at week 12 , and the 75 % responder rate was significantly higher for desvenlafaxine 100 mg ( 50 % ) compared with placebo ( 29 % ; P=.003 ; number needed to treat=4.7 ) at week 12 . Average daily severity of hot flushes was significantly lower in the desvenlafaxine 100-mg group compared with placebo at week 12 ( P=.020 ) . Desvenlafaxine-treated women reported significantly more treatment-emergent adverse events than placebo-treated women during the first week of therapy only . CONCLUSION : Desvenlafaxine is an effective nonhormonal treatment for vasomotor symptoms in postmenopausal women . Its tolerability profile is consistent with that of other serotonin-norepinephrine reuptake inhibitors . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00421031 LEVEL OF EVIDENCE : Abstract Determine the efficacy and tolerability of omega-3 fatty acids versus soybean isoflavones in reducing the vasomotor symptoms ( VMSs ) frequency in postmenopausal women . A r and omized , prospect i ve , two-arm study was performed in healthy postmenopausal women aged 45–65 . The two arms were : two capsules/day of omega-3 ( 425 mg of omega-3/capsule ) administered orally ( n = 38 ) and two tablets/day of soybean isoflavones ( 54.4 mg of isoflavones/tablet ) ( n = 30 ) , over 16 weeks . The mean baseline frequency of moderate and severe VMSs per week in the omega-3 group was 24.56 and 23.90 , respectively , and 19.65 and 19.51 in the isoflavone group . After 4 months , the reduction in moderate and severe hot flashes with omega-3 was significant ( p < .001 ) , whereas in the case of isoflavones , there was a significant difference in severe ( p = .02 ) hot flashes after 4 months , but not in moderate hot flashes ( p = .077 ) . Omega-3 did not demonstrate significant efficacy differences versus isoflavones over time . The use of omega-3 has a beneficial effect on hot flash reduction after 4 months of treatment . This is comparable to the benefits found with soybean isoflavones after 3–4 weeks and after 4 months in severe hot flash women , but higher than those found with soybean isoflavones in moderate symptom women Objectives To determine the effect of acupuncture in treating hot flushes in perimenopausal or postmenopausal women . Methods The study was a r and omised single-blind sham-controlled clinical trial . Perimenopausal or postmenopausal women with moderate or severe hot flushes were r and omised to receive real or sham acupuncture . Both groups underwent a 4-week run-in period before the treatment . The real acupuncture group received 11 acupuncture treatments for 7 weeks , and the control group underwent sham acupuncture on non-acupuncture points during the same period . Both groups were followed for 8 weeks after the end of treatment period . Changes from baseline in the hot flush scores at week 7 , measured by multiplying the hot flush frequency and severity , were the primary outcome . Hot flush frequency , severity and menopause-related symptoms measured with the Menopause Rating Scale Question naire were regarded as secondary outcomes . Results 54 participants were r and omised into the real acupuncture group ( n=27 ) and the sham acupuncture group ( n=27 ) . The mean change in hot flush scores was −6.4±5.2 in the real acupuncture group and −5.6±9.2 in the sham group at week 7 from values at the start of the acupuncture treatment ( 10.0±8.1 vs 11.7±12.6 ) , respectively ( p=0.0810 ) . No serious adverse events were observed during the whole study period . Conclusions Compared to sham acupuncture , acupuncture failed to show significantly different effects on the hot flush scores but showed partial benefits on the hot flush severity . Further consideration is needed to develop appropriate strategies for distinguishing non-specific effects from observed overall effectiveness of acupuncture for hot flushes . Whether acupuncture has point-specific effects for hot flushes should be also considered in design ing future research es OBJECTIVE : To examine the efficacy of extended-release venlafaxine for the treatment of postmenopausal hot flushes . METHODS : Eighty postmenopausal women with more than 14 hot flushes per week were r and omized to receive treatment with extended-release venlafaxine or placebo . Participants received 37.5 mg daily for 1 week , followed by 75 mg daily for 11 weeks . Daily hot flush severity scores and adverse effects were recorded by subjects . Baseline and monthly follow-up question naires assessed patient-perceived hot flush score , quality of life , and sexual function . Participants were treated for 12 weeks . RESULTS : Of the 80 subjects who enrolled in the study , 40 were in the treatment group and 40 in the control group . Of these , 61 completed the study ( treatment , n = 29 ; control , n = 32 ) . Subjective assessment at monthly visits of the effects of hot flush symptoms on daily living were significantly improved in the treatment group ( P < .001 ) . Hot flush severity scores based on daily diaries were somewhat lower in the treatment group , but the between-group difference did not reach statistical significance ( P = .25 ) . Three side effects , dry mouth , sleeplessness , and decreased appetite , were significantly more frequent in the venlafaxine group , but others , including dizziness , tremors , anxiety , diarrhea , and rash , were significantly less frequent . Ninety-three percent of participants in the venlafaxine group chose to continue treatment at the conclusion of the study . CONCLUSION : Extended-release venlafaxine , 75 mg per day , is an effective treatment for postmenopausal hot flushes in otherwise healthy women , based on a significant decrease in patient-perceived hot flush score . LEVEL OF EVIDENCE : OBJECTIVE To investigate the recurrence and severity of climacteric symptoms after two methods of discontinuation of prolonged hormone therapy . DESIGN Postmenopausal women treated with hormone therapy for more than 3 years and opting to discontinue therapy were r and omly assigned to two treatment groups . Hormone therapy was discontinued either abruptly ( group 1 ) or gradually ( group 2 ) . Symptoms in both groups were monitored with the Greene climacteric scale at 1 , 3 , 6 , 9 , and 12 months . RESULTS Ninety-one women aged 48 to 73 years ( mean age 56.8 + /- 4.2 years ) participated in the study . The mean therapy duration was 8.8 + /- 3.8 years . No differences were noted between the two groups regarding age at menopause , body mass index , reasons to start therapy , hormone therapy duration , type of regimen , and reasons cited for hormone treatment discontinuation . After cessation of therapy , a similar percentage of patients in each group resumed hormone therapy . Climacteric syndromes , specifically vasomotor dysfunction , were more severe in group 1 than in group 2 during the first 3 months after hormone therapy withdrawal . However , by 6 months vasomotor symptoms were worse in group 2 . By 9 to 12 months , no difference was noted between groups . No differences were observed in the percentage of weight gain , vaginal bleeding , and atrophy after discontinuation of therapy by either method . CONCLUSIONS Our specific regimen of gradual discontinuation of hormone therapy merely postponed , and neither prevented nor minimized , the reappearance of vasomotor symptoms , mood deterioration , and sexual dysfunction , and the result ing discomfort BACKGROUND The benefit of oestrogen therapy for menopause symptoms is well recognised . However , the means of delivery currently available have disadvantages , including variable bioavailability , intestinal and hepatic first-pass effects , and dermatological reactions . An intranasal 17beta-oestradiol spray , S21400 , which bypasses such drawbacks , has been developed . We studied the efficacy and tolerability of S21400 in the treatment of postmenopausal symptoms . METHODS In this double-blind study , 420 postmenopausal women were r and omly allocated to receive intranasal placebo or S21400 in doses of 100 microg , 200 microg , 300 microg , or 400 microg , or oral oestradiol valerate in doses of 1 mg or 2 mg , daily for 12 weeks . The primary outcomes were the Kupperman Index ( KI ) and the incidence of hot flushes . Tolerability assessment s included rhinoscopy and ciliary function tests . FINDINGS S21400 dose-dependently decreased KI ( p<0.001 ) , with a lowest effective dose of 300 microg/day at 4 weeks ( p<0.05 ) and 200 microg/day at 12 weeks ( p<0.01 ) . The incidence of hot flushes decreased by a maximum of 75 % ( S21400 lowest effective dose 200 microg/day at 4 weeks and 100 microg/day at 12 weeks ) . S21400 increased serum oestradiol exposure dose-dependently , to concentrations similar to those achieved with oral oestradiol 1 - 2 mg , with lower intra-patient and inter-patient variability . There was no significant difference in ear , nose , and throat function or adverse events between the S21400 and the placebo or oral oestradiol groups , except for a greater incidence of sneezing and application site reaction ( 99 % mild or moderate ) in the S21400 groups . S21400 was thought to be effective and convenient by the patients , and compliance was high . INTERPRETATION Intranasally administered 17beta-oestradiol is significantly better than placebo ; its effectiveness at reducing menopausal symptoms is similar to that of oral oestradiol and is also well-tolerated . Intranasal administration avoids first-pass metabolism and provides a reproducible , easily adjustable dosing mechanism that represents a new option for hormone replacement therapy Objectives To evaluate the effects of acupuncture and sham-acupuncture on women with menopausal symptoms as reflected in the intensity of their hot flushes and the Kupperman Menopausal Index ( KMI ) . Method This was a r and omized , single-blind , placebo-controlled , cross-over trial with 81 patients assigned to two groups : Group 1 received 12 months of acupuncture , then 6 months of sham-acupuncture treatment ( n = = 56 ) and Group 2 received 6 months of sham-acupuncture , then 12 months of acupuncture treatment ( n = = 25 ) . The needles were inserted in a harmonic craniocaudal manner at a depth of about 2 cm , and each session lasted approximately 40 min . The efficacy of acupuncture in ameliorating the climacteric symptoms of patients in postmenopause was determined through the KMI and the intensity of hot flushes . The analysis of variance method for two factors and repeated measures was applied . Results The baseline values of the women in both groups were similar for the KMI score and number of hot flushes . At the end of 6 months , the values for the KMI and hot flushes for the women in Group 1 were lower than those of the women in Group 2 ( p < 0.05 ) . After 12 months , the KMI and hot flush data were similar in both groups . After 18 months , the values of the KMI and hot flushes for the women in Group 2 for were lower than those of the women in Group 1 ( p < 0.05 ) . Conclusion Acupuncture treatment for relieving menopausal symptoms may be effective for decreasing hot flushes and the KMI score in postmenopausal women Objective To determine whether there is a significant reduction in frequency and severity of hot flashes in symptomatic postmenopausal women who are administered continuously different dose combinations of norethindrone acetate and ethinyl estradiol . Design Two r and omized clinical trials ( Study 1 and Study 2 ) were conducted in which study participants recorded in daily diaries the frequency of their hot flashes . Study 2 participants also recorded the number of mild , moderate , or severe hot flashes they experienced . In Study 1 , a total of 219 postmenopausal women reporting vasomotor symptoms were placed r and omly into groups to receive either a placebo or 1 of 4 treatments ( 0.2 mg /1 & mgr;g ; 0.5 mg/2.5 & mgr;g ; 1 mg/5 & mgr;g ; or 1 mg/10 & mgr;g norethindrone acetate/ethinyl estradiol ) . In Study 2 , a total of 266 highly symptomatic postmenopausal women were placed r and omly to receive either a placebo or 1 of 3 treatment groups [ 0.5 mg/2.5 & mgr;g ; 1 mg/5 & mgr;g ; or 1 mg/10 & mgr;g norethindrone acetate (NA)/ethinyl estradiol ( EE ) ] . Total duration of treatment was 16 weeks in Study 1 and 12 weeks in Study 2 . Study 1 subjects had to have at least 10 hot flashes during the week before r and omization . Study 2 subjects had to have at least 56 moderate to severe hot flashes during the week before r and omization . Results In both studies , there was a dose-related decrease in hot flash frequency with the highest dose ( 1 mg NA/10 & mgr;g EE ) group that had the greatest response . Significant differences from placebo ( p < 0.05 , Dunnett 's test ) occurred within 4 weeks in Study 1 for hot flash frequency with a percent reduction in frequency ranging from 33 % for placebo to 84 % for both the 1 mg NA/10 & mgr;g EE and 1 mg NA/5 & mgr;g EE dose groups . Likewise , Study 2 significant reductions in hot flash frequency occurred by Week 2 for 1 mg NA/10 & mgr;g EE , Week 3 for 1 mg NA/5 & mgr;g EE , and Week 5 for 0.5 mg NA/2.5 & mgr;g EE ( p < 0.05 , Dunnett 's test ) . This dose effect was also apparent with regard to severity . In addition , more subjects had clinical ly meaningful reductions in hot flash frequency or elimination as the dose combinations increased . Conclusion There were significant reductions in hot flash frequency and severity with continuous treatment with norethindrone acetate and ethinyl estradiol combinations . The time at which significant reductions were observed , as well as the magnitude of the response , were dose dependent . The opportunity for lower-dose options of a new continuous-combined hormone replacement therapy provides therapeutic flexibility for women who are recently menopausal Abstract Objectives : This study assessed the effects of oral porcine placental extract ( PPE ) on the mild menopausal symptoms of climacteric women . Methods : In this 12-week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study , 50 climacteric Japanese women were r and omized 1 : 1 to oral PPE ( 300 mg/day ) or placebo . Menopausal symptoms were evaluated by using the Simplified Menopausal Index ( SMI ) , as were serum estradiol ( E2 ) and follicle stimulating hormone ( FSH ) levels . Blood biochemical and cellular and urinary tests were done to evaluate safety aspects of repeated oral administration of PPE . Results : The total SMI score of the PPE group was significantly more improved after 12 weeks than that of the placebo group ( p = 0.031 ) . This score and three subscores ( vasomotor , psychological , and somatic symptoms ) were significantly improved at 8 and /or 12 weeks compared with the initial values in the PPE group ( p < 0.05 ) . E2 and FSH levels were not improved in either group . No adverse events were observed . Conclusions : Oral PPE at 300 mg/day improved the mild menopausal symptoms of climacteric women . Since oral PPE did not improve serum E2 and FSH levels , PPE is thought not to ameliorate hormonal balance itself but to improve subjective feelings of climacteric women BACKGROUND S-equol , a metabolite of the soy isoflavone daidzein , has been proposed as having potential for relief of menopausal symptoms . This study compared the efficacy of the natural S-equol supplement , SE5-OH , with isoflavones for relieving hot flashes and other menopausal symptoms . METHODS An 8-week r and omized , double-blind , active comparator trial with SE5-OH was conducted in postmenopausal women ( aged 45 - 65 years ) , who experienced ≥5 hot flashes/day . Participants ( n=102 ) were assigned to one of four treatment groups : 10 ( n=24 ) , 20 ( n=27 ) , or 40 ( n=25 ) mg S-equol/day or soy isoflavones ( n=26 ) . Participants recorded their hot flash frequency and rated their menopause symptom severity . RESULTS Reductions in hot flash frequency at week 8 were similar for all treatment groups . However , based on analyses of the cumulative effect for the 8-week period , 40 mg/day S-equol had a greater reduction of hot flash frequency compared to isoflavones ( p=0.021 ) . A subgroup analysis further indicated that for subjects with > 8 hot flashes/day at baseline , 20 and 40 mg/day S-equol were superior to isoflavones in reducing hot flash frequency ( p=0.045 and p=0.001 , respectively ) . In addition , 10 and 20 mg/day S-equol improved muscle and joint pain score compared with isoflavones ( p=0.003 and p=0.005 , respectively ) . CONCLUSIONS S-equol , 10 mg/day , appears to be as effective as soy isoflavones at reducing hot flash frequency and more effective for relieving muscle and joint pain in postmenopausal women . S-equol , ≥20 mg/day , alleviates hot flashes to a greater extent than soy isoflavones in those women who experience > 8 hot flashes/day Objective The aim of this study was to examine the effectiveness of group cognitive behavioral therapy ( CBT ) and guided self-help CBT in reducing hot flush and night sweat ( HF/NS ) problem rating at 6 and 26 weeks after r and omization . Methods This was a r and omized control trial of 140 women having 10 or more problematic HF/NS a week for at least a month . The primary outcome was HF/NS problem rating ( 1 - 10 ) at 6 weeks after r and omization . Secondary outcomes were physiologically measured HF/NS at 6 weeks ; HF/NS problem rating at 6 weeks ; and frequency , mood ( Women ’s Health Question naire ) , and health-related quality of life ( General Health Survey Short Form–36 ) at 6 and 26 weeks . Intention-to-treat analysis was used , and between-group differences were estimated using linear mixed models . Results Baseline mean ( SD ) HF/NS weekly frequency was 63.15 ( 49.24 ) , and problem rating was 5.87 ( 2.28 ) . Group and self-help CBT both significantly reduced HF/NS problem rating at 6 weeks — group CBT versus no treatment control ( NTC ; adjusted mean difference , 2.12 ; 95 % CI , 1.36 - 2.88 ; P < 0.001 ) and self-help CBT versus NTC ( adjusted mean difference , 2.08 ; 95 % CI , 1.29 - 2.86 ; P < 0.001)— and at 26 weeks — group CBT versus NTC ( adjusted mean difference , 1.33 ; 95 % CI , 0.54 - 2.13 ; P = 0.001 ) and self-help CBT versus NTC ( adjusted mean difference , 1.19 ; 95 % CI , 0.36 - 2.02 ; P = 0.005 ) . Group and self-help CBT significantly reduced night sweat frequency at 6 and 26 weeks . There were improvements in mood and quality of life at 6 weeks and improved emotional and physical functioning for group CBT at 26 weeks . Conclusions These results suggest that CBT delivered in group or self-help format is an effective treatment option for women during the menopause transition and postmenopause with problematic HF/NS PURPOSE To determine the effectiveness of acupuncture for the management of hot flashes in women with breast cancer . PATIENTS AND METHODS We conducted a pragmatic , r and omized controlled trial comparing acupuncture plus enhanced self-care versus enhanced self-care alone . A total of 190 women with breast cancer were r and omly assigned . R and om assignment was performed with stratification for hormonal therapy ; the allocation ratio was 1:1 . Both groups received a booklet with information about climacteric syndrome and its management to be followed for at least 12 weeks . In addition , the acupuncture group received 10 traditional acupuncture treatment sessions involving needling of predefined acupoints . The primary outcome was hot flash score at the end of treatment ( week 12 ) , calculated as the frequency multiplied by the average severity of hot flashes . The secondary outcomes were climacteric symptoms and quality of life , measured by the Greene Climacteric and Menopause Quality of Life scales . Health outcomes were measured for up to 6 months after treatment . Expectation and satisfaction of treatment effect and safety were also evaluated . We used intention-to-treat analyses . RESULTS Of the participants , 105 were r and omly assigned to enhanced self-care and 85 to acupuncture plus enhanced self-care . Acupuncture plus enhanced self-care was associated with a significantly lower hot flash score than enhanced self-care at the end of treatment ( P < .001 ) and at 3- and 6-month post-treatment follow-up visits ( P = .0028 and .001 , respectively ) . Acupuncture was also associated with fewer climacteric symptoms and higher quality of life in the vasomotor , physical , and psychosocial dimensions ( P < .05 ) . CONCLUSION Acupuncture in association with enhanced self-care is an effective integrative intervention for managing hot flashes and improving quality of life in women with breast cancer Menopausal symptoms are a major survivorship issue for patients treated for breast cancer . There are increasing concerns over the use of hormone replacement therapy ( HRT ) in this setting and a growing consumer interest in " natural " therapies . It had been suggested that soy phyto-oestrogens might be beneficial in the treatment of menopausal symptoms . Seventy-two patients with a histologically confirmed pre-existing diagnosis of breast cancer who were having menopausal symptoms were r and omised between 12 weeks of treatment with soy capsules or placebo . Quality of life and menopausal symptom scores were assessed at baseline , 4 , 8 and 12 weeks . There was no statistical difference in menopausal symptom scores or quality of life between the two arms of the study Objective This study is a phase II clinical trial that aims to investigate the dose-response relationship of a Chinese herbal medicine preparation , Dang Gui Buxue Tang ( DBT ) , with short-term menopausal symptoms and quality of life in local postmenopausal women . Methods A r and omized , double-blind , multiple-dose escalation trial was performed in 60 postmenopausal women experiencing severe hot flashes and night sweats . The participants were r and omized to receive DBT preparations at 1.5 , 3.0 , or 6.0 g/day for 12 weeks . The primary outcomes were vasomotor symptoms , Greene Climacteric Scale ( GCS ) score , and Menopause-Specific Quality of Life ( MENQOL ) score . Secondary outcomes included serum hormones and lipids . Results There were between-group differences in psychological/psychosocial ( P = 0.015 , GCS ; P = 0.013 , MENQOL ) and somatic/physical ( P = 0.019 , GCS ; P = 0.037 , MENQOL ) domains , and improvement was significantly greatest ( P < 0.05 ) in the 6.0 g/day dose group . The frequency and severity of hot flashes and night sweats were significantly reduced in the 3.0 g/day ( 14.5%-21.2 % , P < 0.05 , hot flashes ; 28.6%-39.6 % , P < 0.05 , night sweats ) and 6.0 g/day ( 34.9%-37.4.0 % , P < 0.01 , hot flashes ; 10.1%-12.8 % , P < 0.01 , night sweats ) dose groups . The female hormones follicle-stimulating hormone , luteinizing hormone , and 17&bgr;-estradiol , as well as the lipids total cholesterol , triglycerides , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol , were not significantly different within groups and between groups . Conclusions DBT preparations at 6.0 g/day significantly improve physical and psychological scores and significantly reduce vasomotor symptoms from baseline . The treatment was well tolerated , with no serious adverse events noted during the 12-week intervention period . The changes do not affect hormones and lipid profiles Objective We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich ( 80.4 mg/day ) and isoflavone-poor ( 4.4 mg/day ) soy protein isolate treatment in perimenopausal women . Design In this double-blind 24-week study , 69 women were r and omized to treatment : isoflavone-rich soy protein ( n = 24 ) , isoflavone-poor soy protein ( n = 24 ) , or whey protein control ( n = 21 ) . A Menopausal Index was used to assess change in hot flushes and night sweats , as well as other symptoms , at baseline , week 12 , and week 24 . Results Repeated measures analysis of variance indicated no treatment effect on change in hot flush ( p = 0.18 ) and night sweat ( p = 0.92 ) frequency , whereas there was a significant decline in hot flush ( p = 0.0003 ) and night sweat ( p = 0.0007 ) frequency with time in all treatment groups . & khgr;2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point , as well as no treatment effect on frequency or severity of other vasomotor symptoms . At the completion of the study , we found no treatment effect on retrospective perception of frequency , duration , or severity of hot flushes or night sweats . Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms , this indicated either a placebo effect or simply an improvement in symptoms during the study . Conclusion In this study , we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms Objective Hot flashes are a common symptom in breast cancer survivors that can negatively impact quality of life . Preliminary data suggested that magnesium might be used as an effective low-cost treatment of hot flashes with minimal adverse effects . Methods A four-arm , double-blind , placebo-controlled , r and omized trial was conducted . Postmenopausal women with a history of breast cancer and bothersome hot flashes were r and omized into treatment groups of magnesium oxide 800 or 1,200 mg daily or corresponding placebo groups at a 2:2:(1:1 ) ratio . Hot flash frequency and hot flash score ( number × mean severity ) were measured using a vali date d hot flash diary . A 1-week baseline period preceded initiation of study medication . The primary endpoint was intrapatient difference in mean hot flash score between baseline and treatment periods , comparing each magnesium group with the combined placebo groups using a gatekeeping procedure . Results were analyzed using repeated- measures and growth curve models on weekly hot flash scores based on a modified intent-to-treat principle . Results Two hundred eighty-nine women enrolled between December 2011 and March 2013 . Study groups were well balanced for baseline characteristics . Mean hot flash scores , mean hot flash frequencies , and associated changes during the treatment period were similar for each group . An increased incidence of diarrhea and a corresponding lower incidence of constipation were reported in magnesium arms compared with placebo . No statistically significant difference in other toxicities or quality -of-life measures was observed . Conclusions The results of this trial do not support the use of magnesium oxide for hot flashes OBJECTIVES The aim of this study was to evaluate the effects of local thermal therapy with far-infrared rays ( FIR ) on menopausal symptoms and bone mineral density ( BMD ) in postmenopausal women . SUBJECTS AND METHODS A prospect i ve r and omized , controlled trial was conducted in female volunteers from communities in Northern Taiwan . The intervention group ( n=22 ) received local thermal therapy with the help of FIR from an FIR emitter , for approximately 20 minutes per day , twice a week , for 20 sessions . They received the therapy on their backs while lying in a supine position . The control group ( n=21 ) received no treatment . The primary outcome was the change in the Perceived Perimenopausal Disturbances Scale , design ed for the measurement of menopause-related symptoms ( MRS ) before and after completion of treatment in a 10-week period . Secondary outcome parameters included serum levels of estradiol ( E2 ) with osteocalcin ( OC ) , and calcaneal BMD by quantitative ultrasound . RESULTS After 10 weeks of intervention , MRS determined by the scale decreased in mean total scores and mean scores for vasomotor , musculoskeletal , urologic , reproductive , and psychologic domains ( p<0.05 ) , except for reproductive ( sexuality-related ) symptoms . In the control group , mean total scores and scores of each domain had no significant difference between baseline and follow-up examination after 10 weeks . There was no significant difference between the quantitative ultrasound parameters in the calcaneus , serum E2 , and OC levels either at the baseline or in the changes from the baseline between the intervention and control groups of women ( p>0.05 ) . CONCLUSIONS Local thermal therapy with FIR results in a significant reduction of MRS in postmenopausal women . Serum E2 , OC levels , and calcaneal BMD showed no significant changes between the two groups . These results suggest that FIR local thermal therapy may be a potential alternative for the management of postmenopausal symptoms OBJECTIVE : To estimate the effect of the selective serotonin reuptake inhibitor sertraline on hot flush frequency and severity in perimenopausal and postmenopausal women . METHODS : We performed a r and omized , blinded , placebo-controlled trial in women aged 40 to 60 years with 14 or more hot flushes per week ( N=99 ) . Women were r and omly assigned initially to daily oral sertraline ( 50 mg ) or identical placebo for 2 weeks . If no substantial side effects were noted , the dose was increased to two tablets daily ( 100 mg sertraline or placebo ) and continued for an additional 4 weeks . Hot flush frequency and severity were recorded on a daily diary . Hot flush score was calculated as frequency multiplied by severity . Participants also completed question naires addressing quality of life , menopausal symptoms , sleep quality , sexual function , mood , and side effects . RESULTS : After 6 weeks of treatment , hot flush frequency decreased similarly in both the placebo ( 38 % ) and sertraline ( 39 % ) groups ( P=.94 ) . Mean hot flush scores also decreased similarly in both groups ( 41 % and 42 % , respectively , P=.86 ) . Compared with placebo , women in the sertraline group were more likely to report gastrointestinal complaints , dry mouth , and dizziness . Treatment with sertraline also result ed in greater worsening of scores on the Medical Outcomes Study ( MOS ) Short Form 36 st and ardized physical component and the global Female Sexual Function Index . Results were similar in women at least 80 % adherent to study medication . CONCLUSION : Treatment with sertraline did not improve hot flush frequency or severity in generally healthy perimenopausal and postmenopausal women , but was associated with bothersome side effects . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00283192 LEVEL OF EVIDENCE : OBJECTIVE : To investigate the efficacy of micro-dose transdermal estrogen in relieving menopausal vasomotor symptoms . METHODS : A r and omized , double-blind , placebo-controlled , multi-center trial . Healthy postmenopausal women with at least seven moderate or severe hot flushes per day for at least 1 week , or at least 50 per week , applied transdermal patches with a nominal delivery of 0.023 mg/d 17β-estradiol and 0.0075 mg/d levonorgestrel ( low-dose E2/levonorgestrel ; n=145 ) , 0.014 mg/d E2 ( micro-dose ; n=147 ) , or placebo ( n=133 ) for 12 weeks . The co primary efficacy variables were the mean changes from baseline in frequency and severity of moderate and severe hot flushes at the week 4 and 12 endpoints . RESULTS : At the week 12 endpoint , mean weekly frequencies of moderate and severe hot flushes were significantly reduced compared with placebo with low-dose E2/levonorgestrel ( −51.80 ; P<.001 ) and micro-dose E2 ( −38.46 ; P<.001 ) . Severity scores were also significantly reduced with both treatments compared with placebo . At week 12 endpoint , 41.3 % of women receiving micro-dose E2 were treatment responders ( 75 % or more reduction from baseline in hot flush frequency ; P=.003 compared with 24.2 % placebo ) . In this group , the mean reduction in moderate and severe hot flushes from baseline was approximately 50 % after 2 , 70 % after 4 , 90 % after 8 , and 95 % after 12 weeks . There were no differences between active treatments and placebo regarding adverse events . CONCLUSION : Micro-dose E2 ( 0.014 mg/d ) was clinical ly and statistically significantly more effective than placebo in reducing the number of moderate and severe hot flushes , with a 41 % responder rate , supporting the concept of the lowest effective dose . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00206622 LEVEL OF EVIDENCE : Objective : Women diagnosed as having breast cancer may experience difficulties with posttreatment effects such as menopausal symptoms . The aims of this pilot study were to ( 1 ) evaluate the impact of a multimodal lifestyle program on reducing menopausal symptoms in women with breast cancer and ( 2 ) examine the impact of the program on health-related quality of life ( HRQoL ) and adherence to lifestyle recommendations . Methods : Overall , 55 women aged 45 to 60 years with one moderate to severe menopausal symptom and a history of breast cancer were r and omized into an intervention group ( n = 26 ) or a control group ( n = 29 ) . Women in the intervention group received a lifestyle intervention ( The Pink Women 's Wellness Program ) that included clinical consultations and a tailored health education program . Measurements of menopausal symptoms ( Greene Climacteric Scale ) , HRQoL ( SF-12 and Functional Assessment of Cancer Therapy — Breast ) , and modifiable lifestyle factors ( food intake , physical activity , smoking and alcohol use , and sleep disturbance ) were taken at baseline and 12 weeks . Results : Women in the intervention group reported clinical ly significant reductions in many menopausal symptoms , specifically somatic symptoms ( d = 0.52 ) , vasomotor symptoms ( d = 0.55 ) , sexual dysfunction ( d = 0.65 ) , and overall menopausal symptoms ( d = 0.54 ) , at 12 weeks compared with the control group ( d = 0.03 , d = 0.24 , d = 0.18 , and d = 0.05 , respectively ) . Women in the intervention group reported improvements in Functional Assessment of Cancer Therapy — Breast subscale scores , physical well-being and functional well-being , and Functional Assessment of Cancer Therapy — General total scores ( intervention group : d = 0.54 , d = 0.50 , and d = 0.48 , respectively ; control group : d = 0.22 , d = 0.11 , and d = 0.05 , respectively ) . Conclusions : The Pink Women 's Wellness Program is effective in decreasing menopausal symptoms , thus improving HRQoL. This being a pilot study , further research is recommended to investigate the benefits of combining nonpharmacological interventions for women with breast cancer to reduce their treatment-related menopausal symptoms Objective To compare the efficacy of different doses of 17β-estradiol ( E2 ) for relief of vasomotor symptoms in menopausal women . Methods This was a r and omized , double-masked , placebo-controlled , 12-week study in which 333 menopausal women with moderate or severe hot flushes were assigned to treatment with 0.25 mg , 0.5 mg , 1 mg , or 2 mg oral micronized 17β-E2 , or placebo . The number and severity of hot flushes were recorded daily . Results There was a significant linear correlation between increased dosage of 17β-E2 and decreased moderate to severe hot flushes per week ( P < .001 ) . Rapid reduction in moderate to severe hot flushes was only achieved with 1 and 2 mg , showing a significant difference from placebo at week 4 ( P < .05 ) . At week 4 , half the women on placebo had reduced moderate to severe hot flushes of at least 52 % ; the corresponding figures were 56 % , 69 % , 86 % , and 91 % for 0.25 , 0.5 , 1 , and 2 mg , respectively . At week 12 , all doses except 0.25 mg were significantly better than placebo for reducing moderate to severe hot flushes ( P < .001 ) . Although there were no significant differences , twice as many women in the 2-mg group discontinued treatment due to adverse events , compared with the placebo group . Conclusion Oral micronized 17β-E2 showed a dose-response effect for reducing moderate and severe hot flushes in menopausal women . 17β-E2 1 mg appeared to be the most useful initial dose PURPOSE Vasomotor hot flashes are a common problem in menopausal women . Given concerns regarding estrogen and /or combined hormonal therapy , other treatment options are desired . Prior trials have confirmed that progestational agents and newer antidepressants effectively reduce hot flashes . This current trial compared a single intramuscular dose of medroxyprogesterone acetate ( MPA ) , depot preparation , versus daily oral venlafaxine as treatment for hot flashes . METHODS Women with bothersome hot flashes were entered onto this trial , were r and omly assigned to treatment , and then had a baseline week where hot flash scores were recorded without treatment . They were then treated and observed for 6 weeks ; daily diaries were used to measure hot flash frequencies and severities . There were 109 patients per each arm r and omly assigned to receive MPA 400 mg intramuscularly for a single dose versus venlafaxine 37.5 mg per day for a week , then 75 mg per day . RESULTS During the sixth week after r and om assignment , hot flash scores were reduced by 55 % in the venlafaxine arm versus 79 % in the MPA arm ( P < .0001 ) . In an intention-to-treat analysis , 46 % of venlafaxine patients ( 50 of 109 ) compared with 74 % of the MPA patients ( 81 of 109 ) had a decrease in hot flashes by more than 50 % from baseline ( P < .0001 ) . Less toxicity was reported in the MPA arm . CONCLUSION A single MPA dose seems to be well tolerated and more effectively reduces hot flashes than does venlafaxine Objective : To investigate the effects of a novel dietary supplement containing soy isoflavones and Actaea racemosa Linnaeus ( formerly called Cimicifuga racemosa L. ) on climacteric symptoms in healthy perimenopausal women . Design : In a multicenter , r and omized , placebo-controlled , double-blind study , 124 women experiencing at least five vasomotor symptoms every 24 hours were r and omized to receive daily either a phytoestrogen-containing supplement ( n = 60 ) or placebo ( n = 64 ) for 12 weeks . The modified Kupperman Index and Greene Climacteric Scale , a visual analogue scale design ed to measure quality of life and the daily number and severity of hot flushes , was used in the screening period and in weeks 6 and 12 . Changes in these scores from baseline were calculated . Results : At weeks 6 and 12 , all scores in both groups had improved compared with baseline , though the overall difference in scores between the groups was not statistically significant . Conclusion : The supplement containing soy isoflavones and A racemosa L. had no statistically significant effect on climacteric symptoms in perimenopausal women experiencing at least five vasomotor symptoms per day OBJECTIVE : A study was conducted to evaluate the safety and efficacy of 3 different doses of synthetic conjugated estrogens B , a new plant-derived 10-component conjugated estrogens product , for the treatment of menopausal vasomotor symptoms . METHODS : This was a r and omized , double-blind , placebo-controlled trial . Highly symptomatic menopausal women ( N = 281 ) received 12 weeks of a once-daily oral treatment with 0.3 mg , 0.625 mg , or 1.25 mg of 10-component synthetic conjugated estrogen or placebo . Patients recorded the daily frequency and severity of hot flushes . Statistical analyses compared results at weeks 4 , 8 , and 12 with baseline values . RESULTS : Statistically significant reductions ( P < .05 ) in the frequency and severity of vasomotor symptoms were observed for all 3 dosage strengths of 10-component synthetic conjugated estrogen compared with placebo . The most commonly reported adverse events in all treatment groups were headaches . No difference in the incidence of treatment-related adverse events was seen between placebo and 10-component synthetic conjugated estrogen groups . CONCLUSION : The 0.3-mg , 0.625-mg and 1.25-mg dose strengths of 10-component synthetic conjugated estrogen significantly reduced the frequency and severity of vasomotor symptoms compared with placebo , and were well tolerated during this 12-week study . LEVEL OF EVIDENCE : OBJECTIVE : To compare the efficacy of gabapentin , estrogen , and placebo in the treatment of hot flushes . METHODS : We performed a r and omized , double-blind , placebo-controlled trial of 60 postmenopausal women to assess the efficacy of estrogen and gabapentin in the treatment of moderate-to-severe hot flushes . Participants were r and omly assigned to receive either 0.625 mg/d of conjugated estrogens ( n = 20 ) , placebo ( n = 20 ) , or gabapentin titrated to 2,400 mg/d ( n = 20 ) for 12 weeks . Participants recorded frequency and severity of baseline hot flushes on a hot flush diary for 2 weeks before r and omization and for 12 weeks after r and omization . The primary outcome measure was the weekly hot flush composite score , which takes into account both severity and frequency of hot flushes . Secondary outcome measures were differences in pre- and posttreatment scores pertaining to depression ( Zung Depression Scale ) and other climacteric symptoms ( Greene Climacteric Scale ) . RESULTS : Intention-to-treat analysis showed that the reduction in the hot flush composite score for both estrogen ( 72 % , P = .016 ) and gabapentin ( 71 % , P = .004 ) was greater than the reduction associated with placebo ( 54 % ) at the conclusion of the 12th week . The extent of reduction in hot flush composite score , however , was not significantly different between estrogen and gabapentin ( P = .63 ) . No differences were seen between groups in the Zung Depression Scale , or in any of the Greene Climacteric subscales except for the Somatic Symptom cluster , which was significantly greater in the gabapentin arm than in the placebo arm . Despite a lack of group differences in adverse events , the Headache , Dizziness , and Disorientation cluster appeared with greater frequency in the gabapentin group . Estimation of the number needed to harm in this cluster suggests that these symptoms may occur with every fourth patient treated with gabapentin . CONCLUSION : Despite the small scale of this study , gabapentin appears to be as effective as estrogen in the treatment of postmenopausal hot flushes . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , NCT 00276081 . LEVEL OF EVIDENCE : Objective Many complementary or alternative medicines are being used for the treatment of menopausal symptoms but most have not been properly tested for efficacy or for safety . This study examined the effect of a Chinese herbal preparation ( Dang Gui Buxue Tang ) on menopausal symptoms in Hong Kong Chinese women . Methods A 6-month r and omized , double-blind , placebo-controlled study of the effect of Dang Gui Buxue Tang ( a 1 : 5 combination of Dang Gui ( Angelicae sinensis ) and Huang Qi ( Astragalus membranaceus ) ) on acute menopausal symptoms . A total of 103 symptomatic women were enrolled . Three failed to meet inclusion criteria , leaving 50 subjects for inclusion in each group . Results Overall , mild hot flushes were reported more frequently than either moderate or severe flushes . In analysis by severity of flushes , there was a significant reduction in the number of mild hot flushes per month in the treatment group but not in the placebo group ( from 18.9 ± 23.5 at baseline to 8.6 ± 17.1 at 6 months in the treatment group ( p < 0.01 ) and from 26.0 ± 43.5 to 12.4 ± 17.6 in the placebo group ( p = 0.062 ) ) . For moderate flushes , there was a significant reduction in the placebo group compared with the treatment group ( from 18.9 ± 28.7 at baseline to 11.1 ± 29.9 at 6 months in the placebo group ( p < 0.05 ) and from 10.5 ± 22.3 to 6.0 ± 16.0 in the treatment group ( p = 0.107 ) ) . There was no significant change in either treatment or placebo groups in the reporting of severe hot flushes . Episodes of night sweats decreased significantly in the placebo but not in the treatment group ( from 6.8 ± 10.0 at baseline to 1.9 ± 5.7 at 6 months in the placebo group ( p < 0.05 ) and from 5.4 ± 8.9 to 3.2 ± 8.5 in the treatment group ( p = 0.471 ) ) . In the vasomotor domain of the Menopause Specific Quality of Life , there was a significant reduction in scoring in the placebo group ( from 2.8 ± 1.6 to 1.7 ± 1.3 , p < 0.01 ) but not in the treatment group ( from 2.8 ± 2.1 to 2.3 ± 1.6 , p = 0.247 ) . Conclusions This study found overall no significant difference between Dang Gui Buxue Tang and placebo in the treatment of vasomotor symptoms in Hong Kong Chinese women . The frequency of mild , moderate and severe hot flushes decreased in both treatment and placebo groups , but Dang Gui Buxue Tang was statistically superior to placebo only in the treatment of mild hot flushes . There were no serious adverse events attributable to treatment during the study period Objective This study aim ed to evaluate the effectiveness and safety of a Chinese herbal medicine preparation , Jiawei Qing’e Fang ( JQF ) , on menopausal symptoms in perimenopausal women . Methods A r and omized double-blind placebo-controlled trial was performed over 12 weeks in 72 perimenopausal women who reported 14 or more hot flashes per week . The participants were r and omly allocated to receive JQF or placebo for 8 weeks . Posttreatment follow-up was performed 4 weeks after intervention . The primary outcome was the Menopause-Specific Quality of Life . Secondary outcomes included hot flash and plasma lipids . Results There was greater improvement in hot flash score in the JQF group compared with the placebo group , and the difference between the two groups was statistically significant ( P = 0.048 ) . There were between-group differences in vasomotor ( P = 0.011 ) and physical ( P = 0.034 ) domains . The triglyceride ( TG ) level in the JQF group showed a significant reduction ( P = 0.036 ) in women with a baseline TG greater than 150 mg/dL ( 1.7 mmol/L ) . Conclusions The Chinese herbal medicine preparation JQF was found to be superior to placebo in reducing hot flashes and improving menopausal symptoms in the vasomotor and physical aspects and might have a potential benefit in reducing TG levels . The herbal medicine preparation was well tolerated , with no serious adverse events noted during the study period Objective The aim of this study was to assess the 12-week efficacy of desvenlafaxine in treating moderate to severe vasomotor symptoms and the clinical relevance of improvements in postmenopausal women experiencing 50 or more moderate to severe hot flashes per week . Methods Participants were r and omized to placebo or desvenlafaxine 100 mg/day in the 12-week efficacy sub study of a year-long , multicenter , parallel-group , double-blind study . Co primary outcomes were changes from baseline in the daily number and severity of hot flashes on weeks 4 and 12 . The percentage of women achieving the minimal clinical ly important difference ( MCID ) in the number of hot flashes on week 12 was determined . Results The efficacy sub study modified intent-to-treat population included 365 women ( desvenlafaxine , n = 184 ; placebo , n = 181 ) . Desvenlafaxine 100 mg/day significantly reduced the number and severity of hot flashes versus placebo on week 4 ( P < 0.001 ) and week 12 ( P < 0.001 ) . On week 12 , desvenlafaxine reduced the number of moderate and severe hot flashes by 7.3 ( 62 % ) per day ( placebo , −4.5 [ 38 % ] per day ) and the severity score by 0.59 ( 25 % ) per day ( placebo , −0.28 [ 12 % ] per day ) . MCID — a reduction of 5.35 moderate and severe hot flashes per day — was achieved by 64 % of desvenlafaxine-treated women ( placebo , 41 % ; P < 0.001 ) . In all , 17.2 % ( 67/390 ) of participants discontinued , 10.0 % ( 20/200 ) of participants taking desvenlafaxine and 3.7 % ( 7/190 ) of participants taking placebo discontinued because of adverse events ( P = 0.016 ) , and 2.5 % ( 5/200 ) of participants taking desvenlafaxine and 8.4 % ( 16/190 ) of participants taking placebo discontinued because of lack of efficacy ( P = 0.012 ) . Conclusions Postmenopausal women with moderate to severe hot flashes who are treated with desvenlafaxine achieve rapid symptom reduction that is clinical ly relevant based on MCID OBJECTIVES To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day ( Estraderm MX 50 ) in postmenopausal women with moderate to severe postmenopausal symptoms . METHODS A multicenter , double-blind , r and omized , between-patient , placebo controlled trial in 109 postmenopausal women was carried out . Patches were applied twice weekly for 12 weeks . Patients were assessed at 4 , 8 and 12 weeks of treatment . The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes ( including night sweats ) per 24 h during the last 2 weeks of treatment . Other variables included Kupperman Index , local and systemic tolerability . Plasma concentrations of estradiol ( E2 ) , estrone ( E1 ) and estrone sulfate ( E1S ) were determined before and after treatment . RESULTS Estraderm MX was significantly superior to placebo ( P < 0.001 ) in reducing mean number of moderate to severe hot flushes ( including night sweats ) per 24 h after 4 , 8 and 12 weeks of treatment . The estimate of treatment group differences after 12 weeks was 4.2 hot flushes ( 95 % confidence interval : 2.6 - 5.8 ) . Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo ( P < 0.001 ) . Estraderm MX induced increases in mean E2 , E1 and E1S plasma levels as expected ( E2 : baseline 2.7 pg/ml , 12 weeks 38.9 pg/ml ; E1 : baseline 18.8 pg/ml , 12 weeks 41.6 pg/ml ; E1S : baseline 235.6 pg/ml , 12 weeks 765.1 pg/ml ) . Overall rates of adverse experiences were similar for Estraderm MX and placebo . The number of patients reporting skin irritation was low and similar in both groups . CONCLUSIONS Estraderm MX 50 , a new matrix patch , offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day Objective : The aim of this pilot double-blind , r and omized clinical trial , which initially targeted breast cancer survivors , was to obtain preliminary evidence of the effect of Hypericum perforatum extract ( St. John 's wort extract ) compared with placebo on symptoms and quality of life of symptomatic perimenopausal women . We also assessed practical difficulties in recruiting women to such a trial . Methods : Symptomatic perimenopausal women aged 40 to 65 years who experience hot flashes ( three or more per day , Heart and Estrogen/Progestin Replacement Study scale ) were r and omly assigned to receive ethanolic St. John 's wort extract ( 900 mg TID ) or placebo . The women were asked to keep a daily diary during the week before r and omization and during the week before the 3-month follow-up ( primary outcome ) to record hot flash frequency and intensity . A hot flash score ( frequency × severity ) was calculated . The Menopause-Specific Quality of Life question naire was used to assess menopause-specific quality of life . Results : Forty-seven women were r and omized . After 12 weeks of treatment , a nonsignificant difference favoring the St. John 's wort group was observed in the daily hot flash frequency ( St. John 's wort , −2.3 ± 3.6 ; placebo , −1.0 ± 2.2 ; P = 0.11 ) and the hot flash score ( −3.8 ± 8.3 and −1.8 ± 6.5 , respectively ; P = 0.10 ) . After 3 months of treatment , compared with the placebo group , women in the St. John 's wort group reported significantly better menopause-specific quality of life ( P = 0.01 ) and significantly fewer sleep problems ( P = 0.05 ) . Conclusions : Hypericum perforatum may improve quality of life in ways that are important to symptomatic perimenopausal women , but these results need to be confirmed by a larger clinical trial Objective : The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1 % ( Divigel , a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel ) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause . Design : A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1 % at doses of 1.0 , 0.5 , and 0.25 mg/day , with estimated daily deliveries of 0.027 , 0.009 , and 0.003 mg of estradiol , respectively . Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms . Change from baseline in the signs of vulvar and vaginal atrophy ( vaginal pH and percentage of superficial cells ) was also assessed . Results : Treatment with estradiol gel 0.1 % showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment . Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1 % compared with placebo . Conclusions : Low-dose transdermal estradiol gel 0.1 % is an effective treatment for relief of vasomotor symptoms , as well as signs of vulvar and vaginal atrophy , associated with menopause . Estradiol gel 0.1 % offers multiple dosing options to individualize patient therapy , including the lowest available effective dose ( 0.25 mg estradiol , delivering 0.003 mg/d estradiol ) to treat the vasomotor symptoms of menopause Two-hundred and five ( 205 ) menopausal women with moderate to severe vasomotor symptoms , aged 39 - 64 years , were r and omized from 20 clinical centers . After a 4-week treatment-free period , each woman received a cyclical regimen ( 25 days of a 4-week cycle ) of Menorest 50 , a new matrix-type transdermal estradiol system or Estraderm TTS 50 , a marketed reservoir-type transdermal estradiol system twice weekly for 12 weeks . An oral progestin was also given for 10 days each cycle . The objectives were to compare local and systemic tolerability and efficacy in the treatment of menopausal symptoms . One-hundred and ninety-four [ 194 ] patients ( 96 and 98 patients in the Menorest 50 and the reservoir transdermal patch groups , respectively ) were considered in the intent-to-treat population and 204 ( 102 in each group ) in the safety population . The two treatment groups were comparable with regard to the demographic data and menopausal status . The primary efficacy criteria were the comparison between Menorest 50 and the reservoir transdermal patch in erythema and pruritus at application sites and the difference between the treatment groups in the mean number of hot flushes per day at week 12 , adjusted for baseline . A statistically significant reduction in the mean number of hot flushes was observed in each group compared with baseline , with a decrease from 6.5 at baseline to 0.3 at 12 weeks and 6.4 to 0.4 in the Menorest 50 and reservoir transdermal patch groups respectively ; there was no statistically significant difference between the two groups during the 12-week treatment . The severity score of menopausal symptoms was also dramatically improved in each of the two treatment groups . There were no statistically significant differences in the mean plasma estradiol concentrations and mean estradiol to estrone ratio ( > 1.0 ) in both groups after 10 weeks of therapy . A similar number of adverse events was observed in both groups . Menorest 50 showed better local tolerability than the reservoir transdermal patch with a lower incidence of topical adverse events , erythema and pruritus . In summary , Menorest 50 was as effective as the reservoir transdermal patch in reducing the mean number of hot flushes , and improving the severity of other menopausal symptoms , including vasomotor , psychiatric and urogenital symptoms Objective : The aim of the study was to evaluate the short and long-term effects of acupuncture on vasomotor symptoms ( VMS ) and quality of life-related measures . Methods : A total of 209 perimenopausal and postmenopausal women aged 45 to 60 years , experiencing four or more VMS per day , were recruited from the community and r and omized to receive up to 20 acupuncture treatments within the first 6 months ( acupuncture group ) or the second 6 months ( waitlist control group ) of the 12-month study period . The primary outcome was mean daily frequency of VMS . Secondary outcomes were VMS interference with daily life , sleep quality , depressive symptoms , somatic and other symptoms , anxiety , and quality of life . Results : The VMS frequency declined by 36.7 % at 6 months in the acupuncture group and increased by 6.0 % in the control group ( P < 0.001 for between-group comparison ) . At 12 months , the reduction from baseline in the acupuncture group was 29.4 % ( P < 0.001 for within-group comparison from baseline to 12 months ) , suggesting that the reduction was largely maintained after treatment . Statistically significant clinical improvement was observed after three acupuncture treatments , and maximal clinical effects occurred after a median of eight treatments . Persistent improvements were seen in many quality of life-related outcomes in the acupuncture group relative to the control group . Conclusions : We found that a course of acupuncture treatments was associated with significant reduction in VMS , and several quality -of-life measures , compared with no acupuncture , and that clinical benefit persisted for at least 6 months beyond the end of treatment Objective : The aim of the study was to assess the efficacy and safety of RAD1901 , an oral estrogen receptor lig and , for the treatment of moderate-to-severe vasomotor symptoms of menopause . Methods : This was a r and omized , placebo-controlled , double-blind , dose-ranging , proof-of-concept trial . Postmenopausal women with a minimum of 7 moderate-to-severe , diary-reported hot flashes per day , or 50 per week , were r and omized to one of five blinded dose groups ( 0 [ placebo ] , 10 , 25 , 50 , or 100 mg RAD1901 daily for 28 d ) . Efficacy endpoints included frequency and severity of hot flashes over 4 weeks of treatment . Results : One hundred participants were r and omized across the five treatment regimens . The frequency of moderate-to-severe hot flashes decreased in all groups over the treatment period ( mean percent change from baseline at 4 wk , −54.1 % , −77.2 % , −51.8 % , −53.8 % , and −67.0 % for placebo , 10 , 25 , 50 , and 100 mg groups ) . The response in the 10 mg group was significantly different from placebo at 4 weeks ( P = 0.024 ) . No other dose group was significantly different from placebo . There were no statistically significant differences in severity of hot flashes between placebo and any dose group . Treatment was well tolerated ; most treatment-emergent adverse events were mild to moderate in severity . Conclusions : Daily treatment with 10 mg RAD1901 over 4 weeks result ed in a statistically significant reduction in the frequency of moderate-to-severe hot flashes compared with placebo , with an acceptable safety profile . Further clinical trials are warranted to investigate RAD1901 's utility as a potential treatment for vasomotor symptoms Objective Dietary supplements containing soy or isoflavones are widely used as alternatives to hormone therapy . However , their efficacy is still inconclusive , and limited data on equol producers are available . The aim of this study was to examine the effect of whole soy ( soy flour ) or purified daidzein ( one major soy isoflavone and the precursor of equol ) on menopausal symptoms in equol-producing postmenopausal women , a population most likely to benefit from soy intervention . Methods This is a 6-month parallel-group , double-blind , r and omized , placebo-controlled trial . Two hundred seventy equol-producing prehypertensive Chinese postmenopausal women were r and omized to one of three treatment groups : 40 g of soy flour ( whole soy group ) , 40 g of low-fat milk powder + 63 mg of daidzein ( daidzein group ) , or 40 g of low-fat milk powder ( placebo group ) daily , each given as a solid beverage for 6 months . Changes in menopausal symptoms were assessed by a vali date d and structured symptom checklist at baseline and 6 months . Results Two hundred fifty-three participants completed the study according to protocol . Urinary isoflavones indicated good compliance with the interventions . Baseline menopausal symptoms were comparable among the three study groups . Intention-to-treat analysis indicated that there was no significant difference in the 6-month changes or percent changes in the total number of menopausal symptoms , in the five dimensions of symptoms , and in the frequencies of individual symptoms among the three treatment groups . Conclusions Whole soy and purified daidzein have no significant effect on alleviation of menopausal symptoms among equol-producing postmenopausal women with prehypertension Objective : The aim of this study was to assess the safety and efficacy of bazedoxifene (BZA)/conjugated estrogens ( CE ) treating moderate to severe vasomotor symptoms in the Selective Estrogen Menopause and Response to Therapy 2 trial . Methods : This was an outpatient , multicenter , double-blind , r and omized , placebo-controlled , phase 3 study conducted in the United States . Healthy postmenopausal women ( N = 332 ; aged 40 - 65 y ) with moderate to severe hot flushes ( ≥7/d or 50/wk ) were r and omized to BZA 20 mg/CE 0.45 mg , BZA 20 mg/CE 0.625 mg , or placebo once daily for 12 weeks . Changes from baseline in the average daily number of moderate and severe hot flushes and daily severity score were assessed at weeks 4 and 12 ; adverse events were recorded . Results : BZA/CE significantly reduced the number and severity of hot flushes at weeks 4 and 12 ( P < 0.001 ) . At week 12 , BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg reduced hot flushes from baseline by 74 % ( 10.3 hot flushes [ baseline ] vs 2.8 [ week 12 ] ) and 80 % ( 10.4 vs 2.4 ) , respectively , compared with 51 % ( 10.5 vs 5.4 ) for placebo . More participants at week 12 had at least a 75 % decrease in hot flushes with BZA 20 mg/CE 0.45 mg ( 61 % ) and BZA 20 mg/CE 0.625 mg ( 73 % ) versus placebo ( 27 % ; P < 0.001 ) . The safety profile was similar between BZA/CE and placebo , and no unexpected safety findings were reported . Conclusions : BZA 20 mg paired with CE 0.45 or 0.625 mg is effective , with short-term safety , for treating vasomotor symptoms in postmenopausal women Objective : The aim of this study was to analyze the effect of participation in a mindfulness training program ( mindfulness-based stress reduction , [ MBSR ] ) on the degree of bother from hot flashes and night sweats . Methods : This study was a r and omized trial of 110 late perimenopausal and early postmenopausal women experiencing an average of 5 or more moderate or severe hot flashes ( including night sweats)/day . A wait-list control ( WLC ) was used with 3-month postintervention follow-up . The main outcome was the degree of bother from hot flashes and night sweats in the previous 24 hours . Secondary measures were hot flash intensity , quality of life , insomnia , anxiety , and perceived stress . Results : Baseline average ( SD ) hot flash frequency was 7.87 ( 3.44 ) and 2.81 ( 1.76 ) night sweats/day . Mean ( SD ) bothersomeness score was 3.18 ( 0.55 ; " moderately bothered/extremely bothered " ) . All analyses were intention to treat and were controlled for baseline values . Within-woman changes in bother from hot flashes differed significantly by treatment arm ( week × treatment arm interaction , P = 0.042 ) . At completion of the intervention , bother in the MBSR arm decreased on average by 14.77 % versus 6.79 % for WLC . At 20 weeks , total reduction in bother for MBSR was 21.62 % and 10.50 % for WLC . Baseline-adjusted changes in hot flash intensity did not differ between treatment arms ( week × treatment arm interaction , P = 0.692 ) . The MBSR arm made clinical ly significant improvements in quality of life ( P = 0.022 ) , subjective sleep quality ( P = 0.009 ) , anxiety ( P = 0.005 ) , and perceived stress ( P = 0.001 ) . Improvements were maintained 3 months postintervention . Conclusions : Our data suggest that MBSR may be a clinical ly significant re source in reducing the degree of bother and distress women experience from hot flashes and night sweats Background . Gabapentin ( GPT ) , a widely used drug in neurology , has been proposed as a non-hormonal option for the management of hot flushes in menopausal women with contraindications for estrogen therapy . Objective . To compare GPT versus low-dose transdermal estradiol ( E2 ) for treating post-menopausal women with moderate to very severe hot flushes . Methods . A total of 45 post-menopausal women with moderate to very severe hot flushes were prospect ively and single-blinded r and omised to receive oral GPT 600 mg/night or transdermal 25 μg/day E2 per week . Hot flush intensity and frequency were assessed with the Menopause Rating Scale and a numeric scale respectively at baseline and at 1 , 4 and 8 weeks . Side effects were also assessed . Results . Hot flush intensity and frequency significantly decreased for both groups at 1 , 4 and 8 weeks of treatment as compared to baseline ; however , this decrease was statistically more evident for the E2 group . Although the percentage of hot flush intensity and frequency reduction at the end of the treatment was higher for E2 , this was not statistically significant ( 68.2 % vs. 60.6 % for intensity and 70.1 % vs. 58.9 % for frequency , respectively , p > 0.05 , NS ) . Encountered side effects included : drowsiness , dizziness , fatigue ( GPT group ) and mastodynia , vaginal spotting and a local allergic reaction ( E2 group ) . Compliance to treatment was 95.6 % ( GPT group ) as compared to 90.9 % for the E2 group . Conclusion . Despite statistical significant differences , from a clinical point of view oral GPT 600 mg was as effective as low-dose transdermal E2 in controlling moderate to severe hot flushes in post-menopausal women , and should be recommended as an alternative option in those with contraindications to estrogen therapy . More research is warranted in this regard ABSTRACT Objective Estrogen is the most effective treatment for vasomotor symptoms . Given its potential risks , herbal preparations and nutritional supplements have been developed as alternative remedies . The main aim of this double-blind , r and omized , placebo-controlled trial was to assess any impact of a nutritional supplement containing 12 vitamins and nine minerals on the frequency and severity of hot flushes in postmenopausal women over a 3-month period . Subjects and methods Ninety-one postmenopausal women were r and omized to either the placebo ( n = 45 ) or the treatment arm ( n = 46 ) . Seventy out of the 91 women completed the study ( 36 from the treatment group and 34 from the placebo group ) . At baseline and the 14-week post-intervention assessment s , study participants completed question naires on the frequency and severity of hot flushes and night sweats , the Profile of Mood State question naire , the World Health Organization Quality of Life Question naire , the National Adult Reading Test and the Rey Auditory-Verbal Learning Test . Between assessment s , the women also completed hot flush diaries . Results There was a significant decrease ( p < 0.01 ) in the number ( ±st and ard error of the mean ) of hot flushes experienced per week for treatment ( pre 31.3 ± 4.7 ; post 23.1 ± 4.8 ) and placebo groups ( pre 28.1 ± 4.7 ; post 17.3 ± 4.0 ) . A significant decrease ( p < 0.001 ) in the number of night sweats experienced per week was also observed in the treatment ( pre 6.1 ± 1.0 ; post 4.2 ± 0.7 ) and placebo groups ( pre 5.9 ± 0.7 ; post 3.7 ± 0.7 ) . Conclusions This study demonstrates a significant placebo effect on hot flushes and night sweats , as consistent with other studies . The micronutrient supplement containing 21 vitamins and minerals was not superior over placebo in effects on hot flushes and night sweat experiences |
2,196 | 19,818,030 | RESULTS We found no evidence that directly linked the timing , frequency , or method of pain assessment with outcomes or safety in medical in patients .
There is good evidence that treating abdominal pain does not compromise timely diagnosis and treatment of the surgical abdomen .
Pain management teams and other systemwide interventions improve assessment and use of analgesics , but do not clearly affect pain outcomes .
The safety and effectiveness of PCA in medical patients have not been studied .
There is weak evidence that most cognitively impaired individuals can underst and at least one self- assessment measure .
Almost no evidence is available to guide management of pain in delirium .
Pain is a prevalent problem for medical in patients . | OBJECTIVE To review the literature addressing effective care for acute pain in in patients on medical wards . | Background : The administration of analgesics to patients with acute abdominal pain due to acute appendicitis is controversial . A study was undertaken to assess the analgesic effect of morphine in patients with acute appendicitis . Methods : A r and omised double-blind clinical trial was conducted in Sina hospital , a general teaching hospital , from January 2004 to March 2005 . Patients scheduled for appendectomy were r and omised to receive 0.1 mg/kg morphine sulfate or saline ( 0.9 % ) to a maximum dose of 10 mg over a 5 min period . Patients were examined by surgeons not involved in their care before and after drug administration and their pain intensity and signs were recorded at each visit . The physicians were also asked to indicate their own treatment plan . The main outcome measures were pain intensity using a visual analogue scale ( VAS ) and signs of acute appendicitis . A favourable reduction in VAS score was defined as a change of > 13 mm . Results : Of the 71 patients enrolled in the study , 35 were allocated to receive morphine and 36 to receive placebo . One patient left the hospital before receiving morphine . No significant differences were seen between the two groups with regard to age , sex and initial VAS score . A more favourable change in VAS score was reported in the morphine group with a significantly greater reduction in the median VAS score than in the placebo group . Morphine administration did not cause significant changes in patients ’ signs or in the physicians ’ plans or diagnoses . No adverse events were seen in either group . Conclusion : Morphine can reduce pain in patients with acute appendicitis without affecting diagnostic accuracy . Trial registration number : NCT00477061 BACKGROUND Acute and chronic pain is common in hospitalized demented elderly people , yet there are limited data about the performance of pain assessment tools in this population . The aim of this study was to evaluate the feasibility and reliability of four pain self- assessment scales in this population and compare their performance to an observational pain rating scale . METHODS Our prospect i ve clinical study was conducted in an acute-care and intermediate-care geriatric hospital on 160 consecutive inpatient referrals to the dementia consultation who met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for dementia . Exclusion criteria were delirium , terminal care , and severe sensory impairment . Four unidimensional self- assessment tools -- the verbal , horizontal visual , vertical visual , and faces pain scales -- were administered in r and omized order to mild , moderate , and severely demented patients . An observational pain rating scale was independently completed by the nursing team . RESULTS Only 12 % of the 160 patients ( mean age 85 years , 71 % women ) understood no scale . Respectively , 97 % , 90 % , and 40 % of patients with mild , moderate , and severe dementia understood at least one scale ( p < .05 ) . There was a nonsignificant trend toward poorer comprehension of the faces scale . Test-retest reliability was high for all four self- assessment scales , and the correlation between these scales was very strong ( Spearman 's r(s ) = 0.81 - 0.95 ; p < .001 ) . Observational rating correlated moderately with self- assessment and tended to underestimate pain intensity ( r(s ) = 0.31 - 0.40 ; p < .05 ) . CONCLUSIONS Self- assessment pain scales can be used reliably in the vast majority of older hospitalized patients with mild to moderate dementia and in nearly half of those with severe dementia . Observational pain rating scales correlate only moderately with self- assessment and should be reserved for those few patients who have demonstrated that they can not complete a self- assessment To determine whether reliable and valid rankings of pain and discomfort result ing from hospital procedures encountered by advanced dementia patients could be developed from interviews with cognitively intact adults , rankings of pain and discomfort result ing from 16 common procedures were obtained from two sample s of hospitalized , nondemented adults using ten- ( N = 100 ) and five- ( N = 35 ) point numeric rating scales ( NRS ) . Reliability was assessed by having 30 additional subjects complete ten-point NRS representing the ten most frequent procedures in a re-arranged order . By repeated measure analysis of variance , the scales discriminated between procedures ( F = 35.1 , P < 0.001 ) . Subjects could discriminate between pain and discomfort ( F = 21.6 , P < 0.001 ) . The five-point NRS exhibited better subject discrimination between experiences . Reliability was also acceptable . A five-point NRS produced reliable and valid pain and discomfort rankings for 16 common hospital procedures and experiences . These rankings should prove useful in reducing suffering and can serve as surrogates for quantifying pain and discomfort in dementia patients BACKGROUND Universal pain screening with a 0–10 pain intensity numeric rating scale ( NRS ) has been widely implemented in primary care . OBJECTIVE To evaluate the accuracy of the NRS as a screening test to identify primary care patients with clinical ly important pain . DESIGN Prospect i ve diagnostic accuracy study PARTICIPANTS 275 adult clinic patients were enrolled from September 2005 to March 2006 . MEASUREMENTS We operationalized clinical ly important pain using two alternate definitions : ( 1 ) pain that interferes with functioning ( Brief Pain Inventory interference scale ≥ 5 ) and ( 2 ) pain that motivates a physician visit ( patient-reported reason for the visit ) . RESULTS 22 % of patients reported a pain symptom as the main reason for the visit . The most common pain locations were lower extremity ( 21 % ) and back/neck ( 18 % ) . The area under the receiver operator characteristic curve for the NRS as a test for pain that interferes with functioning was 0.76 , indicating fair accuracy . A pain screening NRS score of 1 was 69 % sensitive ( 95 % CI 60–78 ) for pain that interferes with functioning . Multilevel likelihood ratios for scores of 0 , 1–3 , 4–6 , and 7–10 were 0.39 ( 0.29–0.53 ) , 0.99 ( 0.38–2.60 ) , 2.67 ( 1.56–4.57 ) , and 5.60 ( 3.06–10.26 ) , respectively . Results were similar when NRS scores were evaluated against the alternate definition of clinical ly important pain ( pain that motivates a physician visit ) . CONCLUSIONS The most commonly used measure for pain screening may have only modest accuracy for identifying patients with clinical ly important pain in primary care . Further research is needed to evaluate whether pain screening improves patient outcomes in primary care Abstract The present study investigated whether the level of cognitive impairment ( CI ) affects acute pain behavior and how it is manifested . Participants were 159 individuals ( mean age 42 ± 12 ) , 121 with CI ( divided into four groups according to the level of CI : mild , moderate , severe , profound ) and 38 with normal cognition ( controls ) . The behavior of the participants before and during acute pain ( influenza vaccination ) was coded by two raters with the Facial Action Coding System ( FACS – scores facial reactions to pain ) and the Non‐Communicating Children ’s Pain Checklist ( NCCPC‐R – scores both facial and general body reactions ) . Individuals with severe – profound CI exhibited elevated FACS and NCCPC‐R values at baseline compared with all other groups ( p < 0.01 ) . Both FACS and NCCPC‐R scores of individuals with mild – moderate CI and controls increased significantly during vaccination ( p < 0.001 ) . In contrast , individuals with severe – profound CI exhibited high rates of “ freezing reaction ” ( stillness ) during vaccination , manifested mainly in the face and therefore result ing in elevation of only NCCPC‐R scores but not of FACS ’s . The results suggest that the level of CI affects baseline as well as pain behavior and it is therefore necessary to choose an appropriate behavioral tool to measure pain in these individuals accordingly . For example , tools based on facial reactions alone might provide the false impression that individuals with severe – profound CI are insensitive to pain ( due to freezing ) OBJECTIVES To evaluate the effect of emergency department ( ED ) crowding on assessment and treatment of pain in older adults . DESIGN Retrospective review of ED records from a prospect i ve cohort study . SETTING Urban , academically affiliated , tertiary medical center . PARTICIPANTS One hundred fifty-eight patients , aged 50 and older , evaluated and hospitalized from the ED with hip fracture . MEASUREMENTS Patient-related risk factors : age , sex , nursing home residence , ED triage status , dementia , Acute Physiology in Age and Chronic Health Evaluation II physiological score , and R AND comorbidity score . ED crowding risk factors : ED census and mean length of stay . OUTCOMES documentation of pain assessment , time to pain assessment , time to pain treatment , patients reporting pain receiving analgesia , and meperidine use . RESULTS Mean age was 83 ( range 52 - 101 ) , 81.0 % of patients complained of pain , mean time to pain assessment was 40 minutes ( range 0 - 600 ) , time to treatment was 141 minutes ( range 10 - 525 ) , and mean delay to treatment was 122 minutes ( range 0 - 526 ) . Of those with pain , 35.9 % received no analgesia , 7.0 % received nonopioids , and 57.0 % received opioids . Of those receiving opioids , 32.8 % received meperidine . ED crowding at census levels greater than 120 % bed capacity was significantly associated with a lower likelihood of documentation of pain assessment ( P = .05 ) and longer times to pain assessment ( P = .01 ) . CONCLUSION Older adults with hip fracture are at risk for under assessment of pain , considerable delays in analgesic administration after pain is identified , and treatment with inappropriate analgesics ( e.g. , meperidine ) in the ED . Higher levels of ED census are significantly associated with poorer pain management BACKGROUND Successfully managing pain for the trauma patient decreases morbidity , improves patient satisfaction , and is an essential component of critical care . Using patient-controlled analgesia ( PCA ) morphine to control pain may be complicated by concerns of respiratory depression , hemodynamic instability , addiction , urinary retention , and drug-induced ileus . Morphine is rapidly absorbed by mucosal surfaces in the respiratory tract , achieving systemic concentrations equal to 20 % of equivalent intravenous doses . The purpose of this study was to evaluate the safety , efficacy , and utility of nebulized morphine in patients with posttraumatic thoracic pain . METHODS This double-blinded , prospect i ve study r and omized patients with severe posttraumatic thoracic pain into two groups . The experimental group ( NMS ) received nebulized morphine every 4 hours and normal saline by PCA . The control group ( PCA ) received nebulized saline every 4 hours and morphine by PCA . Dose adjustments were made based on patient response to treatments using a 10-point visual analog scale ( VAS ) for pain . Pulmonary function , pain relief ( VAS ) , level of sedation ( 0 - 3 ) , total drug administration , and systematic side effects were recorded . RESULTS Forty-four patients were r and omized ( 22 per group ) . Seven hundred seventy observations were made . The mean 4-hour dose of morphine was 11.96 + /- 3.4 mg for NMS and 6.22 + /- 4.7 mg for PCA ( p < 0.001 ) . Patients with NMS had lower heart rates compared with PCA ( 79 + /- 11 bpm versus 92 + /- 12 bpm ; p < 0.001 ) and were less se date d ( 0.33 + /- 0.7 versus 0.56 + /- 0.9 ; p = 0.03 ) . The mean pain level ( VAS ) was 3.38 + /- 1.8 for NMS and 3.84 + /- 2.7 for PCA ( p = 0.2 ) . There was no difference between pain levels before and after dosing . There were no differences between groups with respect to arterial blood pressure , respiratory rate , vital capacity , mean forced expiratory volume in 1 second , spirometric volumes , or Sao2 . CONCLUSION Nebulized morphine can be safely and effectively used to control posttraumatic thoracic pain . Pain can be successfully managed while vital capacity , mean forced expiratory volume in one second , and spirometric volumes are maintained . Compared with PCA morphine , nebulized morphine provides equivalent pain relief with less sedative effects OBJECTIVE The objective of this study was to identify the underlying causes of respiratory-related critical events associated with intravenous patient-controlled analgesia ( i.v . PCA ) . DESIGN The design is an observation study of prospect ively collected data . SETTING An Acute Pain Service ( APS ) was established for the management of all patients receiving i.v . PCA therapy for pain management . As part of ongoing care , all respiratory-related critical events were documented and analyzed by staff members of the APS team . PATIENTS All patients receiving i.v . PCA therapy through the APS during the period of May 1990 through October 1992 were enrolled in the study . INTERVENTIONS Evaluation of all respiratory-related critical events was attempted to identify the underlying cause of the event and to determine if measures could be taken to prevent recurrence of similar events . OUTCOME MEASURES Any clinical event that could have or did lead to adverse patient outcome was used as an outcome measure . RESULTS A total of 3,785 patients received PCA therapy for a total of 11,521 patient care days . Fourteen critical events occurred , of which four led to increased patient care . There were eight programming errors ( all involving misprogramming of the continuous infusion ) : three involved a family member activating the device , three were the result of an error in clinical judgment , and one involved a patient tampering with the device ( one event involved more than one error ) . Of the four events that led to increased patient care , two involved a family member activating the device , one was the result of a programming error , and one was the result of an error in clinical judgment . All patients who experienced a critical event had an uneventful recovery . CONCLUSIONS Following review of the critical events , it was determined that the design of the PCA device contributed to the misprogramming errors and the device was removed from service . Changes in the training of physicians and nurses were instituted to avoid recurrence of other errors identified . The incidence of serious respiratory-related critical events was 0.1 % . i.v . PCA therapy has the risk of potentially serious complications and requires constant physician and nursing care with an active quality assurance program OBJECTIVE To compare the efficacies of meperidine and hydromorphone in the treatment for ureteral colic in the emergency department ( ED ) . METHODS A prospect i ve , double-blind , r and omized clinical trial was conducted over six months at a tertiary referral center with 93,000 annual ED visits . Seventy-three patients completed the study . The patients received either 1 mg of hydromorphone or 50 mg of meperidine IV at t = 0 . Pain intensity was determined using a 10-cm visual analog scale at t = 0 , 15 , 30 , 60 , and 120 minutes . A second dose of the study drug could be given between t = 15 and t = 120 minutes when the clinician believed the initial dose was ineffective . Patients requiring more than one additional dose of analgesia were treated as nonresponders and were removed from the study . RESULTS Thirty-six patients received hydromorphone and 37 received meperidine . The initial pain intensities ( hydromorphone group = 8.4 + /- 1.5 ; meperidine group = 8.5 + /- 2.1 ) , age distributions , sex distributions , and side effects of the two groups were comparable . Pain relief was better ( p < 0.05 ) with hydromorphone at t = 15 , 30 , 60 , and 120 minutes . The hydromorphone group required rescue analgesia less often ( 31 % vs 68 % , p < 0.01 ) , had fewer IV pyelographies ( IVPs ) ( 28 % vs 54 % , p < 0.05 ) , and had a lower proportion of hospital admissions ( 25 % vs 49 % , p = 0.08 ) . CONCLUSIONS For the fixed doses used in this study , the adult ureteral colic patients receiving hydromorphone achieved more pain relief , required less rescue medication , underwent fewer IVPs , and avoided hospital admission more frequently than did those receiving meperidine OBJECTIVE To determine whether morphine affects evaluation or outcome for patients with acute abdominal pain . METHODS Prospect i ve , double-blind , placebo-controlled administration of morphine sulfate ( MS ) or normal saline ( NS ) in the setting of acute abdominal pain . The study was performed at a military ED with an annual census of 60,000 visits . Patients > or = 18 years old who had abdominal pain for < or = 48 hours were included . Patients who were allergic to MS or who had systolic blood pressures < 90 mm Hg were excluded . The physicians indicated a provisional diagnosis , a differential diagnosis , and a provisional disposition . Study solution was titrated to the patient 's assessment of adequate analgesia ( up to a volume equivalent of 20 mg of MS ) ; pain response was monitored using a visual analog scale ( VAS ) . The patients were followed until diagnosis occurred or symptoms resolved . RESULTS Of 75 patients enrolled , 71 completed the study ; 35 patients received MS and 36 received NS . More than half ( 44 ; 62 % ) of the patients were admitted from the ED ; 28 patients underwent surgery . The VAS pain level improved more for the MS group , 3.9 + /- 2.8 cm , than it did for the NS group , 0.8 + /- 1.5 cm ( p < 0.01 ) . Study solution dose was less in the MS group than it was in the NS group , 1.5 + /- 0.5 mL vs 1.8 + /- 0.4 mL ( p < 0.01 ) . There was no difference between the groups when comparing accuracy of provisional or differential diagnosis with that of final diagnosis . Differences between provisional and actual dispositions were the same in all groups . There were 3 diagnostic or management errors in each group . CONCLUSIONS When compared with saline placebo , the administration of MS to patients with acute abdominal pain effectively relieved pain and did not alter the ability of physicians to accurately evaluate and treat patients In a double-blind , double-dummy r and omized controlled clinical trial , the onset and duration of the analgesic effect of dipyrone , 1 or 2 g , and diclofenac sodium , 75 mg , by either the i.m . or the i.v . route were compared in 293 patients ( aged 18–70 years ) with acute renal colic . A level of ≥ 50 mm on the 100-mm visual analogue scale was required for inclusion in the study . Patients were r and omly allocated to six treatment groups , receiving dipyrone 1 g i.m . , dipyrone 1 g i.v . , dipyrone 2 g i.m . , dipyrone 2 g i.v . , diclofenac sodium 75 mg i.m . ; and diclofenac sodium 75 mg i.v , respectively . Evaluations were performed at 10 , 20 , 30 , and 60 min and 2 , 4 , and 6 h after treatment ( time 0 ) . Primary efficacy end points included course of pain , total pain , percentage of patients with a pain improvement of 50 % or more at each evaluation time , pain intensity evaluated by the investigator on a 0–3 scale , and differences in pain intensity . The analgesic response was more marked and prolonged among patients receiving dipyrone 2 g i.m . or dipyrone 2 g i.v . There were no significant differences between dipyrone 1 g and diclofenac sodium 75 mg , by either the i.m . or the i.v . route . All treatment regimens were well tolerated Objective : To compare effectiveness , safety , and patient satisfaction of patient controlled analgesia ( PCA ) with titrated , intravenous opioid injections for the management of acute traumatic pain in the emergency department ( ED ) . Methods : The study took place in the ED of a teaching hospital . Patients suffering traumatic injury requiring opioid analgesia , and meeting other inclusion criteria , were consented and r and omised to either the study group or control group . The study group were given morphine through the PCA system , whereas the control group were given morphine via the conventional route of nurse titration . Pain levels were measured using a visual analogue scale . Both groups had their vital signs ( blood pressure , pulse , oxygen saturations , Glasgow coma score , respiratory rate ) and pain scores monitored at 0 , 15 , 30 , 45 , 60 , 90 , and 120 minutes , and any adverse events were noted . Patients were followed up with a question naire asking about their experience of pain relief in the department . Results : 86 patients were recruited to the study , 43 in each group . There was no significant difference between the groups in terms of pain relief ( p = 0.578 ) and patient satisfaction ( p = 0.263 ) . No severe adverse events were observed , although 20.7 % ( n = 9 ) of the PCA group experienced mild sedation compared with 7 % ( n = 3 ) of the control group . Conclusions : PCA is at least as effective as titrated intravenous injections for relief of traumatic pain . It has considerable potential for use in the ED & NA ; The purpose of the study was to compare the psychometric properties of four established pain scales in a population of hospitalized older adults ( mean age , 76 years ) with varying levels of cognitive impairment . Patients made ratings of current pain three times/day for 7 days . They also made retrospective daily , weekly , and bi‐weekly ratings of usual , worst , and least pain levels over a 14‐day period . Ratings were made on four different scales , varying in numeric and verbal dem and s : a five‐point verbal rating scale , a seven‐point faces pain scale , a horizontal 21‐point ( 0–100 ) box scale , and two vertical 21‐point ( 0–20 ) box scales ( measuring pain intensity and pain unpleasantness ) . The accuracy , reliability , construct validity , postdictive validity , and bias susceptibility of each scale were evaluated . The horizontal 21‐point box scale emerged as the best scale with respect to both psychometrics and validity , regardless of mental status . Pain intensity did not vary as a function of mental status . Retrospective estimates of pain varied by mental status : a combination of usual/worst pain was best for cognitively impaired patients , while a combination of usual/least pain was best for unimpaired patients . These findings support the use of the 21‐point box scale for pain assessment in older patients , including those with mild‐to‐moderate cognitive impairment . They also support the ability of older , cognitively impaired patients to rate pain reliably and validly OBJECTIVES To evaluate the quality of pain assessment by emergency medical services ( EMS ) in out-of-hospital emergencies . METHODS A prospect i ve study was conducted on a convenience sample of patients during a one-year observation period . Pain ratings assessed by emergency patients were documented at three different intervals during the emergency call , and compared with concomitant assessment s by EMS providers . A visual analog scale ( VAS ) and a verbal pain scale ( VPS ) were used for pain assessment . Repeated- measures ANOVA and Dunnett 's t-test were used for data analysis . RESULTS Fifty-one out of 70 eligible patients met inclusion criteria . In most emergency patients the intensity of pain was underestimated by EMS , especially when pain was severe ( p = 0.0001 ) . During the course of transport , both pain and pain assessment by EMS improved significantly ( p = 0.0001 ) . The VAS and VPS were significantly correlated ( p = 0.0001 ) . CONCLUSIONS EMS providers significantly underestimate their patients ' pain severity . EMS providers should be more attentive to their patients ' complaints and comfort A r and omised multicentre clinical trial was undertaken to compare the effect on pain of indomethacin administered either intravenously or rectally to 116 patients with ureteric colic . Adverse reactions were also assessed . Of the patients receiving the intravenous injection , 48/53 ( 91 % ) achieved good pain relief ( i.e. no supplementary analgesia was required ) 30 min after administration , compared with 46/63 ( 73 % ) receiving the enema . Significantly more side effects occurred in the group treated intravenously . It was concluded that indomethacin administered as an enema was less effective than the intravenous form , but it should be regarded as a good alternative in the treatment of ureteric colic Abstract BACKGROUND : To improve pain management , the Veterans Health Administration launched the “ Pain as the 5th Vital Sign ” initiative in 1999 , requiring a pain intensity rating ( 0 to 10 ) at all clinical encounters . OBJECTIVE : To measure the initiative ’s impact on the quality of pain management . DESIGN : We retrospectively review ed medical records at a single medical center to compare providers ’ pain management before and after implementing the initiative and performed a subgroup analysis of patients reporting substantial pain ( ≥4 ) during a postimplementation visit . PARTICIPANTS : Unique patient visits selected from all 15 primary care providers of a general medicine outpatient clinic . MEASUREMENTS : We used 7 process indicators of quality pain management , based on appropriately evaluating and treating pain , to assess 300 r and omly selected visits before and 300 visits after implementing the pain initiative . RESULTS : The quality of pain care was unchanged between visits before and after the pain initiative ( P>.05 for all comparisons ) : subjective provider assessment ( 49.3 % before , 48.7 % after ) , pain exam ( 26.3 % , 26.0 % ) , orders to assess pain ( 11.7 % , 8.3 % ) , new analgesic ( 8.7 % , 11.0 % ) , change in existing analgesics ( 6.7 % , 4.3 % ) , other pain treatment ( 11.7 % , 13.7 % ) , or follow-up plans ( 10.0 % , 8.7 % ) . Patients ( n=79 ) who reported substantial pain often did not receive recommended care : 22 % had no attention to pain documented in the medical record , 27 % had no further assessment documented , and 52 % received no new therapy for pain at that visit . CONCLUSIONS : Routinely measuring pain by the 5th vital sign did not increase the quality of pain management . Patients with substantial pain documented by the 5th vital sign often had inadequate pain management OBJECTIVE To evaluate systemic versus epidural opioid administration for analgesia in patients sustaining thoracic trauma . SUMMARY BACKGROUND DATA The authors have previously shown that epidural analgesia significantly reduces the pain associated with significant chest wall injury . Recent studies report that epidural analgesia is associated with a lower catecholamine and cytokine response in patients undergoing elective thoracotomy compared with patient-controlled analgesia ( PCA ) . This study compares the effect of epidural analgesia and PCA on pain relief , pulmonary function , cathechol release , and immune response in patients sustaining significant thoracic trauma . METHODS Patients ( ages 18 to 60 years ) sustaining thoracic injury were prospect ively r and omized to receive epidural analgesia or PCA during an 18-month period . Levels of serum interleukin (IL)-1beta , IL-2 , IL-6 , IL-8 , and tumor necrosis factor-alpha ( TNF-alpha ) were measured every 12 hours for 3 days by enzyme-linked immunosorbent assay . Urinary catecholamine levels were measured every 24 hours . Independent observers assessed pulmonary function using st and ard techniques and analgesia using a verbal rating score . RESULTS Twenty-four patients of the 34 enrolled completed the study . Age , injury severity score , thoracic abbreviated injury score , and length of hospital stay did not differ between the two groups . There was no significant difference in plasma levels of IL-1beta , IL-2 , IL-6 , or TNF-alpha or urinary catecholamines between the two groups at any time point . Epidural analgesia was associated with significantly reduced plasma levels of IL-8 at days 2 and 3 , verbal rating score of pain on days 1 and 3 , and maximal inspiratory force and tidal volume on day 3 versus PCA . CONCLUSIONS Epidural analgesia significantly reduced pain with chest wall excursion compared with PCA . The route of analgesia did not affect the catecholamine response . However , serum levels of IL-8 , a proinflammatory chemoattractant that has been implicated in acute lung injury , were significantly reduced in patients receiving epidural analgesia on days 2 and 3 . This may have important clinical implication s because lower levels of IL-8 may reduce infectious or inflammatory complications in the trauma patient . Also , tidal volume and maximal inspiratory force were improved with epidural analgesia by day 3 . These results demonstrate that epidural analgesia is superior to PCA in providing analgesia , improving pulmonary function , and modifying the immune response in patients with severe chest injury PURPOSE S This study was design ed to evaluate the ability of a triage pain protocol to improve frequency and time to delivery of analgesia for musculoskeletal injuries in the emergency department ( ED ) . BASIC PROCEDURES Frequency and time to analgesic administration were measured before and after use of a triage pain protocol . The protocol allowed analgesic medications to be given at the time of triage . MAIN FINDINGS Time to medication administration was 76 minutes ( 95 % confidence interval [ CI ] , 68 - 84 minutes ) before and 40 minutes ( 95 % CI , 32 - 47 minutes ) after the protocol . Five hundred fifty-nine ( 70 % ) of 800 patients received analgesics using the protocol compared with 212 of 471 ( 45 % ) patients prior . PRINCIPAL CONCLUSIONS Use of a triage pain protocol increased the number of patients with musculoskeletal injury who received pain medication in the ED . Use of the protocol also result ed in a decrease in the time to analgesic medication administration The objective of this study was to determine if judicious dosing of morphine sulfate can provide pain relief without changing important physical examination findings in patients with acute appendicitis . We conducted a prospect i ve , r and omized , double-blind crossover design . Patients scheduled for appendectomy were r and omized to two groups . Group A received 0.075 mg/kg intravenous morphine sulfate and 30 minutes later received placebo . The sequence of medication was reversed in group B. Patients were examined by a surgical resident and an EM attending before and after receiving medication . Six explicit physical examination findings were documented as absent , indeterminate , or present . Physicians were also asked if they felt overall examination findings had changed after medication . Patient 's visual analog scale ( VAS ) was recorded before each medication and at study completion . Thirty-four patients were enrolled and full data were available for 22 patients . Neither morphine nor placebo caused a significant change in individual examination findings . Three patients in both groups were judged to have a change in their examination after medication . The median change in VAS was 20 mm after morphine and 0 mm after placebo ( P = .01 ) . In this pilot study , patients with clinical signs of appendicitis were treated with morphine and had significant improvement of their pain without changes in their physical examination Rectal administration of 100 mg indomethacin in solution had as good , and almost as rapid , an effect on renal colic as 50 mg given intravenously . Side effects were significantly fewer with the rectal than with the intravenous route A prospect i ve study of Emergency Medicine ( EM ) residents was conducted over two consecutive 1-month periods at a rural tertiary-care teaching hospital with a residency in EM to evaluate the effect of a 4-h pain management education program on the assessment and management of acute pain in the emergency department ( ED ) . All patients presenting to the ED with an acute , painful condition were eligible to participate in the survey . Patients were excluded if they had taken any pain medication within 4 h of presenting to the ED , or had any condition requiring immediate resuscitation , suspected cardiac pain , or pain from a potential surgical abdomen . Baseline and 30-min pain scores were evaluated using a 100-mm , unnumbered visual analog scale ( VAS ) . A 4-h pain management educational program ( EP ) aim ed toward the EM residents was conducted . Comparisons were made with respect to the overall treatment of pain as evaluated by the change in VAS score between baseline and 30 min as well as the global assessment of treatment . A total of 126 surveys were completed , 54 before ( Group 1 ) and 72 after ( Group 2 ) the EP . The mean deltaVAS score for patients in Group 2 was significantly better than the deltaVAS score for patients in Group 1 . Only 65 % of the patients studied before the EP had significant reduction in their pain scores after 30 min in the ED ; after institution of the EP , 92 % had a significant reduction in their pain scores at 30 min . Similarly , a significant improvement was seen in the patients ' global evaluation of treatment after the educational program was instituted . It appears that the use of a 4-h educational program on pain assessment and management directed toward EM residents in their training can improve their skills at recognizing and treating painful conditions OBJECTIVES To assess the performance of self- assessment scales in severely demented hospitalized patients and to compare it with observational data . DESIGN Prospect i ve clinical study . SETTING Geriatrics hospital and a geriatric psychiatry service . PARTICIPANTS All patients who met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for dementia , with a Mini-Mental State Examination score less than 11 and a Clinical Dementia Rating score of 3 . MEASUREMENTS Three self- assessment tools -- the verbal , horizontal visual , and faces pain scales -- were administered in r and omized order . A nursing team independently completed an observational pain rating scale . Main outcomes were comprehension ( ability to explain scale use and correctly indicate positions for no pain and extreme pain , on two separate occasions ) , inter- and intrarater reliability , and comparison of pain intensities measured by the different scales . RESULTS Sixty-one percent of 129 severely demented patients ( mean age 83.7 , 69 % women ) demonstrated comprehension of at least one scale . Comprehension rates were significantly better for the verbal and the faces pain scales . For patients who demonstrated good comprehension , the inter- and intrarater reliability of the three self- assessment scales was high ( intraclass correlation coefficient=0.88 - 0.98 ) . Correlation between the three self- assessment scales was moderate to strong ( Spearman correlation coefficient (r)=0.45 - 0.94 ; P<.001 ) . Observational rating correlated at least moderately with self- assessment ( r=0.25 - 0.63 ) , although for patients reporting pain , the observational rating scale underestimated severity compared with all three self- assessment scales . CONCLUSION Clinicians should not apply observational scales routinely in severely demented patients , because many are capable of reliably reporting their own pain Background . It is generally agreed that r and omized controlled trials should be powered to detect small but clinical ly significant treatment effects . Toward these ends , minimal important difference ( MID ) was proposed as a benchmark for design ing trials and for interpreting health-related quality -of-life instrument scores . MID was defined in 1989 as “ the smallest difference in score in the domain of interest which patients perceive as beneficial and which would m and ate , in the absence of troubling side effects and excessive cost , a change in the patient ’s management . ” Objective . 1 ) To exp and the idea of minimal clinical ly important difference so as to take into account harms as well as benefits . 2 ) To propose concepts and methods with which to do so . Summary . The authors define sufficiently important difference ( SID ) as the smallest amount of patient-valued benefit that an intervention would require to justify associated costs , risks , and other harms . As a means toward estimation of SID , the authors propose benefit-harm tradeoff methods , in which domains of benefit and harm are systematic ally traded off against each other and assessed in relation to the global decision of whether a treatment choice is worthwhile . Specific SID estimates can be used to power and interpret clinical trials or to inform health services research and /or public health policy . This article briefly describes the evolution of the important difference concept and outlines similarities and differences between MID and SID Background : Recent trials suggest that the early administration of analgesia in patients with acute abdominal pain facilitates examination and does not delay diagnosis . We investigated current practice regarding analgesia for these patients . Methods : All patients admitted via the accident and emergency department with abdominal pain were included . The main outcome measures evaluated were waiting time for analgesia and its relationship to subjective visual analogue pain scores and clinical diagnoses . Results : Data from 107 consecutive patients were investigated ; seven patients were excluded . Forty-two per cent were male . The mean age was 40.1 years ( 6–85 ) . The mean overall waiting time for analgesia was 1.4 h ( 2 min to 14 h ) . Sixty-seven per cent received analgesia within one hour , although 22 % waited 2–14 h after presentation . Those with mild pain waited significantly longer for analgesia ( mean 247 min ) than those with severe pain ( mean 82 min ; P=0.01 ) . Those with moderate pain had intermediate waiting times ( mean 111 min ) , although they were not statistically different from the severe group ( P=0.43 ) . Female patients had to wait longer ( mean 129 min ) than male patients ( mean 69 min ; P=0.09 analysis of variance ) . Of 64 % who were general practitioner referrals , only 11 % ( all severe group , P=0.02 ) received analgesia in the community . Neither clinical diagnosis nor age influenced the timing of analgesia . Seventy-three per cent received analgesia in the casualty department ( mean 0.5 h ; range 0.02–3.2 ) , whereas those admitted in the ward without receiving analgesia in casualty had to wait significantly longer for their pain relief ( mean 5 h ; 1.2–14 ) . Conclusion : This study shows the need for st and ardized protocol s for analgesia usage in patients presenting with acute abdominal pain |
2,197 | 32,248,987 | Longitudinal effects can influence the expression of decision regret , yet many studies are not design ed to collect long-term data ; prostate cancer studies may be particularly disadvantaged . | OBJECTIVES To perform a systematic review of decision regret studies in cancer patients to determine if regret is longitudinally stable , and whether these study structures account for late-emerging treatment effects . | Purpose To determine if particular values clarification exercises included in a patient decision aid had discernible impact on postdecisional regret in patients with early-stage prostate cancer . Methods A multicenter r and omized controlled trial compared 2 versions of a computerized patient decision aid : only structured information compared to the structured information plus values clarification exercises . Assessment s were conducted during the decision aid visit ; telephone follow-up interviews were conducted when patients made their decisions with their physician , 3 months after completing treatment , and > 1 year later ( per a mailing ) . Outcome measures included the Decisional Conflict Scale , the Preparation for Decision Making Scale , and the Decision Regret Scale . Results A total of 156 patients participated , 75 provided information only and 81 provided information plus values clarification exercises . The groups did not differ significantly on any outcome evaluated at the decision aid visit ; in both groups , decisional conflict decreased immediately after using the decision aid . Between-group differences emerged after the decision was actually made . The values clarification exercises group reported higher Preparation for Decision Making Scale scores at the decision follow-up and at the > 1-year follow-up . Regret did not differ significantly between groups at the 3-month follow-up but was lower for the values clarification exercises group than for the information group at the > 1-year follow-up . Conclusion The results suggest that the values clarification exercises led to better preparation for decision making and to less regret . The impact , however , only emerged after the decision was made Background : Fertility is a priority for many young women with breast cancer . Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions . This study aim ed to prospect ively evaluate the efficacy of a fertility-related decision aid ( DA ) . Methods : A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics , aged 18–40 years and desired future fertility , were assessed on decisional conflict , knowledge , decision regret , and satisfaction about fertility-related treatment decisions . These were measured at baseline , 1 and 12 months , and were examined using linear mixed effects models . Results : Compared with usual care , women who received the DA had reduced decisional conflict ( β=−1.51 ; 95%CI : −2.54 to 0.48 ; P=0.004 ) and improved knowledge ( β=0.09 ; 95%CI : 0.01–0.16 ; P=0.02 ) , after adjusting for education , desire for children and baseline uncertainty . The DA was associated with reduced decisional regret at 1 year ( β=−3.73 ; 95%CI : −7.12 to −0.35 ; P=0.031 ) , after adjusting for education . Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility ( P<0.001 ) , fertility options ( P=0.005 ) , and rated it more helpful ( P=0.002 ) , than those who received st and ard care . Conclusion : These findings support widespread use of this DA shortly after diagnosis ( before chemotherapy ) among younger breast cancer patients who have not completed their families Background : To examine the impact of race on treatment regret among men with recurrent prostate cancer after surgery or radiation . Methods : The prospect i ve Comprehensive , Observational , Multicenter , Prostate Adenocarcinoma ( COMPARE ) registry was used to study a cohort of 484 men with biochemically recurrent prostate cancer after radical prostatectomy , external beam radiation or brachytherapy . Multivariable logistic regression was used to model the association between race and treatment regret and to determine whether there was an interaction between race and sexual problems after treatment with regards to treatment regret . Results : Black men ( N=78 ) were significantly more likely to have treatment regret when compared with non-black men ( N=406 ; 21.8 % versus 12.6 % ) on univariable analysis ( odds ratio ( OR ) 1.94 ; 95 % confidence interval 1.05–3.56 ; P=0.03 ) . On multivariable analysis , black race trended towards but was no longer significantly associated with an increase in treatment regret ( adjusted OR ( AOR ) 1.84 ( 0.95–3.58 ) ; P=0.071 ) . There was an interaction between race and sexual problems after treatment ( Pinteraction=0.02 ) such that among those without sexual problems , black men had more treatment regret than non-black men ( 26.7 % versus 8.4 % : AOR 4.68 ( 1.73–12.63 ) ; P=0.002 ) , whereas among those with sexual problems , there was no difference in treatment regret between black and non-black men ( 18.8 % versus 17.3 % : AOR 1.04 ( 0.44–2.46 ) ; P=0.93 ) . Conclusions : Among men with recurrent prostate cancer after surgery or radiation , black men were nearly twice as likely to experience treatment regret . Treating physicians should ensure that patients are fully apprised of the pros and cons of all treatment options to reduce the risk of subsequent regret PURPOSE Breast cancer ( BC ) decision aid ( DA ) r and omized studies are limited to DA use in consultations among Western population s and for primary surgery . Their effectiveness beyond consultations , for reconstructive surgery and in other population s , has not been evaluated . We developed a DA administered after consultation for Chinese women deciding on BC surgery and , where relevant , immediate breast reconstruction , which was evaluated in this r and omized controlled trial ( RCT ) . PATIENTS AND METHODS Overall , 276 women considering BC surgery for early-stage BC were r and omly assigned to receive a DA ( take-home booklet ) or the st and ard information booklet ( control condition ) after the initial consultation , wherein surgeons disclosed the diagnosis and discussed treatment options with patients . Using block r and om assignment by week , 138 women were assigned to the DA arm and 138 to the control arm . Participants completed interview-based question naires 1 week after consultation and then 1 , 4 , and 10 months after surgery . Primary outcome measures were decisional conflict , decision-making difficulties , BC knowledge 1 week after consultation , and decision regret 1 month after surgery . Secondary outcome measures were treatment decision , decision regret 4 and 10 months after surgery , and postsurgical anxiety and depression . RESULTS The DA group reported significantly lower decisional conflict scores 1 week after consultation ( P = .016 ) compared with women in the control arm . Women receiving the DA had significantly lower decision regret scores 4 ( P = .026 ) and 10 months ( P = .014 ) after surgery and lower depression scores 10 months after surgery ( P = .001 ) . CONCLUSION This RCT demonstrated DAs may benefit Chinese patients in Hong Kong by reducing decisional conflict and subsequent regret and enhance clinical services for this population PURPOSE Underst and ing the distinctive patterns of treatment-related dysfunction after alternative initial treatments for early prostate cancer ( PC ) may improve patients ' choice of treatment and later help them adjust to its consequences . We characterized the time course of treatment complications while adjusting for potentially confounding pretreatment factors hindering other observational studies . PATIENTS AND METHODS In a prospect i ve cohort study of 417 men we assessed urinary , bowel , and sexual function from before primary treatment to 24 months after . To control for potential confounding , we measured sociodemographic and PC prognostic factors , medical comorbidity , and pretreatment function commonly affected by PC and its treatment . RESULTS Patients who underwent external beam radiotherapy ( EBRT ) , radical prostatectomy ( RP ) , and brachytherapy ( BT ) differed significantly in sociodemographic factors , cancer prognostic factors , and pretreatment symptom status , especially sexual function . Urinary incontinence increased sharply after RP , while bowel problems and urinary irritation/obstruction rose after EBRT and BT . Sexual dysfunction increased in all patients , particularly after radical prostatectomy , and nerve-sparing surgical technique had little apparent benefit . There was no change in urinary function and little change in overall bowel function after 12 months , but the time course of sexual dysfunction varied by treatment and , for bowel function , by symptom . Multiple regression modeling confirmed that treatment influences all 24-month outcomes , but residual confounding persisted . CONCLUSION Pretreatment function and the primary treatment modality for early stage PC strongly predict the affected organ systems and time course of dysfunction . With this information , patients and their physicians may refine their choice of treatment and better anticipate its consequences OBJECTIVE To describe relationships between use of the Personal Patient Profile-Prostate ( P3P ) decision support system and patient characteristics , and perceived preparation for decision making ( PrepDM ) , satisfaction and decisional regret in the context of prostate cancer treatment choice . METHODS 494 men with localized prostate cancer ( LPC ) were r and omized to receive the P3P intervention or usual care and completed pre-treatment , 1-month and 6-month outcome measures . Multivariable linear regression models were fit for each outcome . RESULTS Physician consult visits prior to enrollment , race/ethnicity , and use of clinic-provided books were significant predictors of perceived PrepDM at 1 month . Prior Internet use and PrepDM significantly predicted 6-month decision satisfaction . Decisional regret was significantly predicted by demographics , anxiety , PrepDM score , and EPIC bowel domain score at 6 months . Use of P3P did not predict any outcome . CONCLUSION While the P3P intervention did not significantly affect the outcomes , pre-enrollment information and preparation were strong predictors of the 1- and 6-month outcomes . Decision regret was significantly influenced by personal characteristics and post-treatment symptoms/side effects . PRACTICE IMPLICATION S Information received and used between biopsy and the treatment options consult visit is likely to make a difference in decision satisfaction OBJECTIVE To investigate the effect of including an online decision aid ( DA ) during prostate cancer treatment counseling on decisional regret and information satisfaction in a one-year follow-up . METHODS Within a cluster RCT , 18 Dutch hospitals were r and omized to DA counseling or care-as-usual , patients ( n = 382 ) initially completed question naires directly after treatment decision making . Six and twelve months later regret ( Decisional Regret Scale ) and information satisfaction ( SCIP-B ) were assessed . Anxious and depressive symptoms ( HADS ) was included as possible covariate . RESULTS After 12 months , 43 participants ( 15 % ) regretted their treatment choice and 105 participants ( 36 % ) were dissatisfied with the information that was received at the time of decision-making , regardless of being exposed to the DA . Anxious and depressive symptoms at follow-up were associated with regret and information dissatisfaction . CONCLUSION No long-term benefical effects emerged from DA usage compared to patients who underwent st and ard counseling . PRACTICE IMPLICATION S During PCa treatment counseling , healthcare providers should be aware of anxious and depressive symptoms Effect sizes are the currency of psychological research . They quantify the results of a study to answer the research question and are used to calculate statistical power . The interpretation of effect sizes — when is an effect small , medium , or large ?— has been guided by the recommendations Jacob Cohen gave in his pioneering writings starting in 1962 : Either compare an effect with the effects found in past research or use certain conventional benchmarks . The present analysis shows that neither of these recommendations is currently applicable . From past publications without pre- registration , 900 effects were r and omly drawn and compared with 93 effects from publications with pre- registration , revealing a large difference : Effects from the former ( median r = 0.36 ) were much larger than effects from the latter ( median r = 0.16 ) . That is , certain biases , such as publication bias or question able research practice s , have caused a dramatic inflation in published effects , making it difficult to compare an actual effect with the real population effects ( as these are unknown ) . In addition , there were very large differences in the mean effects between psychological sub-disciplines and between different study design s , making it impossible to apply any global benchmarks . Many more pre-registered studies are needed in the future to derive a reliable picture of real population effects In this prospect i ve , longitudinal study the authors examined changes in cognitive , emotional , and interpersonal components of prostate cancer-related quality of life in 71 men who underwent robotic-assisted prostatectomy for prostate cancer . They identified significant changes across several quality -of-life domains from presurgery to 3-months and 1-year postsurgery . Although some components of quality of life returned to baseline by one year postsurgery , decrements in sexual intimacy , sexual confidence , and masculine self-esteem were enduring . These data can be used to guide patients in their expectations for quality of life following robotic prostatectomy and highlight the need for multidisciplinary approaches aim ed at improving men 's sexual adjustment after this procedure PURPOSE Hypospadias repair is a commonly performed procedure . Little is known about decisional regret in parents who agree to proceed with this surgical reconstruction . We present data on this previously underexplored issue . MATERIAL S AND METHODS We performed followup analysis of 100 couples prospect ively evaluated after counseling for surgical correction of distal hypospadias in their son with assessment of complications and decisional regret 1 year after surgery . Findings were contrasted with baseline demographics , hypospadias knowledge and decisional conflict at the time of counseling . RESULTS Decisional regret was found in 116 parents , including mild regret in 41.4 % and moderate to severe regret in 8.6 % . There was no statistically significant difference in paired regret analysis between mothers and fathers . Complications were strongly associated with decisional regret ( p < 0.001 ) . On regression analysis postoperative complications ( OR 14.7 , 95 % CI 1.6 - 131.6 ) , parental desire to avoid circumcision ( OR 7.4 , 95 % CI 1.1 - 49.4 ) and initial decisional conflict level ( OR 1.06 , 95 % CI 1.02 - 1.09 ) were statistically significant predictors of moderate to strong decisional regret . These findings remained robust after imputation strategies to address missing data . The impact of decisional conflict and preference for circumcision were significant even after excluding families who experienced complications . CONCLUSIONS To our knowledge this is the first study demonstrating parental decisional regret after providing consent for surgical correction of distal hypospadias in their son . Based on the described risk factors efforts aim ed at minimizing complications and counseling about foreskin preservation techniques may be prudent to ameliorate decisional regret . The novel association between decisional conflict and regret suggests that conflict assessment during counseling may help screen families at risk for postoperative regret |
2,198 | 24,008,171 | Both TOF-MRA and contrast-enhanced MRA are shown to be highly accurate for detection of any recanalization in intracranial aneurysms treated with endovascular coil occlusion | MR angiography is proposed as a safer and less expensive alternative to the reference st and ard , DSA , in the follow-up of intracranial aneurysms treated with endovascular coil occlusion .
We performed a systematic review and meta- analysis to evaluate the accuracy of TOF-MRA and contrast-enhanced MRA in detecting residual flow in the follow-up of coiled intracranial aneurysms . | Introduction Since digital subtraction angiography ( DSA ) carries a low risk of morbidity , and is associated with patient discomfort and higher cost , our objective was to determine whether high-resolution 3-D time-of-flight MR angiography ( TOF-MRA ) at 3 T may replace DSA in the follow-up of patients after coiling of an intracranial aneurysm . Methods This prospect i ve study included 50 consecutive patients with a ruptured and subsequently coiled intracranial aneurysm . All patients were followed up at a mean of 14 months after coiling with DSA and high-resolution 3-D TOF-MRA at 3 T generating 0.02 mm3 isotropic voxels . One examiner used DSA and TOF-MR angiograms to assess the need for and risk of retreatment ; these data were used to calculate intermodality agreement . Another two examiners independently assessed aneurysm occlusion by DSA and TOF-MRA according to the Raymond scale ; these data were used to calculate interobserver agreement . Results Discrepancies between DSA and TOF-MRA were found in three patients ( intermodality agreement κ = 0.86 ) . While DSA indicated complete aneurysm occlusion , TOF-MRA showed small neck remnants in the three patients . Coils on all DSA projections obscured these three neck remnants . Interobserver agreement was higher for DSA ( κ = 0.82 ) than for TOF-MRA ( κ = 0.68 ) , which was in part due to the complexity of the information provided by TOF source images and reconstructions . Conclusion 3-D TOF-MRA at 3 T is not only an adjunctive tool but is ready to replace DSA in the follow-up of patients with previously coiled intracranial aneurysms . Additional DSA may only be performed in complex and not clearly laid out aneurysms BACKGROUND AND PURPOSE Digital subtraction angiography ( DSA ) is used to follow-up intracranial aneurysms treated with detachable coils to identify recurrence and determine need for additional treatment . However , DSA is invasive and involves a small risk of neurologic complications . We assessed the feasibility and usefulness of 3D time-of-flight ( TOF ) MR angiography ( MRA ) performed at 3 T compared with DSA for the follow-up of coil-treated intracranial aneurysms . METHODS In a prospect i ve study , 20 consecutive patients with 21 intracranial aneurysms treated with coils underwent DSA and nonenhanced and enhanced multiple overlapping thin-slab acquisition 3D TOF MRA at 3 T on the same day at a mean follow-up of 6 months ( range , 4 - 14 months ) after coil placement . MRA images were evaluated for presence of artifacts , presence and size of aneurysm remnants and recurrences , patency of parent and branch vessels , and added value of contrast material enhancement . MRA and DSA findings were compared . RESULTS Interobserver agreement of MRA was good , as was agreement between MRA and DSA . All three recurrences that needed additional treatment were detected with MRA . Minor disagreement occurred in four cases : three coil-treated aneurysms were scored on MRA images as having a small remnant , whereas on DSA images these aneurysms were occluded ; the other aneurysm was scored on MRA images as having a small remnant , whereas on DSA images this was a small recurrence . Use of contrast material had no additional value . Coil-related MR imaging artifacts were minimal and did not interfere with evaluation of the occlusion status of the aneurysm . CONCLUSION High-spatial-resolution 3D TOF MRA at 3 T is feasible and useful in the follow-up of patients with intracranial aneurysms treated with coil placement Background and Purpose — The purpose of this study was to estimate the performance measures of MR angiography ( MRA ) in the diagnosis of aneurysm residual flow after coil occlusion . Methods — Patients having at least 1 cerebral aneurysm treated with coil occlusion were prospect ively and consecutively enrolled . Time of flight and contrast-enhanced MRA were performed the same day of the DSA follow-up . The degree of aneurysm occlusion and dimensions of the residual flow were evaluated by independent readers at MRA and digital subtraction angiogram . MRA performance measures were estimated in a cross-sectional analysis and repeated in subgroups of aneurysm sizes and locations . MRA predictive values for recurrence were also estimated using a longitudinal design . Results — We obtained 167 aneurysm evaluations for each imaging modality . Class 3 residual flow was seen on digital subtraction angiogram follow-up in 27 % . The sensitivity and specificity of MRA was 88 % ( 95 % CI , 80–94 ) and 79 % ( 95 % CI , 67–88 ) , respectively . The positive predictive value for a Class 3 recurrence was 67 % ( 95 % CI , 51–80 ) and the negative predictive value was 93 % ( 95 % CI , 86–97 ) . Time-of-flight MRA underestimated the length of the residual flow ( P=0.039 ) , whereas contrast-enhanced MRA overestimated its width ( P<0.0001 ) . MRA sensitivity for a Class 3 residual flow was lower for aneurysms < 6 mm ( P=0.01 ) . Conclusions — MRA has sufficient accuracy for screening of aneurysm residual flow after coil occlusion . Due to its lower negative predictive value , recurrent aneurysms should be confirmed with digital subtraction angiogram before planning a retreatment . Routine use of MRA to follow small aneurysms should wait better estimation of its performance in this particular subgroup Background and Purpose — We sought to better define the morbidity of endovascular Guglielmi detachable coil ( GDC ) treatment of unruptured cerebral aneurysms and to discuss its role in the prevention of subarachnoid hemorrhage . Methods — We conducted an observational study from August 1992 to June 1999 of 125 unruptured aneurysms treated with GDC in 116 patients : 91 women ( 78.4 % ) and 25 men ( 21.6 % ) , aged 30 to 78 years ( mean age , 50.6 years ) . Immediate and late clinical results were recorded for any neurological event or hemorrhage related to the treated unruptured aneurysm . Angiographic results are reported as immediate , early ( 2 to 12 months ) , intermediate ( 12 to 30 months ) , and late follow-up ( > 30 months ) . Results — Immediate angiographic results showed complete obliteration ( class 1 ) in 59 ( 47.2 % ) or residual neck ( class 2 ) in 53 aneurysms ( 42.4 % ) , leaving 6 residual aneurysms ( 4.8 % ) and 7 failures ( 5.6 % ) . Early follow-up angiograms , available in 100 treated aneurysms ( 84 % ) , revealed class 1 in 52 % and class 2 in 41 % . Intermediate angiograms , available in 53 aneurysms ( 44.5 % ) , showed class 1 in 47.2 % and class 2 in 43.4 % , while late results , available in 37 lesions ( 31.1 % ) , had class 1 and 2 in 48.6 % and 37.8 % , respectively . Six patients suffered a permanent neurological deficit at last follow-up ( 5.2 % ) , with a good outcome in 5 patients and fair outcome in 1 patient . There was no mortality . There was no aneurysmal rupture during a mean clinical follow-up of 32.1 months . Conclusions — Endovascular treatment with GDC for unruptured aneurysms is relatively safe . Its role in the prevention of aneurysmal rupture remains to be determined , preferably by a r and omized study BACKGROUND AND PURPOSE : Blood-pool agents are promising in the imaging of small vessels with slow or complex flow . Our aim was to compare blood-pool contrast-enhanced MR angiography ( BPCE-MRA ) using gadofosveset trisodium ( Vasovist ) with 3D time-of-flight MRA ( TOF-MRA ) in the follow-up of intracranial aneurysms after endovascular therapy . MATERIAL S AND METHODS : We included 32 patients with a total of 37 coiled aneurysms . MRAs in the early steady-state phase were performed on a 1.5 T scanner within 8 days of digital subtraction angiography ( DSA ) . Two radiologists independently analyzed TOF-MRA and BPCE-MRA images . Consensus was reached by review involving a third neuroradiologist . DSA images were interpreted separately by an interventional radiologist . Findings were assigned to 1 of 3 categories : 1 ) complete occlusion , 2 ) residual neck , and 3 ) residual aneurysm . RESULTS : Follow-up DSA demonstrated 13 complete obliterations ( class 1 ) , 13 residual necks ( class 2 ) , and 11 residual aneurysms ( class 3 ) . Weighted κ statistics showed substantial concordance of TOF-MRA and DSA ( 0.664 ) as well as BPCE-MRA and DSA ( 0.724 ) ratings . Comparison between TOF-MRA and BPCE-MRA found excellent agreement ( 0.818 ) with only 6 ( 16.2 % ) discrepancies . For detecting residual flow , the difference in accuracy of both MRA techniques ( 83.8 % versus 91.9 % ) was not significant ( McNemar , P = 1.000 ) . BPCE-MRA showed a tendency towards higher sensitivity and specificity ( 91.7 % and 92.3 % , respectively ) compared with TOF-MRA ( 87.5 % and 76.9 % ) . CONCLUSIONS : In classifying the completeness of endovascular cerebral aneurysm therapy , we found that BPCE-MRA and 3D TOF-MRA showed very good agreement . The use of Vasovist did not lead to a significantly increased accuracy of MRA follow-up BACKGROUND AND PURPOSE : MR angiography ( MRA ) is increasingly used as a noninvasive imaging technique for the follow-up of coiled intracranial aneurysms . However , the need for contrast enhancement has not yet been eluci date d. We compared 3D time-of-flight MRA ( TOF-MRA ) and contrast-enhanced MRA ( CE-MRA ) at 3 T with catheter angiography . MATERIAL S AND METHODS : Sixty-seven patients with 72 aneurysms underwent TOF-MRA , CE-MRA , and catheter-angiography 6 months after coiling . Occlusion status on MRA was classified as adequate ( complete and neck remnant ) or incomplete by 2 independent observers . For TOF-MRA and CE-MRA , interobserver agreement , intermodality agreement , and correlation with angiography were assessed by κ statistics . RESULTS : Catheter-angiography revealed incomplete occlusion in 12 ( 17 % ) of the 69 aneurysms ; 3 aneurysms were excluded due to MR imaging artifacts . Interobserver agreement was good for CE-MRA ( κ = 0.77 ; 95 % confidence interval [ CI ] , 0.55–0.98 ) and very good for TOF-MRA ( κ = 0.89 ; 95 % CI , 0.75–1.00 ) . Correlation of TOF-MRA and CE-MRA with angiography was good . The sensitivity of TOF-MRA and CE-MRA was 75 % ( 95 % CI , 43%–95 % ) ; the specificity of TOF-MRA was 98 % ( 95 % CI , 91%–100 % ) and of CE-MRA , 97 % ( 95 % CI , 88%–100 % ) . All 5 incompletely occluded aneurysms , which were additionally treated , were correctly identified with both MRA techniques . Areas under the receiver operating characteristic curve for TOF-MRA and CE-MRA were 0.90 ( 95 % CI , 0.79–1.00 ) and 0.91 ( 95 % CI , 0.79–1.00 ) . Intermodality agreement between TOF-MRA and CE-MRA was very good ( κ = 0.83 ; 95 % CI , 0.65–1.00 ) , with full agreement in 66 ( 96 % ) of the 69 aneurysms . CONCLUSIONS : In this study , TOF-MRA and CE-MRA at 3 T were equivalent in evaluating the occlusion status of intracranial aneurysms after coiling . Because TOF-MRA does not involve contrast administration , this method is preferred over CE-MRA In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias The purpose of this study was to evaluate time-of-flight magnetic resonance angiography ( MRA ) in the follow-up of intracranial aneurysms treated with Guglielmi detachable coils ( GDCs ) . From January 1998 to January 2002 27 MRA and intra-arterial digital subtraction angiography ( IADSA ) examinations were analyzed for residual aneurysms and arterial patency following GDC placement . A total number of 33 intracranial aneurysms was analyzed , including 18 located in the posterior circulation . The MRA analysis was based on source images in combination with maximum intensity projections . The IADSA was used as the reference st and ard . Two aneurysms were excluded from evaluation , because of susceptibility artefacts from other aneurysms , which were clipped . Sensitivity and positive predictive values of MRA in revealing residual aneurysms were , respectively , 89 % and 80 % . Specificity in ruling out remnant necks and residual flow around coils was , respectively , 91 % and 97 % , with a negative predictive value of , respectively , 95 % and 100 % . Specificity and negative predictive value of MRA for arterial occlusion were , respectively , 87 % and 100 % for the parent arteries and , respectively , 85 % and 100 % for the adjacent arteries . MRA is a reliable diagnostic tool in the follow-up of GDC treatment , and it may replace IADSA in excluding residual flow around coils and aneurysmal necks and in ruling out arterial occlusion BACKGROUND AND PURPOSE : A substantial percentage of coiled aneurysms are associated with persistent filling of an aneurysmal component due to incomplete initial treatment or re-growth . Traditionally follow-up of coiled aneurysms has consisted of repeated intra-arterial cerebral catheter angiography , an invasive procedure with associated risks . Hence , many authors have advocated the use of non-invasive imaging techniques for this purpose . Our aim was to compare contrast-enhanced MR angiography ( CE-MRA ) with digital subtraction angiography ( DSA ) for depiction of aneurysmal remnants of coiled cerebral aneurysms . MATERIAL S AND METHODS : Aneurysms coiled between September 2003 and October 2006 were retrospectively review ed . We included patients meeting the following criteria : 1 ) residual/recurrent aneurysm measuring 2 mm or greater , and 2 ) CE-MRA and DSA performed no more than 60 days apart . Three readers were asked to determine which technique was superior for characterization of the aneurysmal remnant : CE-MRA , DSA , or indeterminate . Statistical analysis included most rule and κ statistics . RESULTS : Of 232 patients who underwent coiling , 44 met the inclusion criteria ( 33 women and 11 men ; 24–72 years of age ) . Sixteen patients had neck remnants and 28 had body remnants . The first study to identify the remnant was DSA in 35 patients and CE-MRA in 9 . In 32 patients ( 32/44 , 73 % ) , the readers indicated that CE-MRA was superior to DSA for remnant characterization . CE-MRA and DSA were thought to be equivalent in 7 ( 16 % ) , and DSA was preferred in 3 ( 7 % ) . Two cases ( 5 % ) yielded ambiguous results . Of the 28 body remnants , 22 ( 78.6 % ) were characterized by remnant protrusion into the coil mass : In 20 of these ( 91 % ) , the readers preferred CE-MRA over DSA , and in 2 cases ( 9 % ) , the techniques were thought to be equivalent . CONCLUSION : In patients with known aneurysm remnants , CE-MRA is at least equivalent to DSA for characterization of aneurysmal remnants after coiling . Contrast filling within the coil mass was more clearly seen with CE-MRA than with DSA In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Background and Purpose — Our aim in this study was to assess the incidence and determining factors of angiographic recurrences after endovascular treatment of aneurysms . Methods — A retrospective analysis of all patients with selective endosaccular coil occlusion of intracranial aneurysms prospect ively collected from 1992 to 2002 was performed . There were 501 aneurysms in 466 patients ( mean±SD age , 54.20±12.54 years ; 74 % female ) . Aneurysms were acutely ruptured ( 54.1 % ) or unruptured ( 45.9 % ) . Mean±SD aneurysm size was 9.67±5.91 mm with a 4.31±1.97-mm neck . The most frequent sites were basilar bifurcation ( 27.7 % ) and carotid ophthalmic ( 18.0 % ) aneurysms . Recurrences were subjectively divided into minor and major ( ideally necessitating re-treatment ) . The most significant predictors of angiographic recurrence were determined by logistic regression . These results were confirmed by & khgr;2 , t tests , or ANOVAs followed , when appropriate , by Tukey ’s contrasts . Results — Short-term ( ≤1 year ) follow-up angiograms were available in 353 aneurysms ( 70.5 % ) and long-term ( > 1 year ) follow-up angiograms , in 277 ( 55 % ) , for a total of 383 ( 76.5 % ) followed up . Recurrences were found in 33.6 % of treated aneurysms that were followed up and that appeared at a mean±SD time of 12.31±11.33 months after treatment . Major recurrences presented in 20.7 % and appeared at a mean of 16.49±15.93 months . Three patients ( 0.8 % ) bled during a mean clinical follow-up period of 31.32±24.96 months . Variables determined to be significant predictors ( P < 0.05 ) of a recurrence included aneurysm size ≥10 mm , treatment during the acute phase of rupture , incomplete initial occlusions , and duration of follow-up . Conclusions — Long-term monitoring of patients treated by endosaccular coiling is m and atory BACKGROUND AND PURPOSE To prospect ively compare the effectiveness of time-of-flight ( TOF ) and contrast-enhanced ( CE ) MR angiography ( MRA ) with that of digital subtraction angiography ( DSA ) to assess immediate intracranial aneurysm occlusion after selective embolization . METHODS From August 2006 to March 2007 , 33 consecutive patients with 40 aneurysms were included . Thirty aneurysms were treated by endosaccular coils ( group 1 ) . Ten aneurysms were treated by stent placement and subsequent endosaccular coils ( group 2 ) . All patients underwent MRA within 24 h after treatment . One senior and one fellow radiologist independently review ed the MR images , and another senior radiologist review ed the DSA images . RESULTS DSA showed 22 complete occlusions , ten residual necks , and eight residual aneurysms . For residual neck detection , there was no difference between TOF-MRA ( sensitivity , 80%-80 % ; specificity , 93.8%-100 % , according to both readers ) and CE-MRA ( sensitivity , 80%-80 % ; specificity , 100 % ) . For residual aneurysm detection , there was a significant difference between TOF-MRA ( sensitivity , 50%-62.5 % ; specificity , 100 % ) and CE-MRA ( sensitivity and specificity , 100 % , according to both readers ) . In group 2 , a residual aneurysm was missed by both readers with TOF-MRA in the same 3 aneurysms . Moreover , both readers judged CE-MRA better than TOF-MRA to assess parent-artery patency in group 2 . Interobserver agreement was excellent for TOF-MRA and CE-MRA ( kappa=0.9 and 1 , respectively ) . CONCLUSIONS In our study , both TOF-MRA and CE-MRA had high and comparable sensitivity and specificity for the assessment of immediate aneurysm occlusion after selective embolization , except when a stent-assisted technique was used . In such cases , CE-MRA was superior to TOF-MRA to evaluate aneurysm occlusion and parent-artery patency PURPOSE The purpose of our study was to prospect ively evaluate 3D time-of-flight ( TOF ) MR angiography ( MRA ) in the follow-up of 27 intracranial aneurysms treated with Guglielmi detachable coils ( GDCs ) . METHOD From February 1997 to June 1998 , 26 patients with 27 aneurysms were included in this prospect i ve study . Aneurysms were located in the anterior circulation in 23 cases and in the posterior circulation in 4 cases . All patients underwent 3D TOF MRA and digital subtraction angiography ( DSA ) in the same week within 4 months after aneurysmal treatment with GDCs . No clinical events occurred during the follow-up . We analyzed residual flow within the coil mass and within the aneurysmal neck and the patency of the parent and adjacent arteries on MRA and DSA . MRA analysis was based upon MIPPED and source images . DSA was our gold st and ard . RESULTS In all cases , the quality of MRA was good enough to be informative . In aneurysmal analysis , the sensitivity , specificity , positive predictive value , and negative predictive value of MRA were , respectively , 80 , 100 , 100 , and 96 % to diagnose residual flow within the coil mass ( one false-negative case ) and 83 , 100 , 100 , and 95.5 % to diagnose residual flow within the aneurysmal neck ( one false-negative case ) . In arterial analysis , sensitivity and positive predictive value of MRA were 89 and 100 % to diagnose patency of the parent artery ( three false-negative cases ) and 83 and 100 % to diagnose patency of adjacent arteries ( seven false-negative cases ) . CONCLUSION In the follow-up of intracranial aneurysms treated with GDCs , 3D TOF MRA could be used as a screening test to select patients that should undergo DSA and thus could improve patient follow-up in terms of risk-benefit Introduction The purpose of this prospect i ve study was to compare 3 T and 1.5 T magnetic resonance angiography ( MRA ) with digital subtraction angiography ( DSA ) for the follow-up of endovascular treated intracranial aneurysms to assess the grade of occlusion . Material s and methods Thirty-seven patients with 41 aneurysms who had undergone endovascular treatment with detachable coils were included . MRA was performed on the same day using an eight-channel sensitivity encoding head-coil with 3D axial inflow technique . At 3 T , a contrast-enhanced transverse 3D fast gradient echo acquisition was also performed . Most patients underwent DSA the following day . MRA scans and DSA were classified first independently by two neuroradiologists and an interventional neuroradiologist . Secondly , a consensus was done . Source images , maximum intensity projection , multiplanar reconstruction and volume rendering reconstructions were used for MRA evaluations . A modification of the Raymond classification , previously used for DSA evaluation of recanalization , was used . Results Statistical comparison of the consensus showed that 3 T MRA with 3D axial inflow technique had better agreement with DSA ( κ = 0.43 ) than 1.5 T MRA(κ = 0.21 ) and contrast-enhanced MRA ( CE-MRA ) at 3 T ( κ = 0.17 ) . The susceptibility artefacts from the coil mesh were significally smaller at 3 T ( p = 0.002–0.007 ) than at 1.5 T . Conclusion 3 T MRA , using a sensitivity encoding head-coil , showed better agreement with DSA than 1.5 T and CE-MRA at 3 T for evaluation of aneurysms treated with endovascular coiling OBJECT Digital subtraction ( DS ) angiography is the current gold st and ard of assessing intracranial aneurysms after coil placement . Magnetic resonance ( MR ) angiography offers a noninvasive , low-risk alternative , but its accuracy in delineating coil-treated aneurysms remains uncertain . The objective of this study , therefore , is to compare a high-resolution MR angiography protocol relative to DS angiography for the evaluation of coil-treated aneurysms . METHODS In 2003 , the authors initiated a prospect i ve protocol of following up patients with coil-treated brain aneurysms using both 1.5-tesla gadolinium-enhanced MR angiography and biplanar DS angiography . Using acquired images , the subject aneurysm was independently scored for degree of remnant identified ( complete obliteration , residual neck , or residual aneurysm ) and the surgeon 's ability to visualize the parent vessel ( excellent , fair , or poor ) . RESULTS Thirty-seven patients with 42 coil-treated aneurysms were enrolled for a total of 44 paired MR angiography-DS angiography tests ( median 9 days between tests ) . An excellent correlation was found between DS and MR angiography for assessing any residual aneurysm , but not for visualizing the parent vessel ( K = 0.86 for residual aneurysm and 0.10 for parent vessel visualization ) . Paramagnetic artifact from the coil mass was minimal , and in some cases MR angiography identified contrast permeation into the coil mass not revealed by DS angiography . An intravascular microstent typically impeded proper visualization of the parent vessel on MR angiography . CONCLUSIONS Magnetic resonance angiography is a noninvasive and safe means of follow-up review for patients with coil-treated brain aneurysms . Compared with DS angiography , MR angiography accurately delineates residual aneurysm necks and parent vessel patency ( in the absence of a stent ) , and offers superior visualization of contrast filling within the coil mass . Use of MR angiography may obviate the need for routine diagnostic DS angiography in select patients PURPOSE To evaluate the safety and efficacy of endovascular treatment of ophthalmic segment aneurysms with Guglielmi detachable coils ( GDCs ) , as well as the primary indications for such treatment . METHODS We conducted a prospect i ve study of 26 patients with 28 aneurysms of the ophthalmic segment in whom treatment with GDCs was attempted . Anatomic results were measured by statistical analysis of variance for such factors as age , sex , presence of subarachnoid hemorrhage , anatomic type ( ophthalmic or superior hypophyseal ) , size of aneurysmal sac , and width of aneurysmal neck . Clinical evaluation and control angiography were performed at 6 and 18 months . RESULTS Overall , complete occlusion was obtained in 14 aneurysms ( 50 % ) and small residual necks were left in 11 aneurysms ( 39 % ) . Three treatment attempts failed ( 11 % ) . Complete occlusion was obtained in 76 % of small-necked aneurysms as opposed to 9 % of aneurysms with a large neck . The best predictor of anatomic result was the size of the aneurysmal neck . Complete occlusion was obtained in 85 % of superior hypophyseal aneurysms of the paraclinoid variant . One permanent complication was related to treatment . CONCLUSION Endovascular treatment with GDCs appears to be a safe and efficient alternative approach for ophthalmic segment aneurysms , especially for paraclinoid variants of superior hypophyseal aneurysms , which tend to have a small neck BACKGROUND AND PURPOSE The long-term outcome of patients treated with Guglielmi detachable coils ( GDCs ) remains unknown and is being evaluated . We sought to assess the feasibility and utility of contrast-enhanced MR angiography in the follow-up of anterior communicating artery ( AcomA ) aneurysms treated with GDCs . METHODS In a prospect i ve study , 20 consecutive patients with AcomA aneurysms underwent digital subtraction angiography ( DSA ) , time-of-flight MR angiography ( TOF-MRA ) , and contrast-enhanced MR angiography ( MRA ) 12 months after treatment with GDCs . The aneurysmal sac measured less than 10 mm in 19 patients and 12 mm in one patient . Two observers who did not analyze the DSA images independently review ed the MRA images . Aneurysms were classified according to the presence of a residual neck ( ie , complete occlusion , small residual neck , large residual neck , or not assessable ) . DSA was used as the st and ard of reference . RESULTS Images from all examinations were assessable . Venous enhancement was observed in five cases at contrast-enhanced MRA ; this did not affect image interpretation . Interobserver agreement was good . A comparison of the techniques showed good agreement in the detection of a residual neck . Two cases of a small residual neck were not detected at TOF-MRA , and one case of complete occlusion was misclassified as a small residual neck at contrast-enhanced MRA . CONCLUSION Our findings showed that contrast-enhanced MRA is a valuable method for the follow-up of aneurysms in the AcomA after their treatment with GDCs . Further studies with multiple aneurysm locations and larger groups are required to determine the exact role of this technique This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence BACKGROUND AND PURPOSE The aim of this study was to determine the feasibility and usefulness of contrast-enhanced MR angiography ( CE-MRA ) for the follow-up of intracranial aneurysms treated with detachable coils , by comparing CE-MRA with digital subtraction angiography ( DSA ) and 3D time-of- flight ( TOF ) MRA . METHODS Thirty-two patients with 42 treated aneurysms were included in the study ; 6 had been treated for multiple aneurysms . All MRAs were performed with a 1.5 T unit within 48 hours of DSA . We performed 2 types of acquisition : a 3D TOF sequence and CE-MRA . Twenty-eight patients were included 1 year after endovascular treatment , and 4 patients , after 3 years or more . DSA was the technique of reference for the detection of a residual neck or residual aneurysm . RESULTS Compared with DSA , the sensitivity of MRA was good . For the detection of residual neck , there was no significant difference between the results of 3D TOF MRA ( sensitivity , 75%-87.5 % ; specificity , 92.9 % , according to both readers ) and CE-MRA ( sensitivity , 75%-82.1 % ; specificity , 85.7%-92.9 % ) . For the detection of residual aneurysm , sensitivity and specificity of both techniques were the same , respectively 80%-100 % and 97.3%-100 % . Therefore , CE-MRA was not better than 3D TOF MRA for the detection of residual neck or residual aneurysm . For large treated aneurysms , there was no difference between decisions regarding further therapy after CE and 3D TOF MRA , even though CE-MRA with a short echotime and enhancement gave fewer artifacts and better visualization of recanalization than 3D TOF MRA . The interpretation of transverse source images and the detection of coil mesh packing seemed easier with 3D TOF imaging . CONCLUSION This prospect i ve study did not show that CE-MRA was significantly better than 3D TOF MRA for depicting aneurysm or neck remnants after selective endovascular treatment using coils . For aneurysms treated with coils , 3D TOF MRA seems a valid and useful technique for the follow-up of coiled aneurysms BACKGROUND AND PURPOSE Although digital subtraction angiography ( DSA ) is considered the criterion st and ard for depiction of intracranial aneurysms , it is often difficult to determine the relationship of overlapping vessels to aneurysms when using 2D DSA . We compared 2D and 3D DSA in evaluation of intracranial aneurysms . METHODS Thirty-six consecutive patients with cerebral aneurysms underwent 2D and 3D DSA . After st and ard 2D DSA , rotational DSA was performed . Maximum intensity projection ( MIP ) and shaded surface display ( SSD ) images were created from the rotational DSA data sets . All images were assessed r and omly for overall image quality , presence of aneurysm , presence of aneurysmal lobulation , visualization of aneurysmal neck , and relationship to adjacent vessels . Data analysis was conducted for 40 aneurysms treated by clip placement . RESULTS One aneurysm that was not detected at 2D DSA was classified as uncertain on the basis of rotational DSA . All aneurysms were classified as probably or definitively present on the basis of MIP and SSD findings . Overall image quality of rotational DSA , MIP , and SSD was statistically inferior to that of the st and ard 2D DSA for visualization of distal arteries . However , MIP and SSD images were significantly superior to those of st and ard 2D DSA for all other evaluations . For detection of lobulation , SSD images were significantly superior to other images , and for visualization of aneurysmal neck and relationship to neighboring arteries , SSD images were significantly superior to those of rotational DSA . For evaluation of the relationship to neighboring arteries , MIP images were significantly superior to those of rotational DSA . CONCLUSION Three-dimensional DSA , especially SSD , provided more detailed information for evaluating cerebral aneurysms than did st and ard 2D and rotational DSA BACKGROUND AND PURPOSE Three-dimensional time-of-flight ( TOF ) MR angiography has been evaluated in the follow-up of intracranial aneurysms treated with Guglielmi detachable coils ( GDCs ) with good results . Some of the studies used contrast material in addition to the 3D TOF MR technique and others did not . We assessed the usefulness of contrast material with 3D TOF MR angiography by comparing this sequence before and after contrast material injection . METHODS Fifty-eight patients harboring a total of 71 cerebral aneurysms previously treated with GDCs were included in the prospect i ve study . MR angiography ( at 1.5 T ) was performed with a 3D TOF sequence before and after injection of gadolinium-based contrast material . Features evaluated were presence and size of a neck remnant , parent and adjacent vessel patency , and venous overlap . Digital subtraction angiography was the st and ard of reference . RESULTS Comparison of the techniques showed a good agreement in the detection of residual flow . Six cases of small residual neck were not detected with either the 3D TOF or the contrast-enhanced 3D TOF sequence . In one case of giant aneurysm , the extent of recanalization was more evident after contrast material administration . The use of contrast material did not help to show the parent and adjacent arteries . Venous overlap on contrast-enhanced 3D TOF angiograms did not affect image interpretation . CONCLUSION In this series , the use of intravenous contrast material did not improve the ability of 3D TOF MR angiography to depict the presence of residual or recurrent aneurysms previously treated with endovascular coiling . In one giant aneurysm , use of intravenous contrast material did result in improved visualization of a residual aneurysm OBJECTIVE To compare 3D time-of-flight MR angiography ( TOF-MRA ) at 3 Tesla ( 3 T ) with digital subtraction angiography ( DSA ) for the evaluation of intracranial aneurysm occlusion after endovascular coiling . METHODS In a prospect i ve study , 51 consecutive patients ( 25 females , 26 males ; median age , 51 years ) with 51 saccular aneurysms treated with endovascular coiling underwent simultaneous DSA and 3 T TOF-MRA at follow-up . DSA and TOF-MRA images were analyzed independently by two senior neuroradiologists . Findings were assigned to 1 of 3 categories in the Raymond classification : complete obliteration , residual neck or residual aneurysm . Agreement between observers and techniques was evaluated using kappa statistics . RESULTS DSA images were not interpretable for one patient . Interobserver agreement was determined as excellent for DSA ( kappa=0.86 ) and TOF-MRA ( kappa=0.80 ) . After reaching a consensus , DSA follow-up showed 26 ( 51 % ) complete obliterations , 20 ( 39 % ) residual necks and 4 ( 8 % ) residual aneurysms . TOF-MRA showed 23 ( 45 % ) complete obliterations , 22 ( 43 % ) residual necks and 6 ( 12 % ) residual aneurysms . Comparison between TOF-MRA and DSA showed excellent agreement between the techniques ( kappa=0.86 ) . In the four cases that were misclassified , TOF-MRA findings were assigned to a higher class than for DSA . CONCLUSION TOF-MRA at 3 T is at least as efficient as DSA for the evaluation of intracranial aneurysm occlusion after endovascular treatment with detachable coils . We suggest that TOF-MRA at 3 T might be used as the primary method for imaging follow-up of coiled intracranial aneurysms Background : Digital subtraction angiography ( DSA ) is still regarded as the gold st and ard for detecting residual flow in treated aneurysms . Recent reports have also shown excellent results from magnetic resonance angiography ( MRA ) imaging . This is an important observation , since DSA is associated with a risk of medical complications , is time consuming , and is more expensive . Purpose : To determine whether MRA could replace conventional DSA and serve as the primary postinterventional imaging modality in patients with coiled intracranial aneurysms . Material and Methods : We studied a prospect ively enrolled cohort of 190 patients treated endovascularly for a first-ruptured and /or unruptured intracranial aneurysm between January 2004 and December 2008 . The imaging protocol included a 1.5 T time-of-flight ( TOF ) MRA and a DSA at 3 months ( on the same day ) and , depending on comparability , a 1.5 T TOF-MRA or DSA 1 year after treatment . All images were evaluated by a multidisciplinary panel . Results : In 141/190 patients , both an MRA and DSA were performed after 3-month follow-up . In 2/141 patients ( 1.4 % ) , ( small ) neck remnants gave false-negative MRA results . In one patient ( 0.7 % ) , this led to additional neurosurgical clipping of the aneurysm . In 25/141 patients , future follow-up ( > 3 months ) consisted of DSA because of various reasons . In 24/25 of these patients , primary MRA images alone would invariably have led to additional DSA imaging . Conclusion : The present study shows that 1.5 T TOF-MRA is a feasible primary follow-up modality after coiling of intracranial aneurysms . Given our data , we now suggest that , in every patient with a coiled intracranial aneurysm , the first follow-up , 3 months after coiling , should be an MRA study . Only when this MRA is inconclusive ( e.g. , because of coil artifacts ) , or in the case of suspicion of recanalization , should DSA be performed additionally BACKGROUND Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms , although the relative benefits of these two approaches have yet to be established . We undertook a r and omised , multicentre trial to compare the safety and efficacy of endovascular coiling with st and ard neurosurgical clipping for such aneurysms judged to be suitable for both treatments . METHODS We enrolled 2143 patients with ruptured intracranial aneurysms and r and omly assigned them to neurosurgical clipping ( n=1070 ) or endovascular treatment by detachable platinum coils ( n=1073 ) . Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death . The primary outcome was the proportion of patients with a modified Rankin scale score of 3 - 6 ( dependency or death ) at 1 year . Trial recruitment was stopped by the steering committee after a planned interim analysis . Analysis was per protocol . FINDINGS 190 of 801 ( 23.7 % ) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 ( 30.6 % ) allocated neurosurgical treatment ( p=0.0019 ) . The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6 % ( 95 % CI 8.9 - 34.2 ) and 6.9 % ( 2.5 - 11.3 ) , respectively . The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment , respectively . INTERPRETATION In patients with a ruptured intracranial aneurysm , for which endovascular coiling and neurosurgical clipping are therapeutic options , the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling . The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy , although somewhat more frequent with endovascular coiling BACKGROUND AND PURPOSE : Endovascularly coiled intracranial aneurysms are increasingly being followed up with noninvasive MRA imaging to evaluate for aneurysm recurrences . It has not been well-established which MRA techniques are best for this application , however . Our aim was to prospect ively compare 4 MRA techniques , TOF and CE-MRA at 1.5 T and 3 T , to a reference st and ard of DSA in the evaluation of previously endovascularly coiled intracranial aneurysms . MATERIAL S AND METHODS : Fifty-eight subjects with 63 previously coiled intracranial aneurysms underwent all 4 MRA techniques within 8 days of DSA . There were 2 outcome variables : coil occlusion class ( class 1 , complete ; class 2 , dog ear ; class 3 , residual neck ; class 4 , aneurysm filling ) and change in degree of occlusion since the previous comparison . Sensitivity and specificity were computed for each MRA technique relative to the reference st and ard of DSA . Differences among the MRA techniques were evaluated in pair-wise fashion by using the McNemar test . RESULTS : For the detection of any aneurysm remnant , the sensitivity was 85%–90 % for all MRA techniques . Sensitivity dropped to 50%–67 % when calculated for the detection of only the class 3 and 4 aneurysm remnants , because several class 3 and 4 remnants were misclassified as class 2 by MRA . CE-MRA at 1.5 T and 3 T misclassified fewer of the class 3 and 4 remnants than did TOF-MRA at 1.5 T , as reflected by the significantly greater sensitivity for larger aneurysm remnants with CE-MRA relative to TOF-MRA at 1.5 T ( P = .0455 for both comparisons ) . CONCLUSIONS : CE-MRA is more likely than TOF-MRA to classify larger aneurysm remnants appropriately . We recommend performing both CE-MRA and TOF-MRA in the follow-up of coiled intracranial aneurysms and at 3 T if available BACKGROUND AND PURPOSE : Catheter angiography has been the criterion st and ard for follow-up evaluation of coiled intracranial aneurysms . In our center , CE-MRA has been used to evaluate aneurysm recanalization . Our aim was to investigate the feasibility and usefulness of a CE-MRA protocol for following patients with intracranial aneurysms treated with endovascular coiling . MATERIAL S AND METHODS : From September 2003 to December 2006 , 134 aneurysms were treated by endovascular coiling in 124 patients by using detachable coils . These patients were followed with CE-MRA at 3 months , 15 months , and 3 and 5 years . MRAs were analyzed by 2 interventional neuroradiologists . Findings were assigned to 3 categories : complete obliteration ( class 1 ) , residual neck ( class 2 ) , and residual aneurysm ( class 3 ) . RESULTS : Initially , CE-MRA demonstrated 67 ( 50 % ) complete obliterations ( class 1 ) , 57 ( 41.79 % ) residual necks ( class 2 ) , and 8 ( 5.97 % ) residual aneurysms ( class 3 ) . No patient experienced rebleed during the follow-up period . A total of 214 patient-years of follow-up were obtained ( range , 0–53 months ) . Two ( 1.49 % ) patients died after the follow-up , and 11 ( 8.21 % ) patients were lost to follow-up . On follow-up , 76 ( 56.72 % ) patients showed stable results . Fifty-six ( 41.79 % ) aneurysms showed change in their obliteration pattern . Of these 56 , 47 demonstrated recanalization and 9 ( 6.72 % ) showed further obliteration . Most of the aneurysms that showed change in their obliteration remained stable on follow-up . Only 11 ( 8.21 % of the total and 23.4 % of those who showed recanalization ) patients underwent recoiling or clipping . CONCLUSIONS : CE-MRA can be used in routine practice to follow-up aneurysm recanalization noninvasively . CE-MRA permits close-interval follow-up and may show more filling of the aneurysm neck or sac than DSA OBJECT The aim of this study was to assess the long-term results of intracranial aneurysms treated with Guglielmi detachable coils ( GDCs ) with the aid of contrast-enhanced magnetic resonance ( MR ) angiography . METHODS Between January 1998 and August 2001 , 92 patients with 92 aneurysms treated by endovascular coiling with GDCs underwent contrast-enhanced MR angiography . These patients underwent long-term follow-up ( range 32 - 78 months , mean 42.1 + /- 11.9 months [ st and ard deviation ] ) after endovascular treatment . All images were compared with digital subtraction angiograms and contrast-enhanced MR angiograms that had been obtained during the short-term follow-up ( range 5 - 25 months , mean 13 + /- 5.1 months after treatment ) . The MR angiograms were analyzed independently by 2 senior radiologists . Findings were assigned to 1 of 3 categories : complete obliteration ( Class 1 ) , residual neck ( Class 2 ) , or residual aneurysm ( Class 3 ) . RESULTS Of 92 contrast-enhanced MR angiograms obtained at the long-term follow-up , complete obliteration of the aneurysm was noted in 57 patients ( Class 1 ) , a residual neck was seen in 22 ( Class 2 ) , and a residual aneurysm was observed in 13 ( Class 3 ) . One patient experienced aneurysm rehemorrhaging during the follow-up period . The comparison of short- and long-term follow-up angiograms demonstrated a change in aneurysm classification in 7 patients ( 7.6 % ) , including 4 that progressed from Class 1 to Class 2 and 3 from Class 2 to Class 3 . However , 4 ( 14.2 % ) of the 28 long-term recurrences were not detected on the short-term control images . CONCLUSIONS Long-term follow-up with contrast-enhanced MR angiography after selective embolization of intracranial aneurysms can identify late aneurysm recanalization that is undetected at short-term follow-up Background : Contrast-enhanced magnetic resonance angiography ( CE-MRA ) is less prone to flow-related signal intensity loss than three-dimensional time-of-flight ( 3D TOF ) MRA and may therefore be more sensitive for detection of residual patency in platinum coil-treated intracranial aneurysms . Purpose : To compare MRA and CE-MRA in the follow-up of intracranial aneurysms treated with platinum coils . Material and Methods : CE-MRA and 3D TOF MRA ( pre- and postcontrast injection ) of the intracranial vasculature was performed at 1.5 T in 38 patients ( 47 aneurysms ) referred for DSA in the follow-up of coiled intracranial aneurysms . Results : DSA showed aneurysm patency in 22/47 investigations . Patent aneurysm components were observed with CE-MRA in 18/22 cases , and with 3D TOF MRA in 21/22 cases . There was no significant difference in patent aneurysm component size between CE-MRA and 3D TOF MRA . In addition , CE-MRA showed six , 3D TOF MRA before contrast injection showed seven , and 3D TOF MRA after contrast injection showed eight cases with patent aneurysm components not observed on DSA . Conclusion : 3D TOF MRA was highly sensitive for detection of patent aneurysm components , and at least as sensitive as CE-MRA . Residual aneurysm patency seems to be better visualized with MRA than with DSA in some cases Introduction Cerebral angiography is an invasive procedure associated with a small , but definite risk of neurological morbidity . In this study we sought to establish the nature and rate of complications at our institution among a large prospect i ve cohort of consecutive patients . Also , the data were analysed in an attempt to identify risk factors for complications associated with catheter angiography . Methods Data were prospect ively collected for a consecutive cohort of patients undergoing diagnostic cerebral angiography between January 2001 and May 2006 . A total of 2,924 diagnostic cerebral angiography procedures were performed during this period . The following data were recorded for each procedure : date of procedure , patient age and sex , clinical indication , referring specialty , referral status ( routine/emergency ) , operator , angiographic findings , and the nature of any clinical complication or asymptomatic adverse event ( arterial dissection ) . Results Clinical complications occurred in 23 ( 0.79 % ) of the angiographic procedures : 12 ( 0.41 % ) significant puncture-site haematomas , 10 ( 0.34 % ) transient neurological events , and 1 nonfatal reaction to contrast agent . There were no permanent neurological complications . Asymptomatic technical complications occurred in 13 ( 0.44 % ) of the angiographic procedures : 3 groin dissections and 10 dissections of the cervical vessels . No patient with a neck dissection suffered an immediate or delayed stroke . Emergency procedures ( P = 0.0004 ) and angiography procedures performed for intracerebral haemorrhage ( P = 0.02 ) and subarachnoid haemorrhage ( P = 0.04 ) were associated with an increased risk of complications . Conclusion Neurological complications following cerebral angiography are rare ( 0.34 % ) , but must be minimized by careful case selection and the prudent use of alternative noninvasive angiographic techniques , particularly in the acute setting . The low complication rate in this series was largely due to the favourable case mix PURPOSE To compare three-dimensional ( 3D ) time-of-flight magnetic resonance ( MR ) angiography with digital subtraction angiography ( DSA ) in the follow-up of intracranial aneurysms treated with selective endovascular placement of detachable coils . MATERIAL S AND METHODS Sixty-eight consecutive patients with intracranial aneurysms were included in the prospect i ve study . The goal was to evaluate 3D time-of-flight MR angiography versus DSA for the detection of a residual aneurysm neck or residual flow inside the coil mesh . RESULTS Eighty-one MR angiographic and 83 DSA examinations were performed ; 15 patients were examined with both modalities twice . MR angiography was not possible in two patients . In another patient , the quality of MR angiography was not sufficient to assess the treated aneurysm . In 72 of the remaining 80 MR angiographic and DSA examinations , there was good correlation between the two modalities . In 54 cases , neither image type showed remnants or recurrence , but in 18 , both showed residual aneurysm . In eight cases , the MR angiographic and DSA results differed . In one of these cases , MR angiography depicted residual aneurysm but DSA depicted an arterial loop . In seven cases , a small ( < 3-mm ) remnant was not detected at MR angiography . CONCLUSION Because very small aneurysm remnants or recurrences probably are not clinical ly important , MR angiography is an option for following up intracranial aneurysms treated with detachable coils and may partly replace DSA All patients with aneurysms treated with Guglielmi detachable coils ( GDC ) are undergo angiography to assess long-term stability of aneurysm exclusion or to show recurrence of the aneurysm sac , which may require further treatment . We prospect ively compared the plain-film appearance of the coil-mass , 3D time-of-flight MR angiography ( TOF MRA ) and digital subtraction angiography ( DSA ) for the detection of aneurysm recanalisation during follow-up . We studied 60 patients with 74 intracranial aneurysms treated with Guglielmi detachable coils . We used the unsubtracted image of the angiograms performed at the completion of any embolisation procedure and at follow-up as the plain radiographs . Recanalisation was considered if loosening , compaction or reorientation of the coil mass was apparent . TOF MRA was performed to assess the presence and size of a neck remnant . DSA was regarded as the definitive investigation . Comparison of the techniques showed good agreement as regards aneurysm recanalisation . MRA was more accurate than plain radiography and could replace DSA for long term follow- up . The initial follow-up examination should , however , include both modalities . In cases of contraindications or limitations to MRA , the interval between follow-up angiographic examinations could be increased if there is no change in the plain-film coil-mass appearances BACKGROUND AND PURPOSE The purpose of this study was to assess the incidence of de novo aneurysm formation , the incidence of subarachnoid hemorrhage ( SAH ) , and the growth of existing untreated aneurysms in 52 patients after therapeutic carotid artery balloon occlusion for carotid aneurysms . PATIENTS AND METHODS Between January 1996 and August 2004 , 52 patients were treated with carotid artery balloon occlusion for carotid aneurysms . In June 2005 , all patients , their next of kin , or family physicians were contacted and question ed concerning episodes of headache or hospital admissions that could be attributed to SAH . In addition , MR imaging and MR angiography ( MRA ) at 3 T were performed in 26 of 44 surviving patients after a mean follow-up period of 50.2 months ( median , 43.5 months ; range , 14 - 107 months ) . MR imaging and MRA studies were compared with the digital subtraction angiograms at the time of carotid artery occlusion . RESULTS During clinical follow-up of 52 patients at a mean of 50.3 months ( median , 42.5 months ; range , 0 - 107 months ) , no episodes of SAH were reported ( 0 % ; 97.5 % confidence interval [ CI ] , 0 - 8.2 % ) . In the 26 patients with follow-up MR imaging , no de novo aneurysms were detected ( 0 % ; 97.5 CI , 0 - 13.2 % ) . Five existing untreated small aneurysms in 5 patients had not enlarged after a mean follow-up of 40 months . CONCLUSION In this study , therapeutic carotid artery occlusion was not associated with development of new aneurysms or enlargement of existing untreated aneurysms with time Time-of-flight magnetic resonance angiography is a non-invasive alternative to digital subtraction angiography ( DSA ) for follow up of coiled intracranial aneurysms . St and ard cranial MRA protocol s are a compromise between spatial resolution and imaging time . This study compares a st and ard resolution MRA protocol with a protocol at higher spatial resolution MRA ( HR-MRA ) in 21 follow-up occasions in 17 coiled aneurysms in 15 patients . Images were review ed for presence of residual or recurrent aneurysm and compared with DSA as the gold st and ard . Aneurysm flow signal on st and ard resolution MRA differed significantly from HR-MRA in 6/21 cases ( P = 0.02 ) and DSA in 6/21 cases ( P = 0.02 ) . HR-MRA had 100 % concordance with DSA ( P = 1.0 ) . In this study , three-dimensional time-of-flight magnetic resonance angiography carried out at st and ard resolution is inadequate for follow up of coiled intracranial aneurysms . HR-MRA is comparable to DSA for detection of aneurysm recurrence |
2,199 | 18,331,422 | The meta- analysis shows a moderate association between obesity and the risks for dementia and AD . | While dementia affects 6 - 10 % of persons 65 years or older , industrialized countries have witnessed an alarming rise in obesity .
However , obesity 's influence on dementia remains poorly understood . | BACKGROUND Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies , but there is limited study of whether this type of fat protects against Alzheimer disease . OBJECTIVE To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease . DESIGN Prospect i ve study conducted from 1993 through 2000 , of a stratified r and om sample from a geographically defined community . Participants were followed up for an average of 3.9 years for the development of Alzheimer disease . PATIENTS A total of 815 residents , aged 65 to 94 years , who were initially unaffected by Alzheimer disease and completed a dietary question naire on average 2.3 years before clinical evaluation of incident disease . MAIN OUTCOME MEASURES Incident Alzheimer disease diagnosed in a structured neurologic examination by means of st and ardized criteria . RESULTS A total of 131 sample participants developed Alzheimer disease . Participants who consumed fish once per week or more had 60 % less risk of Alzheimer disease compared with those who rarely or never ate fish ( relative risk , 0.4 ; 95 % confidence interval , 0.2 - 0.9 ) in a model adjusted for age and other risk factors . Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease , as was intake of docosahexaenoic acid ( 22:6n-3 ) . Eicosapentaenoic acid ( 20:5n-3 ) was not associated with Alzheimer disease . The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions . CONCLUSION Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease BACKGROUND Participation in leisure activities has been associated with a lower risk of dementia . It is unclear whether increased participation in leisure activities lowers the risk of dementia or participation in leisure activities declines during the pre clinical phase of dementia . METHODS We examined the relation between leisure activities and the risk of dementia in a prospect i ve cohort of 469 subjects older than 75 years of age who resided in the community and did not have dementia at base line . We examined the frequency of participation in leisure activities at enrollment and derived cognitive-activity and physical-activity scales in which the units of measure were activity-days per week . Cox proportional-hazards analysis was used to evaluate the risk of dementia according to the base-line level of participation in leisure activities , with adjustment for age , sex , educational level , presence or absence of chronic medical illnesses , and base-line cognitive status . RESULTS Over a median follow-up period of 5.1 years , dementia developed in 124 subjects ( Alzheimer 's disease in 61 subjects , vascular dementia in 30 , mixed dementia in 25 , and other types of dementia in 8) . Among leisure activities , reading , playing board games , playing musical instruments , and dancing were associated with a reduced risk of dementia . A one-point increment in the cognitive-activity score was significantly associated with a reduced risk of dementia ( hazard ratio , 0.93 [ 95 percent confidence interval , 0.90 to 0.97 ] ) , but a one-point increment in the physical-activity score was not ( hazard ratio , 1.00 ) . The association with the cognitive-activity score persisted after the exclusion of the subjects with possible pre clinical dementia at base line . Results were similar for Alzheimer 's disease and vascular dementia . In linear mixed models , increased participation in cognitive activities at base line was associated with reduced rates of decline in memory . CONCLUSIONS Participation in leisure activities is associated with a reduced risk of dementia , even after adjustment for base-line cognitive status and after the exclusion of subjects with possible pre clinical dementia . Controlled trials are needed to assess the protective effect of cognitive leisure activities on the risk of dementia CONTEXT Exogenous estrogen use may lower risk of dementia in postmenopausal women . A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied . OBJECTIVE To determine whether a longer reproductive period , as an indicator of longer exposure to endogenous estrogens , is associated with lower risk of dementia and Alzheimer disease ( AD ) in women who have natural menopause . DESIGN AND SETTING The Rotterdam Study , a population -based prospect i ve cohort study conducted in the Netherl and s. PARTICIPANTS A total of 3601 women aged 55 years or older who did not have dementia at baseline ( 1990 - 1993 ) and had information on age at menarche , age at menopause , and type of menopause . Participants were reexamined in 1993 - 1994 and 1997 - 1999 and were continuously monitored for development of dementia . MAIN OUTCOME MEASURES Incidence of dementia , based on Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition criteria , and AD , based on National Institute of Neurological Disorders and Stroke/Alzheimer 's Disease and Related Disorders Association criteria , compared by quartiles of reproductive period among women with natural menopause . RESULTS During 21 046 person-years of follow-up ( median follow-up , 6.3 years ) , 199 women developed dementia , including 159 who developed AD . After adjusting for age , dementia was not clearly associated with length of reproductive period . However , after adjusting for multiple covariates , women with natural menopause and more reproductive years had an increased risk of dementia ( adjusted rate ratio [ RR ] for women with > 39 reproductive years [ highest quartile ] compared with < 34 reproductive years [ lowest quartile ] , 1.78 ; 95 % confidence interval [ CI ] , 1.12 - 2.84 ) . The adjusted RR per year of increase was 1.04 ( 95 % CI , 1.01 - 1.08 ) . For risk of AD , the adjusted RRs were 1.51 ( 95 % CI , 0.91 - 2.50 ) and 1.03 ( 95 % CI , 1.00 - 1.07 ) , respectively . Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers ( adjusted RR for > 39 reproductive years compared with < 34 reproductive years , 4.20 [ 95 % CI , 1.97 - 8.92 ] for dementia and 3.42 [ 95 % CI , 1.51 - 7.75 ] for AD ) , whereas in noncarriers , no clear association with dementia or AD was observed . CONCLUSION Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause BACKGROUND Few prospect i ve studies have assessed diabetes mellitus as a risk factor for incident Alzheimer disease ( AD ) and decline in cognitive function . OBJECTIVE To evaluate the association of diabetes mellitus with risk of AD and change in different cognitive systems . DESIGN Longitudinal cohort study . PARTICIPANTS For up to 9 years , 824 older ( those > 55 years ) Catholic nuns , priests , and brothers underwent detailed annual clinical evaluations . MAIN OUTCOME MEASURES Clinical ly diagnosed AD and change in global and specific measures of cognitive function . RESULTS Diabetes mellitus was present in 127 ( 15.4 % ) of the participants . During a mean of 5.5 years of observation , 151 persons developed AD . In a proportional hazards model adjusted for age , sex , and educational level , those with diabetes mellitus had a 65 % increase in the risk of developing AD compared with those without diabetes mellitus ( hazard ratio , 1.65 ; 95 % confidence interval , 1.10 - 2.47 ) . In r and om effects models , diabetes mellitus was associated with lower levels of global cognition , episodic memory , semantic memory , working memory , and visuospatial ability at baseline . Diabetes mellitus was associated with a 44 % greater rate of decline in perceptual speed ( P = .02 ) , but not in other cognitive systems . CONCLUSIONS Diabetes mellitus may be associated with an increased risk of developing AD and may affect cognitive systems differentially Objective To investigate whether plasma interleukin-6 ( IL-6 ) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population -based sample of nondisabled elderly people . Methods A prospect i ve cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted . Regression modeling was used to investigate whether baseline IL-6 levels ( classified by tertiles ) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 ( 2.5-year follow-up ) and from 1988 to 1995 ( 7-year follow-up ) . Results Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function ( i.e. , scores below the median ) , independent of demographic status , social status , health and health behaviors , and other physiologic variables ( odds ratio [ OR ] = 1.46 ; 95 % CI : 0.97 , 2.20 ) . At 2.5 years , those in both the second tertile of IL-6 ( OR = 2.21 ; 95 % CI : 1.44 , 3.42 ) and the third tertile ( OR = 2.03 ; 95 % CI : 1.30 , 3.19 ) were at increased risk of cognitive decline even after adjusting for all confounders . At 7 years of follow-up , only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition ( OR = 1.90 ; 95 % CI : 1.14 , 3.18 ) after adjustment for all confounders . Conclusions The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function . These findings are consistent with the hypothesized relationship between brain inflammation , as measured here by elevated plasma IL-6 , and neuropathologic disorders Background : Moderate alcohol drinking is suggested to be beneficial for cognitive functions , but the results of previous studies have varied greatly . Little is known about the effects of midlife alcohol drinking on the cognitive functions later in life . Methods : Participants were derived from r and om , population -based sample s studied in Eastern Finl and in 1972 , 1977 , 1982 , or 1987 . A total of 1,341 participants were reexamined in 1998 , after an average follow-up period of 21 years , at ages 65–79 years . Results : The participants who did not drink alcohol at midlife had a poorer performance in episodic memory , psychomotor speed , and executive function in late life as compared with infrequent and frequent drinkers , adjusted for sociodemographic and vascular factors . Also late-life nondrinkers had poorer psychomotor speed and executive function . These findings were evident especially among nonsmokers . Further , no interactions between apolipoprotein E4 and alcohol or sex and alcohol were found . Conclusions : Alcohol drinking both at midlife and later is favorably related to the function in several cognitive domains , including episodic memory , psychomotor speed , and executive function , in late life . However , it is not clear whether the association is causal , what is the possible mechanism , and what would be a safe limit of drinking for the best cognitive function Although many studies have found a cross-sectional relation between depression and dementia or depressive symptomatology and cognitive functioning , the direction of the association is still unknown . The purpose of this analysis was to determine whether high depressive symptomatology is predictive of cognitive deterioration among the elderly 3 years later . Data came from a community-based prospect i ve cohort study of noninstitutionalized and nondemented subjects aged 65 years and over living in the Gironde department in southwest France ( 1,600 subjects were interviewed at both study entry in 1989 and 3-year follow-up ) . Cognitive functions were assessed with the Mini-Mental State Examination ( MMSE ) , and cognitive deterioration was defined as an MMSE score decrease of at least five points between two assessment s. The Center for Epidemiologic Studies Depression ( CES-D ) Scale was used to evaluate the level of depressive symptomatology . The present study reports that a high level of depressive symptomatology is not predictive of cognitive deterioration 3 years later ( relative risk = 0.8 , 95 % confidence interval 0.3 - 2.1 ) . The authors observed that the risk of cognitive deterioration was associated with the concomitant level of depressive symptomatology at the 3-year follow-up , independent of depressive symptoms at entry . These results indicate that the association between high depressive symptomatology and poor cognitive functioning is cross-sectional , and they illustrate the importance of adjusting for depressive symptomatology in epidemiologic studies assessing cognitive functions Studies of disability in old age have focused on gross measures of physical functioning . More useful results for prevention might be gleaned from examining risk factors associated with frailty , a concept implying a broader range of more subtle problems in multiple domains . This study conceptualized frailty as involving problems or difficulties in two or more functional domains ( physical , nutritive , cognitive , and sensory ) and analyzed prospect i ve predictors . Subjects were 574 Alameda County Study respondents age 65 - 102 . One-fourth scored as frail ; there was no gender difference . Frail persons reported reduced activities , poorer mental health , and lower life satisfaction . Cumulative predictors over the previous three decades included heavy drinking , cigarette smoking , physical inactivity , depression , social isolation , fair or poor perceived health , prevalence of chronic symptoms , and prevalence of chronic conditions . By modifying these risk factors , it may be possible to postpone the onset of frailty or ameliorate its further development Abstract Objective To evaluate any association between obesity in middle age , measured by body mass index and skinfold thickness , and risk of dementia later in life . Design Analysis of prospect i ve data from a multiethnic population based cohort . Setting Kaiser Permanente Northern California Medical Group , a healthcare delivery organisation . Participants 10 276 men and women who underwent detailed health evaluations from 1964 to 1973 when they were aged 40 - 45 and who were still members of the health plan in 1994 . Main outcome measures Diagnosis of dementia from January 1994 to April 2003 . Time to diagnosis was analysed with Cox proportional hazard models adjusted for age , sex , race , education , smoking , alcohol use , marital status , diabetes , hypertension , hyperlipidaemia , stroke , and ischaemic heart disease . Results Dementia was diagnosed in 713 ( 6.9 % ) participants . Obese people ( body mass index ≥ 30 ) had a 74 % increased risk of dementia ( hazard ratio 1.74 , 95 % confidence interval 1.34 to 2.26 ) , while overweight people ( body mass index 25.0 - 29.9 ) had a 35 % greater risk of dementia ( 1.35 , 1.14 to 1.60 ) compared with those of normal weight ( body mass index 18.6 - 24.9 ) . Compared with those in the lowest fifth , men and women in the highest fifth of the distribution of subscapular or tricep skinfold thickness had a 72 % and 59 % greater risk of dementia , respectively ( 1.72 , 1.36 to 2.18 , and 1.59 , 1.24 to 2.04 ) . Conclusions Obesity in middle age increases the risk of future dementia independently of comorbid conditions CONTEXT Dementia is common , costly , and highly age related . Little attention has been paid to the identification of modifiable lifestyle habits for its prevention . OBJECTIVE To explore the association between physical activity and the risk of cognitive impairment and dementia . DESIGN , SETTING , AND SUBJECTS Data come from a community sample of 9008 r and omly selected men and women 65 years or older , who were evaluated in the 1991 - 1992 Canadian Study of Health and Aging , a prospect i ve cohort study of dementia . Of the 6434 eligible subjects who were cognitively normal at baseline , 4615 completed a 5-year follow-up . Screening and clinical evaluations were done at both waves of the study . In 1996 - 1997 , 3894 remained without cognitive impairment , 436 were diagnosed as having cognitive impairment-no dementia , and 285 were diagnosed as having dementia . MAIN OUTCOME MEASURE Incident cognitive impairment and dementia by levels of physical activity at baseline . RESULTS Compared with no exercise , physical activity was associated with lower risks of cognitive impairment , Alzheimer disease , and dementia of any type . Significant trends for increased protection with greater physical activity were observed . High levels of physical activity were associated with reduced risks of cognitive impairment ( age- , sex- , and education-adjusted odds ratio , 0.58 ; 95 % confidence interval , 0.41 - 0.83 ) , Alzheimer disease ( odds ratio , 0.50 ; 95 % confidence interval , 0.28 - 0.90 ) , and dementia of any type ( odds ratio , 0.63 ; 95 % confidence interval , 0.40 - 0.98 ) . CONCLUSION Regular physical activity could represent an important and potent protective factor for cognitive decline and dementia in elderly persons CONTEXT Oxidative processes have been suggested as elements in the development of Alzheimer disease ( AD ) , but whether dietary intake of vitamin E and other antioxidant nutrients prevents its development is unknown . OBJECTIVE To examine whether intake of antioxidant nutrients , vitamin E , vitamin C , and beta carotene is associated with incident AD . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study , conducted from 1993 to 2000 , of individuals selected in a stratified r and om sample of community-dwelling residents . The 815 residents 65 years and older were free of AD at baseline and were followed up for a mean of 3.9 years . They completed food frequency question naires an average of 1.7 years after baseline . MAIN OUTCOME MEASURE Incident AD diagnosed in clinical evaluations with st and ardized criteria . RESULTS Increasing vitamin E intake from foods was associated with decreased risk of developing AD after adjustment for age , education , sex , race , APOE epsilon 4 , and length of follow-up . Relative risks ( 95 % confidence intervals [ CIs ] ) from lowest to highest quintiles of intake were 1.00 , 0.71 ( 0.24 - 2.07 ) , 0.62 ( 0.26 - 1.45 ) , 0.71 ( 0.27 - 1.88 ) , and 0.30 ( 0.10 - 0.92 ) ( P for trend = .05 ) . The protective association of vitamin E was observed only among persons who were APOE epsilon 4 negative . Adjustment for other dietary factors reduced the protective association . After adjustment for baseline memory score , the risk was 0.36 ( 95 % CI , 0.11 - 1.17 ) . Intake of vitamin C , beta carotene , and vitamin E from supplements was not significantly associated with risk of AD . CONCLUSION This study suggests that vitamin E from food , but not other antioxidants , may be associated with a reduced risk of AD . Unexpectedly , this association was observed only among individuals without the APOE epsilon 4 allele Physical activity may help preserve cognitive function and decrease dementia risk , but epidemiologic findings are inconsistent . The authors conducted a prospect i ve study to determine the association between physical activity and risk of dementia , Alzheimer 's disease , and vascular dementia . The US study population comprised 3,375 men and women aged 65 years or older , free of dementia at baseline , who participated in the Cardiovascular Health Cognition Study in 1992 - 2000 . Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated . Analyses were based on Cox proportional hazards models . There were 480 incident cases of dementia over an average of 5.4 years of follow-up . After multivariate adjustment , participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 ( 95 % confidence interval : 0.61 , 1.19 ) compared with those in the lowest quartile , and participants engaging in > or=4 activities had a relative risk of dementia of 0.51 ( 95 % confidence interval : 0.33 , 0.79 ) compared with those engaging in 0 - 1 activity . These associations were more marked in apolipoprotein E genotype ( APOE ) epsilon4 allele noncarriers but were absent in carriers . A similar pattern was observed for Alzheimer 's disease and vascular dementia . Mechanisms to explain the observed relations deserve further study OBJECTIVES This study prospect ively describes the relationships between alcohol intake and subsequent cognitive performance among participants in the Honolulu Heart Program ( HHP ) . METHODS Alcohol intake was assessed at Exam III of the HHP , and cognitive performance was measured approximately 18 years later with the Cognitive Abilities Screening Instrument ( CASI ) . Complete information was available for 3556 participants , aged 71 to 93 years at follow-up . RESULTS In multivariate analyses , the relationship between drinking and later cognitive performance appeared nonlinear , as nondrinkers and heavy drinkers ( more than 60 ounces of alcohol per month ) had the lowest CASI scores and the highest risks of poor and intermediate CASI outcomes . Compared with nondrinkers , the risk of a poor CASI score was lowered by 22 % to 40 % among men who consumed 1 - 60 ounces of alcohol per month . CONCLUSIONS We report a positive association between moderate alcohol intake among middle-aged men and subsequent cognitive performance in later life . However , it is possible that the health risks associated with drinking outweight any potential benefits for many elderly persons BACKGROUND Studies relating adiposity to dementia are conflicting . We explored the associations of body mass index ( BMI ) , ( calculated as weight in kilograms divided by the square of height in meters ) waist circumference , and weight change to dementia , probable Alzheimer disease , and dementia associated with stroke ( DAS ) . DESIGN Persons without dementia were followed up for 5 years ; 893 persons had BMI data , 907 had waist circumference data , and 709 had a second weight measurement . Dementia was ascertained using st and ard methods . Cox proportional hazards regression was used for analyses using follow-up as time to event , adjusting for demographics and apolipoprotein E-epsilon4 status . RESULTS Compared with persons in the first quartile of BMI , persons in the third quartile had a lower dementia and Alzheimer disease risk and persons in the second quartile had a lower DAS risk . The association between BMI and dementia resembled a U shape in those younger than 76 years , while dementia risk decreased with higher BMI in those 76 years and older . The fourth quartile of waist circumference was related to a higher DAS risk in the whole sample , and to dementia and Alzheimer disease in persons younger than 76 years . Weight loss was related to a higher dementia and DAS risk , and weight gain was related to a higher DAS risk only . CONCLUSIONS The prospect i ve association between adiposity and dementia differs depending on the anthropometric measure used , and is modified by age . This may explain previous conflicting reports BACKGROUND The association between depressive disorders and subsequent cognitive decline is controversial . We tested the hypothesis that elderly women ( aged 65 years and older ) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms . METHODS As part of an ongoing prospect i ve study , we evaluated 5781 elderly , mostly white , community-dwelling women . Women completed the Geriatric Depression Scale short form . Three cognitive tests -- Trails B , Digit Symbol , and a modified Mini-Mental State Examination -- were administered at baseline and approximately 4 years later . Baseline , follow-up , and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis ; the odds of cognitive deterioration ( > or = 3-point decline on the modified Mini-Mental State Examination ) were determined by logistic regression . RESULTS At baseline , 211 ( 3.6 % ) of the women had 6 or more depressive symptoms . Only 16 ( 7.6 % ) of these women were receiving antidepressant medication . Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function ( P<.001 for all comparisons ) . For example , the baseline Digit Symbol score ( mean + /- SD ) was 45.5 + /- 10.7 among women with 0 to 2 symptoms of depression , 40.3 + /- 10.7 for women with 3 to 5 symptoms , and 39.0 + /- 11.3 for women with 6 or more symptoms . After adjusting for the baseline score , cognitive change scores were also inversely associated with the number of depressive symptoms ( P<.001 for all comparisons ) . Odds ratios for cognitive deterioration using 0 to 2 symptoms as the reference were 1.6 ( 95 % confidence interval , 1.3 - 2.1 ) for 3 to 5 symptoms and 2.3 ( 95 % confidence interval , 1.6 - 3.3 ) for 6 or more symptoms . Results were similar after being adjusted for education , age , health status , exercise , alcohol use , functional status , and clinic site . CONCLUSIONS Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline . Mechanisms underlying the association between these 2 common conditions need further exploration BACKGROUND We report the outcome of depressive states after 3 - 4 years in a community sample of the elderly . METHODS A sample of 1045 persons aged 70 + years in 1990 - 1 was re-interviewed after 3.6 years . RESULTS Mortality ( 21.7 % ) and refusal or non-availability ( 10.4 % ) were higher in those who initially had had a diagnosis or symptoms of depression . Of those with an ICD-10 depressive episode in 1990 - 1 , 13 % retained that diagnosis . Of those who were not depressed initially only 2.5 % had become cases . Depression was unrelated to age or apolipoprotein E genotype . The best predictors of the number of depressive symptoms at follow-up was the number at Wave 1 , followed by deterioration in health and in activities of daily living , high neuroticism , poor current health , poor social support , low current activity levels and high service use . Depressive symptoms at Wave 1 did not predict subsequent cognitive decline or dementia . CONCLUSIONS Non-r and om sample attrition is unavoidable . ICD-10 criteria yield more cases than other systems , while continuous measures of symptoms confer analytical advantages . Risk factors for depressive states in the elderly have been further identified . The prognosis for these states is favourable . At the community level , depressive symptoms do not seem to predict cognitive decline , as they do in referred series Background / Aims : Obesity has a strong association with vascular and metabolic diseases , which have been linked with Alzheimer disease ( AD ) . While recent studies have reported an association between mid-life obesity and dementia , the role of later-life obesity is less clear . This study investigated the relation between AD , obesity and abdominal obesity at later-life in a case-control study . Methods : Participants were 50 consecutive patients with probable AD from memory disorders clinics in Launceston , Australia , and Bristol , Engl and , and 75 cognitively normal controls . Height and weight [ from which body mass index ( BMI ) was calculated ] and hip and waist circumferences ( from which waist-hip ratio was calculated ) were measured . Participants were classified according to their BMI as : underweight ( BMI < 20.0 kg/m2 ) ; normal weight ( BMI 20.0–24.9 kg/m2 ) ; overweight ( BMI 25–29.9 kg/m2 ) , or obese ( BMI ≧30 kg/m2 ) . They were classified as abdominally obese if their waist-hip ratio was > 0.9 ( men ) or > 0.8 ( women ) . Results : AD was associated with obesity [ OR 9.5 , 95 % CI 2.4–37.3 , p = 0.001 ] , underweight ( OR 5.4 , CI 0.9–33.7 , p = 0.07 ) and abdominal obesity ( OR 2.5 , CI 1.1–5.7 , p = 0.027 ) using logistic regression analyses adjusted for age , sex and location . The inclusion of metabolic risk factors in the model increased the ORs for obesity ( OR 12.6 , CI 2.8–56.5 , p = 0.001 ) and underweight ( OR 7.9 , CI 1.0–66.3 , p = 0.056 ) . Conclusion : AD may be associated with obesity , underweight and abdominal obesity at later life . Larger prospect i ve studies are required to investigate this further CONTEXT Previous studies raise the possibility that blood pressure ( BP ) in middle age predicts later cognitive decline . OBJECTIVE To examine prospect ively the relationship of BP with level of and change in cognitive function in the elderly . DESIGN Longitudinal , population -based study comprising subjects enrolled in the East Boston component of the Established Population s for the Epidemiologic Study of the Elderly ( EPESE ) ( 1982 - 1983 ) and the Hypertension Detection and Follow-Up Program ( HDFP ) ( 1973 - 1974 ) . SETTING East Boston , Mass. PARTICIPANTS Of the 3657 participants in the EPESE with baseline BP measurements , 2068 also participated in the HDFP . Subjects were aged 65 to 102 years at baseline in the EPESE and had mental status and memory assessed at baseline and 3 and 6 years . MAIN OUTCOME MEASURES Numbers of errors on the Short Portable Mental Status Question naire and the East Boston Memory Test and rates of change in these numbers of errors . Subjects had BP measured both at baseline in the EPESE and 9 years before , as part of the HDFP . RESULTS In analyses adjusted for age , sex , and education , there was no strong linear association between BP and cognition . The associations found were fairly small in magnitude , and varied according to which test was used to measure cognition . There was little evidence for an effect of BP on change in cognitive function with either test , or for an effect on level of function on the memory test . In analyses of level of mental status question naire performance , however , elevated systolic BP ( > or = 160 mm Hg ) 9 years before baseline was associated with a 14 % ( 95 % confidence interval [ CI ] , 4%-25 % ) increase in error rate , relative to the referent ( 130 - 139 mm Hg ) . Baseline systolic BP had a U-shaped association with the number of errors ; error rates were 9 % higher compared with the referent group among those with systolic BP lower than 130 mm Hg ( 95 % CI , 1%-17 % ) and 7 % greater ( 95 % CI , 0%-15 % ) among those with elevated systolic BP . Diastolic BP 9 years before baseline also had a U-shaped association with errors on the mental status question naire . CONCLUSION The findings do not suggest a linear association of BP with cognitive decline , but they are consistent with a more complex relationship between BP and cognition than previously appreciated Objective : To examine the association of change in body mass index ( BMI ) with risk of Alzheimer disease ( AD ) . Methods : Nine hundred eighteen older Catholic clergy participating in the Religious Orders Study without dementia at baseline were studied . Outcome measures were the clinical diagnosis of AD and change in cognitive function . Results : During a mean follow-up of 5.5 years , 151 persons developed AD . BMI averaged 27.4 at baseline and declined in about half the participants . In a proportional hazards model adjusted for age , sex , and education , each 1-unit less of BMI at baseline was associated with about a 5 % increase in the risk of AD ( hazard ratio = 0.944 ; 95 % CI = 0.908 to 0.981 ) , and each 1-unit annual decline in BMI ( about the 10th percentile ) was associated with about a 35 % increase in the risk of AD compared with a person experiencing no change in BMI ( about the 50th percentile ) ( hazard ratio = 0.730 ; 95 % CI = 0.625 to 0.852 ) . The results were similar after controlling for chronic diseases and excluding persons who developed AD during the first 4 years of observation . R and om effects models showed that the rate of cognitive decline increased by about 8 % for each 1-unit less of BMI at baseline and declined an additional 40%/year in persons losing 1 unit of BMI /year compared with those with no change in BMI . Conclusion : Declining body mass index ( BMI ) is associated with increased risk of incident Alzheimer disease ( AD ) . Loss of BMI may reflect pathologic processes that contribute to the subsequent development of AD BACKGROUND Vascular risk factors play a role in the development of dementia , including Alzheimer disease ( AD ) . However , little is known about the effect of body mass index and clustering of vascular risk factors on the development of dementia . OBJECTIVE To investigate the relation between midlife body mass index and clustering of vascular risk factors and subsequent dementia and AD . DESIGN AND SETTING Participants of the Cardiovascular Risk Factors , Aging , and Dementia ( CAIDE ) study were derived from r and om , population -based sample s previously studied in a survey carried out in 1972 , 1977 , 1982 , or 1987 . After an average follow-up of 21 years , 1449 individuals ( 73 % ) aged 65 to 79 years participated in the reexamination in 1998 . MAIN OUTCOME MEASURES Dementia and AD . RESULTS Obesity at midlife ( body mass index>30 kg/m2 ) was associated with the risk of dementia and AD even after adjusting for sociodemographic variables ( odds ratio [ OR ] , 2.4 [ 95 % confidence interval ( CI ) , 1.2 - 5.1 ] ) . The association was somewhat modified by further adjusting for midlife blood pressure , total cholesterol level , and smoking ( OR , 2.1 [ 95 % CI , 1.0 - 4.6 ] ) and also for apolipoprotein E genotype and history of vascular disorders ( OR , 1.9 [ 95 % CI , 0.8 - 4.6 ] ) . Midlife obesity , high total cholesterol level , and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each factor , and they increased the risk additively ( OR , 6.2 for the combination ) . CONCLUSIONS Obesity at midlife is associated with an increased risk of dementia and AD later in life . Clustering of vascular risk factors increases the risk in an additive manner . The role of weight reduction for the prevention of dementia needs to be further investigated Background : Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD , but there have been few prospect i ve studies and their results have been inconsistent . Methods : Participants are Catholic clergy members who were aged ≥65 years and who did not have clinical evidence of AD . During a 7-year period , they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived . Number of depressive symptoms was assessed at baseline with a modified , 10-item Center for Epidemiologic Studies Depression Scale ( CES-D ) . The association of CES-D score with incident AD , using proportional hazards models , and cognitive decline , using r and om effects models , was examined . Results : At baseline , participants reported an average of about one depressive symptom on the CES-D scale ( range , 0 to 8) . During the 7 years of follow-up , 108 persons developed AD . In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function , CES-D score was associated with both risk of AD and rate of cognitive decline . For each depressive symptom , risk of developing AD increased by an average of 19 % , and annual decline on a global cognitive measure increased by an average of 24 % . Conclusions : The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD Moderate levels of alcohol intake may be associated with better cognitive function ; however , this relationship may vary between cognitive domains . Women , aged 65–80 years , enrolled in the Women ’s Health Initiative ( WHI ) r and omized clinical trials of hormone therapy , underwent annual st and ardized testing for global cognitive function through the ancillary WHI Memory Study ( average follow-up of 4.5 years ) and domain-specific cognitive function through the WHI Study of Cognitive Aging ( average follow-up of 1.7 years ) . Compared to nondrinkers , women reporting moderate levels of alcohol intake ( ≤3 drinks per day ) performed better on a measure of global cognitive function . Women reporting any alcohol intake also performed better on tests of verbal knowledge , verbal fluency , figural memory , verbal memory , attention and working memory , and motor speed ( all p < 0.05 ) , but not spatial ability ( p = 0.36 ) . After covariate adjustment , mean scores were higher among women reporting ≧1 drink/day by 5.7 % for verbal knowledge ( p < 0.001 ) and by 5.7 % for phonemic fluency ( p = 0.004 ) , compared to never-drinkers . Moderate levels of alcohol intake are associated with somewhat better cognition , which may be expressed most strongly in functions related to verbal knowledge and phonemic fluency . However , our observational study can not rule out confounding associations with unmeasured factors Among neurologically normal volunteers approaching age 65 with an option for retirement , a four-year prospect i ve longitudinal study was design ed to examine effects of different levels of physical activity on cerebral perfusion by between-group comparisons . After the fourth year , cognitive performance was also tested . Three groups were compared , each composed of 30 elderly volunteers , assigned as follows : Group 1 , who continued to work ; Group 2 , who retired but participated in regular physical activities ; and Group 3 , who retired but did not participate in regular , planned physical activities . Retirees who elected to become physically inactive exhibited significant declines in cerebral blood flow ( CBF ) throughout four years of follow-up . Those who continued to work or retirees who elected to participate in regular activities sustained more constant CBF levels . Active retirees and those who continued to work also scored better on cognitive testing after the fourth year of follow-up compared to inactive retirees BACKGROUND Several studies have suggested that physical activity is positively associated with cognitive function in elderly persons . Evidence about this association has been limited by the cross-sectional design of most studies and by the frequent lack of adjustment for potential confounding variables . We determined whether physical activity is associated with cognitive decline in a prospect i ve study of older women . METHODS We studied 5925 predominantly white community-dwelling women ( aged > or = 65 years ) who were recruited at 4 clinical centers and were without baseline cognitive impairment or physical limitations . We measured cognitive performance using a modified Mini-Mental State Examination at baseline and 6 to 8 years later . Physical activity was measured by self-reported blocks ( 1 block approximately 160 m ) walked per week and by total kilocalories ( energy ) expended per week in recreation , blocks walked , and stairs climbed . Cognitive decline was defined as a 3-point decline or greater on repeated modified Mini-Mental State Examination . RESULTS Women with a greater physical activity level at baseline were less likely to experience cognitive decline during the 6 to 8 years of follow-up : cognitive decline occurred in 17 % , 18 % , 22 % , and 24 % of those in the highest , third , second , and lowest quartile of blocks walked per week ( P < .001 for trend ) . Almost identical results were obtained by quartile of total kilocalories expended per week . After adjustment for age , educational level , comorbid conditions , smoking status , estrogen use , and functional limitation , women in the highest quartile remained less likely than women in the lowest quartile to develop cognitive decline ( for blocks walked : odds ratio , 0.66 [ 95 % confidence interval , 0.54 - 0.82 ] ; for total kilocalories : odds ratio , 0.74 [ 95 % confidence interval , 0.60 - 0.90 ] ) . CONCLUSIONS Women with higher levels of baseline physical activity were less likely to develop cognitive decline . This association was not explained by differences in baseline function or health status . This finding supports the hypothesis that physical activity prevents cognitive decline in older community-dwelling women This study aims to describe factors associated with cognitive decline among 2584 subjects , aged 65 - 74 , who were followed up for 54 months in the Medical Research Council Elderly Hypertension Trial ( 1982 - 1989 ) . The subjects completed a cognitive test , the Paired Associate Learning Test ( PALT ) , five times over this period . Decline on the PALT was associated with advanced age , male sex , rural residence , depression and low intelligence . These effects were modified by gender and level of pre-morbid intelligence . Advanced age , rural residence and number of cigarettes smoked daily were only associated with PALT decline among women of below median intelligence . The association between depression and PALT decline was only apparent in women of below median intelligence and men of above median intelligence . While these findings are consistent with other research into cognitive decline , they differ in some ways from reported risk factors for dementia , suggesting aetiological separateness . That women were more vulnerable than men to the effects of age and smoking raises the question of the impact on cognition of accelerated atherosclerosis after the menopause BACKGROUND Previous studies have shown that risk factors commonly associated with coronary disease , stroke , and other vascular disorders also predict dementia . We investigated the longitudinal relationship between body mass index ( BMI , calculated as weight in kilograms divided by the square of height in meters ) and risk of hospital discharge or death certificate diagnosis of dementia . METHODS A total of 7402 men who were 47 to 55 years old in 1970 to 1973 , without prior stroke or myocardial infa rct ion , derived from a population sample of 9998 men were prospect ively followed up until 1998 . Two hundred fifty-four men ( 3.4 % ) had a hospital discharge diagnosis or a death certificate diagnosis of dementia : 176 with a primary diagnosis or cause of death and 78 with a secondary diagnosis . RESULTS The relationship between BMI and dementia as a primary diagnosis was J-shaped , and men with a BMI between 20.00 and 22.49 had the lowest risk . Subsequently , after adjustment for smoking , blood pressure , serum cholesterol level , diabetes mellitus , and social class , the risk increased linearly in men who had a BMI of 22.50 to 24.99 ( multiple-adjusted hazard ratio [ HR ] , 1.73 ; 95 % confidence interval [ CI ] , 0.92 - 3.25 ) , 25.00 to 27.49 ( HR , 1.93 ; 95 % CI , 1.03 - 3.63 ) , 27.50 to 29.99 ( HR , 2.30 ; 95 % CI , 1.18 - 4.47 ) , and 30.00 or greater ( HR , 2.54 ; 95 % CI , 1.20 - 5.36 ) ( P for linear trend = .03 ) . Men with a BMI less than 20.00 had a nonsignificantly elevated risk ( HR , 2.19 ; 95 % CI , 0.77 - 6.25 ) . CONCLUSIONS A J-shaped relationship was observed between BMI and dementia , such that a BMI less than 20 and an increasing BMI of 22.5 or greater were associated with increased risk from midlife to old age of a primary hospital diagnosis of dementia . Overweight and obesity could be major preventable factors in the development of dementia Abstract .The etiology of weight loss in Alzheimer ’s disease ( AD ) patients is still uncertain . This study was design ed to investigate the possible factors that might contribute to weight change of AD patients . From July 1999 to June 2001 , we recruited 51 AD patients and 27 non-demented controls . Demographic data , neuropsychological tests , Geriatric Depression Scale-Short Form , eating behavior question naire , dietary and physical activity diaries , anthropometric and laboratory measures of nutritional status were assessed . More than half of our AD patients developed body weight loss , and overall , the AD patients were significantly thinner than the non-demented subjects . Anthropometric and laboratory measures suggested a poorer nutritional status in the AD patients . The AD patients had fewer daily physical activities . More AD patients had the problem of poor appetite . However , daily calorie intake was not significantly different between the two groups . The AD patients , especially those who presented with body weight loss , even consumed more calories per body weight kilogram ( kg ) per day . In the food composition analysis , AD patients took more carbohydrate than controls . Multivariate regression analysis showed the existence of AD and poor appetite were the main risk factors of weight loss . We suggest that the pathophysiological process in AD gives rise to the changes of appetite and metabolic state in AD patients , and that these changes contribute to the weight loss BACKGROUND The relation between plasma lipid levels and Alzheimer disease ( AD ) and vascular dementia ( VaD ) , and the impact of drugs to lower lipid levels remains unclear . OBJECTIVE To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship . DESIGN AND SETTING Cross-sectional and prospect i ve community-based cohort studies . PARTICIPANTS R and om sample of 4316 Medicare recipients , 65 years and older , residing in northern Manhattan , NY . MAIN OUTCOME MEASURES Vascular dementia and AD according to st and ard criteria . RESULTS Elevated levels of non-high-density lipoprotein ( HDL-C ) and low-density lipoprotein cholesterol ( LDL-C ) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospect i ve analyses . Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics , apolipoprotein E genotype , and cardiovascular risk factors . Treatment with drugs to lower lipid levels did not change the disease risk of either disorder . CONCLUSIONS We found a weak relation between non-HDL-C , LDL-C , and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD Growing evidence suggests that physical exercise may be protective against cognitive impairment and decline . A prospect i ve study of a representative rural community sample ( N = 1,146 ) aged 65 + years examined self-reported exercise habits and measured global cognitive function using the Mini-Mental State Examination ( MMSE ) . A composite variable “ exercise level ” combining type , frequency , and duration of exercise was created with three levels : “ high exercise ” ( aerobic exercise of ≥ 30 minute duration ≥ 3 times a week ) , “ low exercise ” ( all other exercise groups ) , and “ no exercise . ” Cognitive decline was defined as being in the 90th percentile of decline in this cohort , ie , declining by 3 or more MMSE points during the 2-year interval between two assessment s. In a multiple regression model , high exercise level at the baseline assessment was negatively associated with , ie , was protective against , being in the group with the greatest amount of decline at the follow-up assessment , after adjusting for likely confounders ( odds ratio = 0.39 ; 95 % confidence interval , 0.19 , 0.78 ) . When high exercise was redefined using frequency as ≥ 5 days per week as the threshold , as per the Surgeon General ’s guidelines , both low exercise and high exercise were negatively associated with cognitive decline . Exercise may have implication s for prevention of cognitive decline Objective : To investigate the association between diabetes and impaired fasting glucose ( IFG ) and cognition and risk of developing both dementia and mild cognitive impairment ( MCI ) in older women . Methods : The authors analyzed data from a 4-year r and omized trial of raloxifene among 7,027 osteoporotic postmenopausal women ( mean age , 66.3 years ) at 178 sites . Diabetes was defined by history , fasting blood glucose ≥7.0 mmol/L ( ≥126 mg/dL ) , or use of hypoglycemic agents ; IFG was defined as fasting glucose < 7.0 mmol/L but > 6.11 mmol/L ( 110 mg/dL ) ; all others were considered to have normal glucose ( NG ) . The main outcome was baseline and 4-year change on five st and ardized cognitive tests ( z scores with lower scores indicating worse performance ) and risk of developing clinical ly significant impairment ( dementia , mild cognitive impairment , or very low cognitive score ) . Results : A total of 267 ( 3.8 % ) women had diabetes and 297 ( 4.2 % ) had IFG . Women with IFG had worse baseline cognitive scores compared to women with NG but better scores than diabetics ( age-adjusted composite z score based on five tests : NG 0.40 , 95 % CI 0.30 to 0.49 ; IFG 0.14 , 95 % CI −0.36 to 0.64 ; diabetics −0.78 , 95 % CI −1.23 to −0.33 ; p < 0.001 ) . There was greater 4-year decline among diabetics ( age and treatment-adjusted composite z score : NG −0.05 , 95 % CI −0.16 to 0.05 ; IFG 0.11 , 95 % CI −0.53 to 0.75 ; diabetics −1.00 , 95 % CI −1.50 to −0.50 ; p = 0.001 ) . Further adjustment for education , race , and depression led to similar results . Risk of developing cognitive impairment among women with IFG or diabetes was increased by almost twofold ( age and treatment-adjusted OR = 1.64 ; 95 % CI 1.03 to 2.61 for IFG ; OR = 1.79 ; 95 % CI 1.14 to 2.81 for diabetics ) . Conclusions : Diabetic as well as pre-diabetic women have impaired cognitive performance and greater risk of developing cognitive impairment |
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